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German Center for Infection Research
ANNUAL REPORT
2014
Title: A hepatitis C virus finds its way into a liver cell using different adhesion and receptor molecules.
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DZIF at a glance
The German Center for Infection Research (DZIF) coordinates and oversees
the strategic planning of translational infection research within Germany.
Its mission is to translate the results from basic biomedical research into
clinical research.
35 DZIF research centres work concertedly against the global threat
presented by infectious diseases.
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Table of contents
Editorial ..................................................................................................................................................................................................................... 3
About DZIF ............................................................................................................................................................................................................ 4
Science - Translation in focus
Emerging infections . ........................................................................................................................................................................... 6
Tuberculosis . ................................................................................................................................................................................................. 8
Malaria . ........................................................................................................................................................................................................... 10
HIV ........................................................................................................................................................................................................................ 12
Hepatitis ......................................................................................................................................................................................................... 14
Gastrointestinal Infections ..................................................................................................................................................... 16
Infections of the immunocompromised Host . ................................................................................................. 18
Healthcare-associated and Antibiotic-resistant bacterial Infections .................................. 20
Novel Antiinfectives . ...................................................................................................................................................................... 22
Research infrastructures
Product Development Unit . .................................................................................................................................................. 24
Clinical Trial Unit . ................................................................................................................................................................................ 25
African Partner Institutions ................................................................................................................................................... 26
Natural Compound Library . .................................................................................................................................................. 27
Biobanking .................................................................................................................................................................................................. 28
Bioinformatics ........................................................................................................................................................................................ 29
DZIF Academy .............................................................................................................................................................................................. 30
Collaborations at the DZIF. ........................................................................................................................................................... 31
DZIF Highlights 2014 . ......................................................................................................................................................................... 32
Science and public .................................................................................................................................................................................... 34
External collaborations ..................................................................................................................................................................... 36
German Health Research Centres ...................................................................................................................................... 39
Facts and figures
Organisation and bodies ............................................................................................................................................................ 40
Partner sites and member establishments .......................................................................................................... 42
Finance . .......................................................................................................................................................................................................... 46
Personnel and awards . ................................................................................................................................................................. 48
Publications ............................................................................................................................................................................................... 50
Member establishments ............................................................................................................................................................ 53
Imprint .................................................................................................................................................................................................................... 54
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Last year again demonstrated the kind of global challenges infection research is confronted with. The unusual
magnitude and spread of the still ongoing Ebola epidemic in West Africa required concerted international action plans
to contain the disease. In September 2014, the WHO declared the Ebola epidemic to be “out of control”.
During this crisis, the DZIF was able to prove its strength: in March 2014, our physicians and scientists from Hamburg,
Marburg and Munich were already on the ground in Africa to establish viral diagnostics and to help the people
affected. Furthermore, a research consortium to tackle Ebola – EBOKON – was established within the shortest time
under the leadership of the DZIF research field “Emerging Infections”, and was generously supported with further
federal funding. A definite highlight was the DZIF’s participation in clinical trials for a vaccine against the Ebola virus
in Hamburg and Lambaréné.
Over the last year, antibiotic-resistant pathogenic bacteria returned to the public spotlight, and the DZIF network
accomplished internationally acknowledged success here as well. With teixobactin and cystobactamides, DZIF
scientists have identified new active agents which have the potential to form a new generation of antibiotics. Product
development now needs to be expedited in collaboration with the industry.
After longstanding research work, the research goals for HIV and viral hepatitis are on the verge of a change of
paradigm: new active agents have made chronic hepatitis C a curable disease. The DZIF partner sites have made
significant contributions to this development and testing. This development raises hopes that other chronic infections
such as hepatitis B and HIV infection may also be cured.
We hope these examples have inspired you to continue reading. The Annual Report illustrates the DZIF’s broad range
of translational research approaches, including the latest diagnosis, prevention and treatment approaches of MERS
coronavirus, HIV, malaria and tuberculosis.
DZIF e.V. Executive Board
Prof Dr Martin Krönke
Prof Dr Ulrike Protzer
Prof Dr Dirk Heinz
EDITORIAL
Editorial
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About DZIF
ABOUT DZIF
A national network for
international infection research
United against infections: group photo at the DZIF Annual Meeting 2014.
Infectious diseases remain a major challenge in medicine, even in the 21st century. How can we stop the
spread of pathogens? Which new treatment approaches work? What should we do when pathogens become insensitive to antibiotics? Researchers at the
German Center for Infection Research (DZIF) try to
answer these questions, and others. They develop
new drugs, vaccines, and preventive measures against
infectious diseases.
The German Center for Infection Research is a research association, organised virtually, with an affiliation
of a total of 35 establishments at seven partner sites.
Around 250 scientists work together across the different partner sites in Germany. Under the motto “United against infections”, they contribute their expertise
to developing new agents against infectious diseases.
DZIF research activities are strategically planned and
aligned to accomplish this from the start.
The DZIF is one of six German Centers for Health Research (DZG) established by the German Federal Ministry of Education and Research (BMBF). The fundamental
goal of this initiative is to fight widespread diseases more
effectively. The DZIF started its work under the umbrella
of this alliance in 2012. Financing is 90 percent from federal funds and 10 percent from participating federal states´
funds.
Organised across the sites
All researchers have the infrastructures and competencies of the existing establishments at their disposal.
DZIF partner sites include: Bonn-Cologne, GießenMarburg-Langen, Hamburg-Lübeck-Borstel, Hannover-
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Aligning translation
The DZIF aims to close existing gaps between basic research and clinical applications. Research is governed by
the practical needs of the patient. To this effect, the DZIF
promotes a rapid transfer of research results from bench
to bedside (translation). Well-structured collaboration between researchers, medical doctors, probands and patients
ensures smooth operating procedures. In doing so, patients
benefit faster from the improvements made to diagnosis,
prophylaxis and treatment of infectious diseases.
Structured thematically
The DZIF is divided into nine research fields. In each field,
specialised scientists at the different partner sites dedicate themselves to working on a pathogen or specific
issue in infection research. The research fields are called
“Emerging Infections”, “Tuberculosis”, “Malaria”, “HIV”,
“Hepatitis”, “Gastrointestinal Infections”, “Infections of
the immunocompromised Host”, “Healthcare-associated
and Antibiotic-resistant bacterial Infections”, and “Novel
Antiinfectives”.
Supportive infrastructure
Moreover, the DZIF has established its own infrastructures important to its research. These comprise specialised
services which are available to all members and provide
support. Here, for example, information is collected for
subsequent processing, and important patient samples or
natural substances are stored for later testing. Advice is
provided for difficult processes, and further training for
next-generation talents. Also, contacts can be made to
establishments all over the world.
Collaborating internationally
Numerous collaborations with external scientific institutions and the industry strengthen the DZIF’s position
as a top-class institution for infection research. In addition,
it has international partner sites, for example in Africa and
Eastern Europe. In this way, infectious diseases which are
rare in Germany, such as malaria, Ebola and tuberculosis,
can be researched where they occur frequently. These
contacts and collaborations are critical to the DZIF for taking on the global challenges in infection research.
DZIF groups its research activities into nine research fields and six research infrastructures –
internally called Thematic Translational Units (TTUs)
and Translational Infrastructures (TIs):
Research fields
• Emerging Infections
• Tuberculosis
• Malaria
• HIV
• Hepatitis
• Gastrointestinal Infections
• Infections of the immunocompromised Host
• Healthcare-associated and Antibiotic-resistant
bacterial Infections
• Novel Antiinfectives
Research infrastructures
• Product Development Unit
• Clinical Trial Unit
• African Partner Institutions
• Natural Compound Library
• Biobanking
• Bioinformatics
• DZIF Academy
ABOUT DZIF
Braunschweig, Heidelberg, Munich und Tübingen. DZIF
research institutes, universities, hospitals and federal
research institutes collaborate across the sites. Basic research, epidemiology and clinical research are promoted
equally.
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Emerging Infections
SCIENCE – TRANSLATION IN FOCUS
Reacting rapidly to unexpected
strangers
“We have survived”: An impressive thank you to all Ebola helpers on the ground, including those from the DZIF.
Numerous new pathogens have emerged over the
last 40 years, causing diseases such as AIDS, avian influenza and Ebola. In the era of global mobility, viruses
and bacteria also know no boundaries. For this reason,
DZIF researchers in the field “Emerging Infections” often
have to react swiftly to stop the spread of unknown
pathogens. In order to achieve this, scientists from research institutes, hospitals and public health services
work closely together.
DZIF researchers focus on characterising pathogens rapidly, developing new drugs and vaccines, as well as epidemiological investigations. The reason for this is that emerging
infectious diseases, like Ebola, can be curbed more effectively, the earlier the pathogen and its routes of spread are
identified. On several occasions, DZIF researchers discovered that some pathogens are transmitted from animals to
humans. Avian influenza and Ebola belong to this group of
pathogens. They cause diseases termed zoonoses and are
responsible for around three quarters of all emerging infections. They often originate from viruses that have been
transmitted from wild animals to humans.
Better prepared for unexpected outbreaks
In this context, DZIF scientists investigated the evolutionary biology of the hepatitis C virus which causes severe
inflammation of the liver in humans. “We want to understand where the hepatitis C virus comes from,” explains
Prof Jan Felix Drexler from the Institute of Virology of
the University of Bonn. Together with colleagues from
Hamburg, Hannover, Ghana and Moscow, his team recently discovered novel viruses that are distantly related to
the hepatitis C virus. The researchers found them in cattle
which they investigated at the DZIF partner institution in
in Switzerland, Gabon and Kenya, researchers concurrently tested a vaccine called “rVSV-ZEBOV” in a total of
158 healthy adults. “The preliminary results on tolerability and safety, as well as the immune response, are promising,” explains DZIF researcher Prof Marylyn Addo,
who is leading the trial at the UKE. “The data from this
trial are very helpful for further clinical trials, for example on people who have been in contact with Ebola in Guinea, and they have also helped determine the dosage.”
Other projects in the research field include epidemioIn Ghanaian cattle, researchers discovered new viruses that are
logical studies on origin, transmission and spread of
distantly related to hepatitis C viruses.
the MERS coronavirus. The virus, which up to now has
been predominantly transmitted to humans from camels, leads to severe respiratory illness, the so-called
Ghana. Just like the hepatitis C virus, these newly discovMiddle East Respiratory Syndrome (MERS). Virologists
ered novel viruses belong to the group of hepaciviruses.
fear that the virus may alter and subsequently transmit
However, Drexler is certain,
more easily from humans to
“The Ebola trial was a networking success. humans—which could result
no person with hepatitis C
infection contracted the viin larger epidemics. For this
We would not have made it without
rus from cows—the genetic
reason, DZIF researchers
the other colleagues, the DZIF and
differences are too large.
are working intensively on
international
networking.”
Nevertheless, this discovery
further investigating and
Prof Dr Marylyn Addo, Head of Infectiology Section, Department of
allows for important insights
introducing a vaccine.
Internal Medicine I, at the University Medical Center Hamburg-Eppendorf
into the evolution of hepaciviruses. In general: “Only
when you know whether a human virus actually originaCoordinator:
ted from animals, can you react to future outbreaks and
Prof Dr Stephan Becker
work towards eradicating certain viruses,” says Drexler.
Marburg
Ebola virus epidemic: rapid reaction in emergencies
The Ebola virus, first described in 1976, could be contained quickly with quarantine measures in all previous
outbreaks. However, the 2014 epidemic in West Africa,
reached unforeseen dimensions of cases and deaths. Researchers worldwide searched for ways to fight the epidemic, in which patients presented symptoms of fever,
vomiting, diarrhoea and internal bleeding, often ending
in death. An international expert consortium, led by the
WHO, selected a promising candidate vaccine on which
to conduct further trials. DZIF researchers were also
involved with the first clinical trial in humans. At the
University Medical Center Hamburg-Eppendorf (UKE),
SCIENCE – TRANSLATION IN FOCUS
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Tuberculosis
SCIENCE – TRANSLATION IN FOCUS
Modern approaches to f ighting an
ancient epidemic
Tuberculosis (TB) has become rare in Germany.
However, it is a major global public health problem:
nine million people contract TB every year; 1.5 million die from the disease. The TB pathogen, the socalled tubercle bacillus, typically infects the lungs
and spreads to other organs. DZIF scientists in the
research field “Tuberculosis” investigate new methods for prevention and diagnosis. Furthermore,
they participate in developing and testing new
active substances against TB.
resistant (MDR) clones of this particular strain. The
Beijing strains originated over six thousand years ago.
The strains probably spread from Eastern China to
Europe via the Silk Road, and by ship. Towards the end of
the 19th century, they spread into Russian Republics
and into the Pacific region during surges of migration.
Soldiers, refugees and famine during the First World
War accelerated the spread. One remarkable finding
was that current high rates of MDR TB in Eastern
Europe are mainly due to two main outbreak strains.
Beneficial genetic mutations in the bacteria are most
At the partner sites Hamburg-Lübeck-Borstel,
likely the reason for their efficient transmission and
Hannover-Braunschweig, Munich and Tübingen, DZIF
extreme spread over the last 20 years. “Amongst
scientists link basic research with clinical applications
other things, this study also highlights the imporin Germany. Beyond this, together with 600 colleagues
tance of efficient tuberculosis surveillance and rapid
from the European research
identification of antibiotic
“The DZIF bridges the gap between
network TBNET, they are
resistance with molecular
challenged with a global
methods,” explains Prof
research and patient care.”
problem: there is no effecStefan Niemann, Head of
Prof Dr Christoph Lange, Head of Clinical Infectious Diseases
tive vaccine against tuberthe study at the Research
at the Medical Clinic of the Research Center Borstel
culosis. Treatment consists
Center Borstel. “Outof several antibiotics and often takes many months. Side
breaks and spread of multidrug-resistant tuberculosis
effects, high treatment costs and a lack of compliance
could then be identified and contained in time.”
often lead to abandonment of treatment. Co-infections
and antibiotic-resistant tubercle bacilli complicate
Reliable diagnostics and tailored
the situation. Researchers are particularly concerned
therapy required
about the rapid increase of multidrug-resistant and
Countries with high TB rates often do not have the reextensively drug-resistant TB strains (M/XDR tubersources to treat their patients. “It is our human duty to
culosis), for which patients seldomly receive effective
take care of the patients in these countries,” says Prof
treatment.
Christoph Lange, Head of Clinical Infectious Diseases
in Borstel. In a TBNET trial, DZIF researchers concenTracing and tracking multidrug-resistant pathogens
trated on TB infected patients who had weak immune
around the world
systems due to pre-existing illnesses. These patients
Multidrug-resistant TB strains are spreading, esperun a high risk of developing tuberculosis disease. Here,
cially in Eastern Europe, Africa and Asia. DZIF scienthe researchers tested the reliability of TB tests: they
tists are doing genuine detective work to stop their
compared two, WHO-recommended rapid molecular
spread and to trace the evolutionary history of tudiagnostic tests to the conventional tuberculin test.
bercle bacilli. In a consortium consisting of 55 TB reEspecially patients with HIV infections developed TB
searchers, they analysed genetic fingerprints of almost
symptoms whereby the rapid molecular tests did not
5,000 tuberculosis strains of the so-called Beijing
confirm all cases. Patients with weak immune systems
lineage, from 99 countries. With this study, they could,
who received preventive antibiotic treatment during
for the first time, show the global spread of multidrugthe study did not develop symptoms. “This result shows
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SCIENCE – TRANSLATION IN FOCUS
Tuberculosis strains of the Beijing genotype have spread globally
along historical trade routes. Photo: courtesy of: Merker et al,
NatGen 47, 242–249 (2015); doi: 10.1038/ng.3195
Not without a face mask: tuberculosis bacteria are transmitted by coughing and sneezing.
that we have to redefine risk groups and use preventive
therapy to contain the spread,” says Lange. Overall, the
DZIF scientists are therefore increasingly focussing on
concepts of tailoring treatment to adjust it to antimicrobial resistance and pre-existing illness.
Beyond this, the DZIF is also active in endemic areas.
For example, it is funding the establishment of a new
trial centre in Bucharest, Romania. Here, new drugs
are to be tested in the largest EU tuberculosis hospital. Additionally, a consultation service for doctors has
been established, where DZIF infectious diseases specialists are available around the clock to give competent
advice. In a national online teleconference, the doctors
and scientists discuss best case management of MDRTB patients with competent colleagues from other sites
in Germany. In a national TB cohort, DZIF researchers
are investigating biomarkers for individualising therapy.
Coordinator:
Prof Dr Stefan Niemann
Borstel
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Malaria
SCIENCE – TRANSLATION IN FOCUS
Fighting against intermittent
fever
The DZIF is working closely with African partner institutions to fight malaria.
Every year, there are approximately 200 million cases
Despite extensive research, the fight against malaria
of malaria and 600,000 malaria deaths; 90 percent of
has been challenging scientists all over the world: rewhich occur in Africa. Children under five years are
gional genetic differences in the pathogen and in
particularly vulnerable, where the infection is one of
populations complicate treatment. Further obstacles
the major causes of death.
are co-infections with other
Parasites, so-called plas- “The DZIF’s collaborations and support have pathogens and resistance
modia, cause this tropical
made it possible to bridge the gap between to conventional treatment.
disease which is transmitConsequently, researchers
basic research and clinical research.”
ted through mosquitos.
have to constantly adTypically, the disease prejust their interventions to
PD Dr Benjamin Mordmüller, Institute for Tropical Medicine
at the University of Tübingen
sents with intermittent
fight this highly adaptable
phases of fever. DZIF repathogen. The DZIF scisearchers in Tübingen, Heidelberg and Hamburg foentists are therefore also looking for alternative pathcus on developing new methods of prevention and
ways. The main areas of focus in the research field
therapy, as well as epidemiological measures to fight
“Malaria” are to test and optimise alternative methods
the spread of malaria.
of vaccination, and to develop parasite inhibitors.
Furthermore, scientists are investigating the regional
A mosquito-bite can be dangerous if the insect is carrying the
malaria parasite.
spread of the pathogens, in order to effectively plan
malaria interventions in the affected areas. To this
effect, the DZIF is working together closely with African
partner institutions in Ghana, Burkina Faso and Gabon.
Protection against dangerous parasites
Although the quest for a vaccine has been ongoing for
years, only a moderately effective vaccine, at best, will be
available in the near future. At the Institute for Tropical
Medicine of the University of Tübingen, DZIF researchers
are testing a new vaccination method in a clinical trial.
They intravenously inject live plasmodia and simultaneously administer a drug for malaria to weaken them.
This method has been shown to fundamentally work in
animal models, as well as in a clinical trial that used infected mosquitoes instead of the purified plasmodia. It results in effective vaccine protection. “By using the entire
pathogen, we obtain a strong and broad immune response,” says Dr Benjamin Mordmüller at the DZIF partner site Tübingen. “This vaccination method stands good
chances of being approved,” Mordmüller believes. “Then
it can also be used to prevent malaria in children in Africa.”
Fever does not necessarily mean malaria
Especially children are in urgent need of protection against
malaria. In African countries, they frequently suffer from
fever of unclear origin. “Differentiating between malaria
and other infections is hardly possible, given the available
facilities,” explains Prof Jürgen May, Head of the Research
Group on Infectious Disease Epidemiology at the Bernhard Nocht Institute for Tropical Diseases in Hamburg. In
one trial conducted at the African partner institutions, the
DZIF team led by May investigated children with severe
febrile illnesses in hospitals. With the help of conventional methods and molecular diagnostics, they determined
the frequency, risk and treatment options of malaria coinfections. In doing so, they could confirm that the degree of severity of the illness was higher in cases of coinfection. Conversely, malaria also facilitates simultaneous infection with other pathogens, particularly salmonella, as the team from Hamburg observed. “We therefore
want to develop a rapid bedside test,” May explains.
Further projects
In other projects, DZIF researchers are developing novel
parasite inhibitors. Moreover, scientists in Hamburg are
developing mathematical models to describe the regional
spread of the parasites. Models can also help determine
the parasites’ life cycles in infected people’s blood.
Coordinator:
Prof Dr Peter Kremsner
Tübingen
SCIENCE – TRANSLATION IN FOCUS
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HIV
SCIENCE – TRANSLATION IN FOCUS
Luring retroviruses
out of hiding
At the DZIF, Dr Marina Lusic researches HIV’s game of hide-and-seek.
Since its discovery in the year 1983, the human immunodeficiency virus (HIV) has spread worldwide: 35
million people are HIV positive, 1.5 million die every
year from the consequences of HIV infection—the
immune deficiency syndrome AIDS. As yet, there has
been no effective vaccine and no prospect of cure. In
view of this situation, the DZIF research field “HIV”
has set itself the ambitious goal of developing new
treatment methods, with the particular aim of curing
the disease.
HIV belongs to the family of retroviruses: they insert
their genetic information into the host’s genome before becoming active. Of all cells, HIV chooses human immune system cells as its host. Once integrated into the host
genome of these immune cells, the virus’s genes become
insusceptible to attack—by both the human immune
defence system and by drugs, as these only target the free
viruses in the blood. As soon as treatment is omitted, the
virus’s genetic material is reactivated, and the body gets
flooded with viruses once again. Virologists describe this
hide-and-seek game as latency, and consider this to be the
reason why HIV has so far remained incurable.
Discovered in its hiding place
In Heidelberg, DZIF scientist Dr Marina Lusic investigates
HIV latency, in collaboration with colleagues from Cologne
and Hamburg. The virologist is convinced, “Only by understanding the mechanisms of HIV latency will we be able
to develop therapeutic countermeasures.” In 2014, the
young scientist received a tenure-track position funded
by the DZIF, for preclinical HIV research at the University
of Heidelberg. This exemplifies that furthering careers
at the DZIF also plays an important role. The scientist
View of the most delicate structures in the HIV
Photo: courtesy of Macmillan Publishers LTD: from Nature 517,
505–508
hiding place and activated with drugs to subsequently be
destroyed in the blood.” Together with researchers from
the Rockefeller University in New York (USA), DZIF physicians from the University Hospital of Cologne are investigating a new treatment approach. The international team
has tested a new generation of antibodies in humans for
the first time. The trial, also funded by the DZIF, showed:
the antibodies can effectively neutralise a large number
of different HIV viruses and significantly reduce infected
people’s viral loads. “The antibody´s effect proved to be
comparable to the current drugs being used for treatment,” says Fätkenheuer. “This method opens up a new
field of HIV treatment and could, in future, possibly also
be used as a preventive measure after fresh infections. Its
principle is similar to that of a passive vaccination.”
investigated how the virus alters the nucleus and genome
A further DZIF team, led by Prof Joachim Hauber at the
structure of infected cells to suit its purpose. Together
Heinrich-Pette Institute in Hamburg builds on a gene therwith her team in the Department of Infectious Diseases
apy approach: developing new specific enzymes that are
at the Heidelberg University
inserted into the host cells,
Hospital, Lusic discovered
which can detect the viral
“The DZIF creates structures
that the viruses frequently
genome in the nucleus and
that make Germany attractive
insert their genetic material
specifically excise it from the
for
elite
researchers.”
into specific regions of the
human DNA. Subsequently,
cell nucleus. Especially often, Prof Dr Gerd Fätkenheuer, Head of the Division of Infectious Diseases,
this should prevent a later
Department I of Internal Medicine of the University Hospital Cologne
the viral genome is found
activation of the “dormant”
directly behind the nuclear
virus. Other projects invespores—the entry channels to the nucleus. “Imagine you are
tigate early HIV infection and their long-term effects,
a visitor to an event and you are late. You will come through
also focussing on patients in Africa in addition to those in
the door and take the first available seat,” Lusic explains.
Germany.
A new approach to treatment and prophylaxis
Antiviral drugs keep HIV under control and delay the onset of AIDS (Acquired Immune Deficiency Syndrome).
However, they have to be taken over a lifetime and frequently have side-effects. They are often too expensive
for patients living in developing countries. Additionally,
the virus easily develops resistance. “We therefore need
new therapies,” explains Prof Gerd Fätkenheuer, Head of
the Division of Infectious Diseases at the University Hospital of Cologne. “Currently, intensive research is ongoing
which investigates how the pathogen can be lured from its
Coordinator:
Prof Dr Hans-Georg Kräusslich
Heidelberg
SCIENCE – TRANSLATION IN FOCUS
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Hepatitis
SCIENCE – TRANSLATION IN FOCUS
Real hope for cure
A hepatitis C virus finds its way into a liver cell using different adhesion and receptor molecules.
The inflammatory liver disease (hepatitis), caused
by infections with hepatitis virus types A to E, is globally widespread. More than half a billion people suffer from chronic hepatitis B, C and/or D infections
worldwide. In the DZIF research field “Hepatitis”,
researchers develop and test new antiviral drugs.
They investigate their mechanisms of action and their
effective combinations. Additionally, they conduct
epidemiological studies to improve patient access to
treatment.
Patients suffering from chronic hepatitis B, C and/or D
infections often have complications and chronic courses
of disease. They have a high risk of developing secondary
diseases such as liver cirrhosis and liver cancer. A vaccine
against the hepatitis B virus (HBV) exists, which simultaneously prevents hepatitis D virus (HDV) infection. Anti-
viral drugs for HBV are also available; they curb viral replication but do not actually cure the disease. There is no
vaccine available against hepatitis C (HCV). Up to now,
the usual treatment of chronic hepatitis C infection has
consisted of a combination of three drugs, one of which
has to be injected regularly.
A cure for hepatitis C
New active agents have changed the treatment of
chronic hepatitis C tremendously. “Hepatitis C is the first
chronic viral infection that has become curable. This is
an enormous success story. It will change medicine,” says
DZIF Professor Michael Manns, Director of the Department of Gastroenterology, Hepatology and Endocrinology at the Hannover Medical School (MHH). “Treatment
now only consists of a combination of several tablets,
can be significantly shortened, causes less side effects
The global hepatitis D registry helps research into new therapies.
and resistance, and is also effective against difficult-toaccess information about their condition to obtain the optreat forms of hepatitis C,” explains Prof Manns. The new
timal treatment. Furthermore, it enables the participating
drugs, for example, inhibit the enzymes RNA polymecentres to get a rapid overview of their patients’ symprase and protease, which the virus needs for both reptoms and therapies. Patients undergo regular follow-up
lication and maturation, thereby suppressing both. The
examinations in which their symptoms, liver and kidney
mechanism of action of the
function, hepatitis serology
“The DZIF pools expertise in molecular
new substance “daclatasand other blood values are
biological processes all the way through to ascertained. Dr Hardtke is
vir” was unknown for a long
time. DZIF Professor Ralf
happy, “In November 2014,
clinical development and launching new
Bartenschlager, virologist at
we registered far over 600
drugs into market.”
the University of Heidelberg,
patients and twelve particiPD Dr Thomas von Hahn, Senior Physician at the Department of
has now deciphered its
pating centres worldwide.
Gastroenterology, Hepatology and Endocrinology at the
mode of action: it binds to
The virus blocker “Myrcludex
Hannover Medical School
the viral protein NS5A. The
B”, developed at the DZIF
virus needs this protein both for replicating its RNA and
partner site Heidelberg, has successfully completed the
assembling new virus particles. However, therapy with
first clinical trial phase and is considered to be an effective
the new active substances is very expensive.
candidate for treating, and possibly even curing, hepatitis
B and D. Furthermore, researchers at the DZIF partner
Hepatitis D: Improving investigations
site Hannover-Braunschweig are looking for biomarkers
and cure rate
that give an indication of the course of disease and effiHDV infection only occurs as a co-infection with hepatitis
cacy of treatment, which subsequently enables individuB, and causes the most aggressive form of viral inflamalised treatment.
mation of the liver. Conventional therapy with interferon alpha has considerable side-effects and only cures
Coordinator:
less than twenty percent of treated patients. Therefore,
Prof Dr Michael Manns
there is an urgent need for new trials to investigate new
Hannover
treatment approaches. The required number of patients
for such trials can only be achieved through international
multicentre trials. A DZIF project at the MHH (HepNet
Study-House of the German Liver Foundation) therefore
established a global registry for patients suffering from
chronic HBV/HDV infection. “The hepatitis D registry is
to enable scientists to investigate the disease,” explains
project coordinator Dr Svenja Hardtke. Patients can better
SCIENCE – TRANSLATION IN FOCUS
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Gastrointestinal Infections
SCIENCE – TRANSLATION IN FOCUS
Targeted treatment instead of
broad spectrum antibiotics
At the DZIF, scientists develop a vaccine to treat Helicobacter pylori.
Gastrointestinal infections are globally widespread and
are not only unpleasant, but also underestimated: according to the WHO, about 1.5 million people die each
year from diarrhoeal disease caused by pathogens like
Salmonella, E. coli and rotaviruses. DZIF scientists in the research field “Gastrointestinal Infections” develop active
substances and vaccines directed at specific pathogens.
Moreover, they investigate measures for diagnosing and
maintaining the natural gut flora which helps to protect
against infections and chronic diseases.
Conventional antibiotic therapy often damages both the
pathogens and the natural gut flora to the same degree.
Using antibiotics can cause a shift in composition of the
gut flora which may facilitate the development of chronic
diseases such as asthma and diabetes. Additionally, antibiotic resistance may develop, consequently leading to infections with difficult-to-treat bacteria. Newer treatment
approaches are therefore not directed at the pathogens
themselves, but against the characteristics of bacteria
that cause illness, so-called virulence factors.
Inhibiting instead of damaging
DZIF researchers at the partner sites Tübingen and
Hannover-Braunschweig, as well as at the University
of Münster, are following the approach of inhibiting
bacteria’s pathogenic characteristics instead of damaging
the actual pathogens themselves. Active agents working
on this principle are called pathoblockers. “They basically
prevent the pathogen from penetrating the gut wall, or inhibit their toxins in the gut,” explains Prof Ingo Autenrieth,
Medical Director of the Institute of Medical Microbiology
and Hygiene at the University Hospital Tübingen. On a
research platform together with DZIF colleagues, Autenrieth and his team are systematically searching compound libraries for such substances. A potential target
with DZIF scientists in Hannover, are developing a therapeutic vaccine: “We want to vaccinate adults infected with
Helicobacter pylori who have not yet developed gastric ulcers or gastric cancer, so as to protect them from developing these conditions,” Gerhard explains. “In 2014, vaccine production was initiated in a spin-off company and
preclinical tests were completed successfully. First clinical
studies are pending.”
Microbiome research
A further focus of the research field is microbiome research.
In January 2014, DZIF scientists at the partner sites HanAn electron microscope portrait of the dreaded gastric pathogen
Helicobacter pylori.
nover, Munich and Tübingen founded the Center for Gastrointestinal Microbiome Research (CEGIMIR) under the
umbrella of the DZIF. This new research platform will more
structure for future antiinfectives could be a type III
intensively investigate the microbial diversity of the gastrosecretion system, commonly found in bacteria which, for
intestinal tract and its role in infections. The alliance aims to
example, salmonella use like
discover diagnostic biomar“The pharmaceutical industry focuses
a needle to inject toxins into
kers that give an indication of
host cells. On their quest for
individual sensitivities to speon high profits—the DZIF on
substances that inhibit this
cific gut pathogens. Based on
high clinical relevance.”
mechanism, the researchers
these, therapies will be detested around 5,000 active
veloped that protect the gut
Prof Dr Ingo Autenrieth, Medical Director of the Institute of
substances, and were suc- Medical Microbiology and Hygiene at the University Hospital Tübingen
flora and/or fortify the imcessful: “We have found a
mune system. “For medicine,
handful of effective substances which could be potential
enormous potential lies in gaining a better understanding
candidates,” Autenrieth says happily.
of the microbiome’s role in health and disease, and the diverse interactions between gut pathogens and gut flora. The
Helicobacter pylori: vaccine instead of antibiotics
DZIF has made it possible for us to pool our research caHelicobacter pylori is also an important gut pathogen. The
pacities in this field and to move forward together quickly,”
bacteria cause gastric infection in half of the world’s popsays Prof Sebastian Suerbaum, Director of the Institute of
ulation. It is the main cause of gastric ulcers and gastric
Medical Microbiology and Hospital Epidemiology at the
cancer. About ten percent of the world’s population deHannover Medical School, and Coordinator of the DZIF revelop a gastric ulcer once in their lifetime; 750,000 peosearch field “Gastrointestinal Infections”.
ple worldwide die of malignant gastric cancer every year.
Antibiotics that are effective against Helicobacter pylori
Coordinator:
exist and therefore also protect against the secondary
Prof Dr Sebastian Suerbaum
complications of infection. However, “Many patients have
Hannover
become untreatable due to antibiotic resistance, and the
rates of resistance are increasing steadily,” adds Prof
Markus Gerhard from the Technische Universität München
(TUM). For this reason, the TUM scientists, in collaboration
SCIENCE – TRANSLATION IN FOCUS
17
18
Infections of the immunocompromised Host
SCIENCE – TRANSLATION IN FOCUS
Decoding the immune system’s
mechanisms
Biological samples are safely cryopreserved in nitrogen tanks.
Pathogens, harmless to healthy people, can become
a life-threatening danger to people with impaired immune systems. These include transplant and cancer
patients, chronically ill people, people with inherited
or acquired immune deficiencies, and elderly patients.
These people are difficult to treat with conventional
antibiotics. The DZIF research field “Infections of the
immunocompromised Host” therefore focuses on investigating immune defects, identifying biomarkers for
infection control, as well as developing new approaches to prevention and immunotherapy.
The prevention and treatment of infections in immunocompromised patients is playing an ever growing role—
especially in the day-to-day life of hospitals. Better
knowledge of the causes and mechanisms of immune
deficiencies form a basis for developing new therapies.
More knowledge about immune deficiencies
“We learn a lot from patients with rare, inherited
diseases of the immune system,” emphasizes DZIF Prof
Christoph Klein, Director of LMU Munich’s Dr. von
Hauner Children‘s Hospital. In order to understand these
immune defects, Klein and his team look for the gene
loci and gene products of impaired functions. In doing
so, they have found a defective gene which codes for
“Jagunal 1” (JAGN1), an important transport protein. It
regulates the function of neutrophil granulocytes, cells
of the immune system important for the defence against
fungal infections. The researchers investigated JAGN1
gene defects in mice, and discovered that administering them with a certain granulocyte stimulating factor
had a protective effect against infections with Candida
albicans, a type of yeast which is responsible for many
fungal infections in humans. Clinical trials now need to
be conducted to investigate whether this is a treatment
19
can be used: their infection is controlled by T
lymphocytes, in short T cells, that specifically target EBV.
In the same manner, immunocompromised lymphoma patients can be cured with infusions of EBV-specific
T cells. In order to develop these treatment approaches
More immunotherapy for cancer patients
further, Behrends and her team investigated the effect of
DZIF scientist Prof Uta Behrends, from the university
different EBV-specific T cells in mouse models. The result
hospital of the Technische Universität München, found
was surprising: “Lymphoma growth was inhibited by some
a piece of the puzzle which helps understand the conT cells, promoted by some and unaffected by others,”
nections between infections,
says Behrends. Treatment
“Physicians and scientists from the most
the immune system and canwith solely tumour inhibiting
cer. It involves the EpsteinEBV-specific T cells could
varied disciplines come together at the
Barr virus (EBV). Most people
therefore further improve
interfaces of DZIF projects – in this lies the
in Europe contract this virus,
efficacy of current immunogreatest potential for innovation.”
but the infection goes untherapy approaches.
noticed in most cases. The
Prof Dr Christoph Klein, Director of the Dr. von Hauner
pathogen remains “hidden”
Another important project
Children‘s Hospital, Ludwig-Maximilians-Universität (LMU) München
in infected cells over many
in the research field is to
years. It often only becomes noticeable when the incontinuously develop the Transplant Cohort. Here,
fected person develops a weak immune system, as
transplant patients are examined before and after procehappens with blood stem cell and organ transplants.
dures, medical data and samples are collected and anaThese patients then suffer more frequently from cancer
lysed. In doing so, researchers want to find out why some
of the white blood cells, so–called lymphomas. EBV
patients are more susceptible to infection than others.
is an important stimulus for developing lymphoma in
patients who have had a transplant. To treat these
Coordinator:
patients, the same defence mechanism that protects
Prof Dr Dirk Busch
EBV-infected people with healthy immune systems
München
The Epstein-Barr virus can “hide” in infected cells over many years.
SCIENCE – TRANSLATION IN FOCUS
option transferable to humans. “Each defect we identify
is like part of a puzzle. The more of these we find, the better we can understand the immune system’s mechanisms
and can also treat other patients,” Klein stresses.
20
Healthcare-associated and Antibiotic-resistant bacterial Infections
SCIENCE – TRANSLATION IN FOCUS
Getting hospital pathogens
under control
The emergence of resistance is monitored in hospitals, as is antibiotic use.
Hospital pathogens are one of the biggest challenges in
healthcare. According to the German Society for Hospital
Hygiene, approximately 900,000 hospital-acquired
infections occur in Germany every year. The threat of
falling back into a “pre-antibiotic era” is growing, especially because of the increase in antibiotic-resistant pathogens. In order to better control the pathogens, DZIF
scientists in the research field “Healthcare-associated
and Antibiotic-resistant bacterial Infections” are concentrating on several issues simultaneously: they are
encouraging a more targeted use of antibiotics, looking
for new active substances, and developing improved
hospital hygiene management.
In particular, intensive care units run a high risk of developing and spreading multidrug-resistant pathogens.
Especially the inappropriate use of broad spectrum antibiotics is promoting an increase in resistance. This results in
longer and more severe courses of disease, along with
higher treatment costs. Methicillin-resistant Staphylococcus
aureus (MRSA) strains and multidrug-resistant gramnegative Enterobacteriaceae are especially dreaded in
hospitals. Some pathogens have even become insensitive to the “last resort” antibiotics that are reserved for
emergencies only.
Mobile resistances identified and stopped
At the University Hospital of Gießen, Dr Can Imirzalioglu
and his team also encountered this problem. During a
routine examination in a hospital in Hessen, they identified various bacteria that produced carbapenemase.
This enzyme renders carbapenem, a “last resort” antibiotic, ineffective. “As very different bacteria produce
this enzyme, we suspected that its genetic information
may not be located on a bacterial chromosome, but on
a plasmid,” says Imirzalioglu. These plasmids, or mobile
experts recommend using “antibiotic stewardship” programs, ABS for short. Here, a multidisciplinary team
advises hospital colleagues on selection, dose and administration of an optimal antibiotic. It recommends specific antibiotics for certain diseases and excludes others.
ABS experts also compile lists of recommended drugs
for hospitals, and monitor antibiotic usage, as well as the
emergence of resistance. First results, including those
from DZIF studies, show: 10-40 percent of the administered drugs can be omitted, the duration of treatment
can be shortened, and resistance can be reduced in the
long-term.
Keeping an eye on the pathogens: controlling growth
In collaboration with an international team, Prof Evelina
in a petri dish.
Tacconelli, Head of the Division of Infectious Diseases
at the University Hospital Tübingen also developed
genetic elements, consist of short ring-shaped DNA
European guidelines for controlling multidrug-resistant
and can easily transfer resistance between bacteria.
gram-negative bacteria. In view of the increasing spread
And indeed, in each sample, the DZIF bioinformaticiof pathogens across all borders, the DZIF researcher
ans in Gießen localised a
underlines the importance
“The
DZIF
is
a
pioneer
in
translational
resistance-gene encoded in
of Europe-wide recomresearch in Europe, particularly
a plasmid. For the first time
mendations. “This is partiin the world, they successcularly important for counin the field of multidrug-resistant
fully identified and charactries which do not have
hospital pathogens.”
terised the mobile genetic
national guidelines of their
Prof Dr Evelina Tacconelli, Head of the Division of Infectious Diseases,
element as responsible for
own,” Tacconelli thinks. She
Department for Internal Medicine I at the University of Tübingen
transferring the carbapebrings expertise in infection
nem resistance while the outbreak was still ongoing. In
research, which she gained in other European countries,
doing so, they could rapidly identify the source of infecto the DZIF. Further projects in this research field focus
tion and the routes of spread, and therefore contain the
on developing new substances that inhibit colonisation
outbreak.
of multidrug-resistant Staphylococcus, as well as measures against multidrug-resistant Enterobacteriaceae in
Antibiotic stewardship: reducing resistance in the
cancer patients.
long-term
Together with other scientists, Prof Winfried Kern, Head
Coordinator:
of the Division of Infectious Diseases at the University
Prof Dr Andreas Peschel
Medical Center Freiburg, developed guidelines for antiTübingen
biotic use in hospitals, as a prevention measure against
hospital pathogens. “Treatment has become so complicated that a surgeon will almost be unable to select
a correct antibiotic without consulting an infectious diseases specialist,” is how the DZIF researcher describes
the situation. In the national guidelines, issued in 2014,
SCIENCE – TRANSLATION IN FOCUS
21
22
Novel Antiinfectives
SCIENCE – TRANSLATION IN FOCUS
Finding valuable natural
treasures
They co-discovered a novel antibiotic: Anna Müller, Ina Engels, Prof Tanja Schneider and Dr Till Schäberle.
Medicine without antibiotics is no longer imaginable.
They are the most important agents against infectious
diseases. However, more and more pathogens are
developing resistance, making the former “silver
bullets” less and less effective. Although there is a
great need for antibiotics, the pharmaceutical industry
has hardly introduced any new ones to market – they
are not lucrative enough. The research field “Novel
Antiinfectives” is counteracting this development:
it identifies new target structures for antibiotics,
develops candidate agents and strategies for fortifying
the body’s immune defence.
Fungi and bacteria produce active substances to protect
themselves against other microorganisms, amongst
which new antibiotics could potentially be found.
Scientists comb through natural substances in marine
sediments, soil and animal excrements in pursuit of such
organisms. DZIF researchers see a particularly high
potential in soil bacteria. However, less than one percent
of all bacteria and fungi are cultivatable in conventional
culture media. The quest for antibiotics is painstaking
and has a low rate of success.
Valuable resource against gram-positive bacteria
Together with DZIF members, an international team of
researchers from the USA, took the trouble of searching
and was rewarded: thanks to a special culturing method,
the scientists were able to isolate previously uncultured ground bacteria, and subsequently discovered an
untapped source of new antibiotics. By means of a new
screening method, they discovered “teixobactin”. Prof
Tanja Schneider, leader of a DZIF junior research group
at the University of Bonn, is happy, “It is a highly interesting active substance and the first member of a new class
of antibiotics.” The biologist and her team deciphered its
The newly discovered cystobactamides could be effective against
gram-negative bacteria (here: EHEC pathogens).
Bacteria of the species Pseudomonas aeruginosa (in the photo) can
cause infections if the immune system is weakened.
“We have discovered a completely new substance class,
and have christened it ‘cystobactamides’.” In tests, they
have been effective against the gram-negative bacteria
Escherichia coli and Acinetobacter baumannii. The active
substance works by preventing bacterial DNA from
being compacted like a twisted garden hose. Interfering
with this process, results in the bacteria’s metabolism
becoming impaired. By chemically modifying the active
substance, the researchers hope to enhance this effect
and broaden the spectrum of targetable bacteria. “If we
succeed in doing this,” says Müller, “cystobactamides will
be a real beacon of hope in the fight against hospital
pathogens.”
Furthermore, the DZIF scientists analyse microbial genomes at the partner site Tübingen. With new techniques, such as genome mining, they looked for “silent”
mechanism of action: “Teixobactin simultaneously targene segments which could code for potential active
gets many different important sites in bacterial cell wall
substance syntheses. After activating these gene clussynthesis, and makes it almost impossible for bacteria
ters, the scientists discovered promising active substanto use their adaptation strategies,” Schneider emphaces in the glycopeptide class. In 2014 alone, the DZIF
sises. In first tests in mice,
research field “Novel Antithe substance was effective “Thanks to the DZIF interactions, we focus
infectives” discovered a toagainst numerous probletal of three new classes of
our basic research a lot more on what is
matic gram-positive bacteria
antibiotics. The chemists now
important for hospitals.”
and did not cause resistance.
need to work at optimising
Prof Dr Rolf Müller, Managing Director of the Helmholtz Institute
The scientists consider it to
the candidate active subsfor Pharmaceutical Research Saarland (HIPS)
be a promising new drug
tances, for good tolerability,
candidate against bacteria such as Staphylococcus aureus
effectiveness against a broad spectrum of pathogens
and Mycobacterium tuberculosis.
and to prevent the development of resistance as far as
possible.
Beacon of hope in the fight against
hospital pathogens
Coordinator:
Gram-negative bacteria are even more challenging: “They
Prof Dr Hans-Georg Sahl
have two cell membranes. Potential agents have to
Bonn
penetrate through both to be effective,” explains
Prof Rolf Müller, Director of the Helmholtz Institute for
Pharmaceutical Research Saarland (HIPS). Despite
complex requirements, Müller and his colleagues from
Saarbrücken succeeded in isolating an active substance
from myxobacteria at the Helmholtz Centre for Infection Research (HZI) in Braunschweig. Müller is happy,
SCIENCE – TRANSLATION IN FOCUS
23
24
Product Development Unit
RESEARCH INFRASTRUCTURES
Well-supported, from the
target molecule to approval
to identify promising approaches for potential products
and assess the prospects of their further development.
Conrad emphasizes the benefit of contacting the office
early on: “Researchers are welcome to get in touch from
the moment they have a good idea for a potential product.” This is how the utilisation of scientific insights and
the subsequent realisation of medicinal products can be
improved. Once the pilots are on board, they provide advice and support for developing trial designs, planning and
managing product development, for questions about clinical testing as well as for marketing approval.
With the help of the “Product Development Unit” at the DZIF,
a phase I trial for an Ebola vaccine candidate was initiated.
The journey from discovering a new target molecule in
the body to the approval of a suitable drug takes years.
95 percent of all active agent candidates fail before
the clinical trial stage. Developing a new drug requires
knowledge of the regulatory requirements, production
and patents. Here, the DZIF’s “Product Development
Unit” advises and supports its colleagues.
The DZIF infrastructure consists of two offices. The
Translational Project Management Office (TPMO) at the
Helmholtz Centre for Infection Research in Braunschweig
develops plans for drug development, assists with their
implementation, and advises on commercial matters. The
Office for Scientific and Regulatory Advice (OSRA) at the
Paul-Ehrlich-Institut in Langen advises on the approval of
clinical trials, therapeutic agents and vaccines. OSRA also
analyses typical obstacles in drug development and ways
of avoiding them.
From idea to product
“We are like pilots guiding the way through the thicket
of regulations and product development,” is how Dr
Christoph Conrad from the Paul-Ehrlich-Institut describes
OSRA and TPMO’s responsibilities. He, along with his
colleagues, join the DZIF research fields’ work meetings
From the Ebola emergency to a successful vaccine
The DZIF activities during the Ebola outbreak in 2014
exemplify how the infrastructure successfully manages
complex and critical translational projects. With the help
of the “Product Development Unit”, important stakeholders were brought together to promptly initiate a clinical
phase I trial for the candidate vaccine “rVSV-ZEBOV” in
Germany. The DZIF infrastructure played a decisive role
in this as a point of contact with the WHO, the Canadian health authority Health Canada, which developed the
vaccine, the licensee NewLink, sponsors, the trial centre
and the applicants as well as the authorities concerned.
This enabled the development of a promising candidate
vaccine within a few months, which was subsequently
available for further trials.
Coordinator:
Prof Dr Klaus Cichutek
Langen
Clinical Trial Unit
25
Human trials for humans
Consistently high quality standards are implemented across the
DZIF’s clinical trial units.
New drugs have to be tested thoroughly in clinical trials
before they can be brought onto the market. The DZIF
“Clinical Trial Unit” (CTU) consists of clinical trial units
specialised in infectious diseases. Here, active substances are medically tested under the highest quality
standards.
Good internal collaboration paves the way
to external collaboration
The networking infrastructure between the partner sites,
consistently high quality standards, efficient operating
procedures, and experience in collaborating between
academic partners and companies make the units suitable
for clinically testing active substances, and this is true not
only for substances developed within the DZIF. “A network that maintains quality standards like these is highly
valuable to the industry,” explains Angela Steinbach, the
CTU project manager. One major advantage of the CTU
is that one central contact person enables access to many
trial units. Furthermore, this expertise strengthens the
DZIF’s position as a partner in international infectious disease networks.
Coordinator:
These clinical trials test tolerability, efficacy and dosages
of drugs and vaccines. In Germany, strict regulations and
standardised operating procedures must be adhered to.
Research on humans demands competency, precision and
utmost attention. In order to ensure reliable results, clinical trials have to be planned thoroughly in advance, conducted in a controlled environment, tested systematically
and evaluated carefully.
DZIF quality objectives are external signs of quality
Currently, eleven clinical trial units are working together
within the DZIF infrastructure. The “Coordinating Office”
in Cologne has longstanding experience with which it coordinates the alliance, manages feasibility requests and
the central management system. In 2014, its main focus
was to implement a comprehensive strategy for conducting clinical trials in all participating DZIF clinical trial units.
“We have established a joint quality management system,”
Prof Dr Oliver Cornely
Köln
RESEARCH INFRASTRUCTURES
explains Prof Oliver Cornely, Coordinator of the DZIF infrastructure. This system is based on so-called Standard
Operating Procedures (SOPs), as has been recommended by the Federal Ministry of Education and Research
(BMBF).
26
African Partner Institutions
RESEARCH INFRASTRUCTURES
Reliable alliances in
areas of risk
Tracking pathogens locally
Together with their African colleagues, DZIF researchers
conduct epidemiological surveys to better understand
the temporal and spatial distribution of pathogens in the
affected areas. In one trial, conducted at all four partner
institutions, the teams collected samples from children
with severe febrile illnesses. The samples were initially
analysed on-site with rapid tests and microbiological investigations, and later in Germany with special molecular
diagnostic tests. Besides malaria parasites, other pathogens were often found to be the cause of life-threatening
febrile illness in children.
Trial participants were also recruited from the Agogo Presbyterian
Hospital in Ghana.
Like many other infectious diseases, AIDS, tuberculosis
and malaria occur rarely in Germany. They are, however, widespread in many parts of Africa. In order to
better investigate these diseases, the DZIF institutes
foster partnerships with research establishments on
the African continent.
The DZIF promotes collaborations between its partner
sites and renowned research establishments in Ghana,
Gabon, Burkina Faso and Tanzania. “The DZIF institutions
have been working together with these partners for over
a decade,” says Prof Jürgen May, Coordinator of the infrastructure “African Partner Institutions”. Thanks to longstanding relationships, contacts and agreements in these
reliable alliances have existed for years. They offer DZIF
researchers excellent administrative and logistic conditions on the ground: from the provision of accommodation and modern laboratories to infrastructures for
clinical trials all the way through to facilitated import and
export arrangements for research projects. The Ebola
virus vaccine efficacy trial conducted in Gabon, once again
demonstrated the potential in these partnerships.
Improving on-site diagnostics
“We therefore want to improve bedside testing,” says
May, “and aim to find simple methods, particularly for regions with limited access to health care.” Together with
the Fraunhofer Institute for Silicon Technology, DZIF researchers are developing a new diagnostic testing kit
which rapidly analyses blood samples using microchips.
The chips will analyse a choice of eight biomarkers in a
convenient device with a modular design. The biomarkers
can be selected according to the needs in the respective
areas.
Coordinator:
Prof Dr Jürgen May
Hamburg
Natural Compound Library
27
From gene sequences of bacterial strains, Nübel can read
the course of infectious disease outbreaks or the spread
of resistance, and can identify the potential in new active
substances. Prof Mark Brönstrup, who heads the Department of “Chemical Biology” at the HZI, paves the way to
new drugs. Under a DZIF professorship, he is looking for
new testing systems and contributing to developing and
optimising active substances. In doing so, he draws on his
experience from the pharmaceutical industry.
The DZIF’s “Natural Compound Library” provides researchers with
sufficient substances to “fuel” investigations.
Microorganisms not only cause infections, they also
produce substances that can fight other pathogens.
Most antibiotics have been developed from such natural
substances. However, up to now, only a few substances
have been investigated for their medicinal effects. In
the “Natural Compound Library”, the DZIF has collected
compounds from bacteria, fungi and plants. They are
available for research to all DZIF establishments.
Ordering substances from the library
In the long term, an extensive chemical substance library is
to be established and made available to the DZIF research
fields for screenings. “We have resources for both functional genomics and fermentation, as well as for developing
active substance screenings,” emphasises Prof Rolf Müller,
Coordinator of the infrastructure “Natural Compound
Library”. “In this way, at the request of DZIF colleagues, we
can identify substances, reproduce them in a milligram to
gram range and send them in minimal amounts on microarray plates along with thousands of other substances.”
This testing system permits researchers in the different
research fields to conduct rapid, parallel analysis in their
quest for active substances.
Coordinator:
DZIF researchers can draw on collections from the
Helmholtz Centre for Infection Research (HZI), the
Helmholtz Institute for Pharmaceutical Research
Saarland (HIPS), the Hans Knöll Institute in Jena as well as
the University of Tübingen. These establishments isolate
and characterise microorganisms and fungi that produce
potential active substances, and subsequently analyse
them with methods from system biology, biotechnology
and functional genomics.
New experts from research and industry
Prof Ulrich Nübel brings his expertise in gene function
research to the DZIF. He has been Professor of “Microbial
Genome Research” at the German Collection of Microorganisms and Cell Cultures (DSMZ) since June 2014.
Prof Dr Rolf Müller
Braunschweig/Saarbrücken
RESEARCH INFRASTRUCTURES
Collected works
of nature
28
Biobanking
RESEARCH INFRASTRUCTURES
Reserved for future
eventualities
provide safe, high-quality, precisely characterised and
standardised biomaterials. “Besides this, we advise researchers on selection, transport and condition of the
samples, and provide support for project design,” says
Schirmacher. Supported by a laboratory information management system (LIMS), the biobanking platform is establishing a data and sample collection from transplant patients, for the National Transplant Cohort, an initiative of
the research field “Infections of the immunocompromised
Host”. This future project will broadly investigate the influence of infections on immunocompromised patients.
From 2015, approximately 800 patients per year will be
enrolled in the trial and registered in the biobank.
DZIF biobank samples are stored in large nitrogen tanks.
Biological samples constitute important materials for
infection research. The infrastructure “Biobanking”
provides DZIF researchers with samples of body fluids,
tissues and microorganisms. On this account, the DZIF
has established a biobanking platform with respective
technologies.
“The infrastructure ‘Biobanking’ has already supported
over 70 projects in different research fields,” summarises Coordinator Prof Peter Schirmacher. Here, all
samples important to infection research are collected and
documented: the Helmholtz Zentrum München archives
fluid samples such as serum, plasma and urine while the
German Collection of Microorganisms and Cell Cultures
in Braunschweig stores pathogens and other microorganisms. The DZIF tissue bank at the Heidelberg
University Hospital collects infected tissue samples and
coordinates the entire biobanking infrastructure.
Long-term use for everyone
Equipped with a bar code, the samples are computerdocumented and stored at temperatures down to -196° C.
The samples are rapidly found electronically and, in part,
even withdrawn under robot control. Thanks to these
latest technologies, the DZIF biobanking platform can
Accessible to everyone
In order to make materials available to as many researchers as possible, the existing collections important
for research will be integrated into the DZIF Platform.
Additionally, other biobank stocks will be registered and
linked throughout Europe. Furthermore, the DZIF biobanking platform coordinates and organises the meetings for the IT and biobanking working group within the
German Health Research Centres (DZG).
Coordinator:
Prof Dr Peter Schirmacher
Heidelberg
Bioinformatics
29
colleagues at “www.bioinformatics-platform.dzif.de”. It
includes a databank with thousands of sequenced common pathogen genomes and current outbreak strains. Besides this, registered users can have access to specifically
tailored software, with which they can, for example, rapidly
compare typical virulence genes to strains in the databank
and identify epidemiological connections. In future, this will
enable calculations of risk potentials – using methods similar to those used for weather forecasts.
A huge databank with sequenced pathogen genomes is made
available to all DZIF researchers.
Biotechnological advances have revolutionised the diagnosis of infectious diseases: nowadays, genetic decoding
of microorganisms is possible in a matter of days, at decreasing costs and with increasing quality. However, the
challenge of processing the obtained data remains. The
DZIF infrastructure “Bioinformatics” helps researchers
make use of these data.
Making bioinformatics easier to understand
The infrastructure holds workshops to enable as many
scientists as possible to handle the service’s software independently. In these popular, hands-on workshops, DZIF
researchers learn how to manage the different functions,
and how to programme on their own. “We want to make
bioinformatics less daunting and make it a simple, userfriendly technology for everyone,” Chakraborty hopes.
The workshops have been in high demand, also attracting
external researchers. This is why the range of courses offered is being expanded and also being made available to
scholarship holders at the DZIF Academy.
Coordinators:
Participants in this infrastructure include Gießen University and the Helmholtz Centre for Infection Research
(HZI) in Braunschweig. Together, they have established
three service areas: “Information transfer”, which advises
and informs DZIF colleagues on specific questions; the
“Bioinformatics Resource Center” (BRC), which provides
analysis software tailored to the specific problems of the
researchers; and “Training activities”, where bioinformaticians offer workshops to familiarise researchers with
tools for managing the technologies.
Making information and software accessible
“We have a data explosion,” says Prof Trinad Chakraborty,
Coordinator of the infrastructure, “and we need systems
that not only store data, but also make it interpretable for
everyone.” For this reason, the bioinformaticians established a platform in 2014, which offers its services to DZIF
Prof Dr Alice McHardy
Braunschweig
Prof Dr Trinad Chakraborty
Gießen
RESEARCH INFRASTRUCTURES
Harnessing information
on infections
30
DZIF Academy
PROMOTION OF YOUNG RESEARCHERS
Investing in future infection
researchers
time, and also the DZIF Prize for Translational Infection
Research. Prof Ulrike Protzer, Coordinator of the DZIF
Academy is happy, “We had excellent stipend holders in
2014, as the awarded national and European research
prizes show – an example being the highly competitive
‘Young Investigator Award from the European Association for the Study of the Liver’.” With this, she especially
highlights the scientific accomplishments of women at the
DZIF. “Maternity leave stipends are very supportive as
they give young mothers the freedom to combine having
children with having a career.”
The DZIF Academy makes young physicians and scientists
enthusiastic about infection research.
The best investment into infectious disease research is
to further the talents of the next generation. Promoting
junior researchers is therefore of major importance to
the DZIF. The DZIF Academy offers physicians and scientists career opportunities in the fields of clinical infectology, microbiology, virology, immunology and molecular medicine.
The virtually organised Academy promotes talents across
the DZIF partner sites. To this effect, it offers stipends to
medical students, for structured doctoral programmes.
It also has a clinical leave programme, to support young
hospital doctors who are interested in infectious disease
research. Additionally, an exchange programme enables
participants to gain insights into other DZIF establishments, and maternity leave stipends assist female scientists to return to their professions after having children.
Stipend holders can deepen their knowledge at the spring
and autumn school seminars – in both basic research and
clinical topics.
Excellent support for excellent researchers
In 2014 alone, the Academy supported 52 junior talents.
Furthermore, together with the scientific societies, it
awarded prizes to successful doctorates for the first
Clinic, Child and Career
Dr Sandra Ciesek is also delighted with the support. The
DZIF is funding half of her salary during her two-year-long
maternity leave stipend. “This enabled me to start again
earlier,” the doctor says. Ciesek started working at the
Hannover Medical School when her daughter was four
months old: she now works mornings in the outpatient
clinic. In the afternoons, she has time for her hepatitis C
virus research, writes applications for new projects, and
instructs scientific staff. At around 4.00 pm, she picks up
her daughter from the crèche, and when the little one is
asleep in the evenings, Ciesek writes her publications.
“This work model is ideal, because I can divide my time,”
she says with a smile. “Another advantage is that it enables
me to stay connected with research.” And this paid off well
for Sandra Ciesek: as a young mother she was offered a
professorship.
Coordinator:
Prof Dr Ulrike Protzer
München
Collaborations at the DZIF
31
to call on thousands of people, often in very remote areas.
In one of the EBOKON projects, DZIF researchers at the
Helmholtz Centre for Infection Research (HZI), together
with partners in Nigeria, the Hasso Plattner Institute and
the software producer SAP, are currently jointly developing an innovative IT system to monitor contact persons:
thanks to a new app, Nigerian health authority staff could
interview affected people via mobile phone, and record
and follow up the results in a central registry. “We tailored
our system to the needs of the local authorities and the
WHO,” says project leader Prof Gérard Krause from the
HZI.
Inconspicuous, but dangerous: Ebola viruses caused the 2014
Ebola epidemic in West Africa.
Scientists from research establishments, university hospitals and federal research institutes collaborate at the
DZIF. During the most recent Ebola epidemic in West
Africa, DZIF colleagues experienced how important this
collaboration is and how much more can be achieved
when you are “united against infections”.
“DZIF members were on the ground from the start of
the Ebola epidemic in April 2014,” emphasizes Prof Martin
Krönke, Chairman of the DZIF Executive Board. The
epidemic spread so rapidly, that the WHO declared it
an international public health emergency in August. The
DZIF thereupon initiated a research consortium called
‘EBOKON’, now being funded by the German Federal
Ministry of Education and Research with 2.3 million Euros.
Ten research projects are being conducted – with topics
spanning from developing new vaccines against Ebola to
analysing the process of infection all the way through to
epidemiological questions.
Mobile telephones for monitoring contact persons
Up to then, Ebola outbreaks could be well-contained by
isolating ill people and the people they had come into
contact with. However, in the most recent epidemic,
monitoring and looking after these people meant having
International collaboration for vaccine trials
Another project clinically tested the vaccine candidate
“VSV- ZEBOV”. “We were in contact with the WHO, which
provided the vaccine and coordinated the preparations,
almost on a daily basis,” says Marylyn Addo, DZIF professor
at the University Medical Center Hamburg-Eppendorf
(UKE). She led the first clinical trials on healthy adults there.
The same vaccine trial was simultaneously conducted in
Gabon. DZIF colleagues from the Paul-Ehrlich-Institut
provided advice to the researchers for the approval process. EBOKON Coordinator Prof Stephan Becker and his
team from the high-security laboratory at the PhilippsUniversität Marburg investigated whether test persons’
immune responses to the vaccine were sufficiently high
to be effective against live Ebola viruses. The results are
good: “The vaccine can potentially be used to protect
against Ebola,” says Becker.
COLLABORATIONS AT THE DZIF
United against Ebola
32
DZIF Highlights 2014
DZIF Highlights 2014
DZIF HIGHLIGHTS 2014
January
DZIF researchers in Hannover,
Munich and Tübingen sign a
cooperation agreement for the new
Center for Gastrointestinal Microbiome
Research (CEGIMIR). This new research
platform enables more intensive
investigations on the gastrointestinal
tract’s microbial diversity and its
role in infections.
On
28 January,
the DZIF’s Transplant Cohort is founded at its first General
Assembly in Frankfurt
am Main.
May
A model project
at the University Medical Center Freiburg proves
that targeted reduction of the
use of antibiotics in hospitals
is possible. The intelligent use
of antibiotics is an important
strategy in the fight against
multi-drug resistant
bacteria.
The Universität zu Lübeck and
the Research Center Borstel jointly
establish a new Professorship for
Molecular and Experimental Mycobacteriology at the German Center
for Infection Research (DZIF), to
which Dr Stefan Niemann is
appointed.
April
A phase I clinical trial is
initiated at the Institute for
Tropical Medicine of the
University Hospital Tübingen,
to test the efficacy and safety of
a promising vaccination
method against
malaria.
February
An international research team led by
Prof Mathias Heikenwälder and
Prof Ulrike Protzer, Institute of Virology
at the Helmholtz Zentrum München and the
Technische Universität München discover
a way of specifically targeting and eliminating
hepatitis B viruses’ genetic information
“hidden” in the cell nuclei of liver cells.
The scientists publish their results
in the journal Science.
March
Marina Lusic takes up a
professorship in Heidelberg in the research
field “HIV”.
33
The microbiologist and
population geneticist Prof Ulrich
Nübel was appointed to a DZIF
professorship, at the Leibniz
Institute DSMZ (German
Collection of Microorganisms
and Cell Cultures) in
Braunschweig.
On 1 July 2014, Prof Christoph
Lange takes up the professorship
“International Health/Infectious
Diseases”, which was established
in a collaboration between the
Research Center Borstel,
the Universität zu Lübeck
and the DZIF.
Start of preclinical trials for a potential
vaccine against the “Middle
East Respiratory Syndrome
coronavirus”, MERS-CoV for
short, led by DZIF researcher
Prof Gerd Sutter from the
Ludwig-MaximiliansUniversität
München.
September
October
The DZIF initiates a consortium
to strengthen Ebola research:
“EBOKON” will be supported
by the Federal Ministry
of Education and Research with
2.3 million Euros until the
end of 2015.
At the ICAAC in Washington,
the world’s largest conference on
antimicrobial agents and infectious
diseases, the DZIF contributes
with scientific presentations and
is represented by its own
exhibition stand.
November
A clinical phase 1 trial for a
potential vaccine against the dreaded Ebola virus is ready to begin.
The trial is supported by the DZIF
and led by two DZIF professors at
two locations – in Hamburg und
Lambaréné, Gabon.
December
The virologist Prof Stephan
Urban from the Heidelberg University is awarded the DZIF Prize for
Translational Infection Research
worth 5,000 Euros. It is awarded
at the DZIF Annual Meeting
for the first time.
DZIF HIGHLIGHTS 2014
July
June
34
Science and public
SCIENCE AND PUBLIC
Increasing DZIF visibility,
nationally and internationally
The brochure “Translation City” explains the DZIF’s research activities.
Looking back on the year 2014, the first thing we, in
the communication department, think about is Ebola.
The epidemic, which became apparent in spring 2014,
took up a large segment of our media work, and rightly
so. Over and over again, experts from the DZIF made
themselves available to journalists for questions and interviews. They also provided further information about
Ebola research work, including the development of an
Ebola vaccine, which was of great public interest.
Classic media work is essential
In 2014, the DZIF published two to three press releases
per month. Besides Ebola, the MERS coronavirus was
also a central issue, which the research field “Emerging
Infections” is also investigating intensively. Furthermore, there were research reports on tuberculosis,
novel antibiotics and antibiotic resistance, as well as
hepatitis and other infectious diseases – all interesting
topics that were taken up by the media.
What does the DZIF accomplish? What fields of research
does it cover, and what is special about this network that
has united 32 (recently increased to 35) member establishments “under one roof” since it was founded? Providing answers to these questions and making the activities
externally visible – those are the most important responsibilities of the Press and Public Relations Office.
Information accessible at the click of a mouse
Besides media work, continuously updating and developing the DZIF website plays a key role in the DZIF’s public
presentation. Here, different target groups can obtain relevant information with only a few mouse clicks. Around
42,000 visitors took advantage of the DZIF website’s services in 2014.
In addition to presenting itself virtually, the DZIF is attending more and more events and fairs to connect with
35
The German Centres discuss their work with politicians at a dinner
debate in Berlin (centre of photo: Prof Winfried Kern).
Communicating during breaks was also part of the DZIF Annual
Meeting’s programme.
Strengthening the network with
internal communication
An association like the DZIF, which unites around 250
scientists and physicians at different partner sites
throughout Germany, can only function with good internal communication. The Press and Public Relations
Office supports internal communication with a quarterly newsletter and via the DZIF intranet, an exchange
platform equally accessible to everyone. Collecting and
channelling information from all parties, and serving as
an interface between research and the public is also important for a properly functioning network.
Face-to-face contact remains essential, despite the era
of Facebook, telephone conferencing and e-mailing.
The Annual Meeting 2014 demonstrated this, where
around 250 DZIF members came together for three
days to present the progresses and objectives of their
research activities, as well as for discussions. This lively
conference which took place in Braunschweig, the Main
Office’s location, impressively highlighted the DZIF’s
accomplishments to date.
Press and Public Relations:
Janna Schmidt
Karola Neubert
potential partners. Exhibition stands at the Permedicon
and the Congress for Infectious Diseases and Tropical
Medicine in Cologne, as well as the “Interscience Conference on Antimicrobial Agents and Chemotherapy”
in Washington, contribute to making the DZIF known,
nationally and internationally.
Classic print media continue to play an important role in
the DZIF’s public presentation: with a focus on special
ideas and quality. To this end, an image brochure was conceptualised at the end of 2014 and published in 2015. It
brings DZIF scientists working all over Germany closer
together in the so-called “Translation City”. The virtual
SCIENCE AND PUBLIC
research centre was transformed into a city that accommodates for joint research activities on infectious diseases. Short routes, intensive networking and an infrastructure for everyone – this is what the DZIF offers.
36
Collaborations with scientific institutions and industry
COLLABORATIONS
External Collaborations
Networking with external partners has been on the DZIF‘s agenda from the start.
Numerous associated partnerships and other external collaborations reinforce the DZIF’s position as a
top-class institution in the field of infection research.
and the studies were initiated. Additionally, the Charité
held training events for practice-based physicians. Furthermore, the Charité organised a multicentre study on
infection prevalence at admission, running under ATHOS.
DZIF’s associated partners
Friedrich-Loeffler-Institut, Riems
(DZIF member since June 2015)
The Friedrich-Loeffler-Institut (FLI) is partner in a collaborative project aimed at the early detection of pathogens, particularly those transmitted from animals. The FLI
provides the necessary blood and tissue samples, as well
as nucleic acid preparations, from both domestic and wild
animals. Especially the unique laboratory and animal testing facilities, with biosafety levels 2 to 4, make the FLI an
important partner for the DZIF.
Charité – Universitätsmedizin Berlin
Charité – Universitätsmedizin Berlin is partner in a study on the intelligent use of antibiotics (ATHOS: antibiotic
therapy optimisation study). It investigates whether interventions for targeted antibiotic use in hospitals (antibiotic
stewardship see University Medical Center Freiburg) and
in practices (Charité) influence the number of new cases
of infection with certain antibiotic-resistant bacteria. A
method which was developed in the new module “ATHOSMRE-Surveillance” at the Charité is being used to monitor
the multidrug-resistant organisms. In 2014, hospital staff
from six university hospitals were trained to use this tool
German Liver Foundation/HepNet Study-House,
Hannover
The HepNet Study-House networks trial centres for
hepatitis research, and provides a platform for conducting
clinical trials. The DZIF can use the infrastructures and
cohorts for its projects. Current research activities are
focussing on hepatitis B, C, D and E. In 2014, a project on
hepatic encephalopathy was initiated together with the
German Liver Foundation. We report on the establishment of a hepatitis D registry on page 15.
Goethe University Frankfurt am Main
A project focussing on hepatitis, in which clinical cohorts
are being established, is currently ongoing at the Goethe
University Frankfurt am Main. Blood samples taken
from patients before therapy or after therapy failure are
available to all collaborating partners. The clinical data,
along with viral and host gene analysis and phenotypic
results, are being analysed and recorded in an onlinebased tool. This tool aims at improving the evaluations
of courses of disease and treatment responses, and to
tailor individual treatment.
Gottfried Wilhelm Leibniz Universität Hannover
DZIF scientists recently discovered a completely new
substance class called cystobactamides, which is effective against difficult-to-treat gram-negative bacteria. A
project at the HZI aims to develop these cystobactamides further, so that they can undergo testing as potential
antibiotics in preclinical trials. Scientists at the Leibniz
Universität Hannover succeeded in conducting the
first total synthesis of cystobactamide C, which paves
the way to the synthesis of further cystobactamide
variations.
Hans Knöll Institute, Jena
The Hans Knöll Institute (HKI) is a leading institute for
natural compound research. As an associated partner, it
provides the DZIF with natural compounds, particularly
fungi. A project is investigating the pharmacodynamics of
corallopyronin A, a natural product that has already been
successfully tested against the filariasis pathogen and is
undergoing preclinical evaluations. The HKI is largely responsible for its biosynthesis; the production was further
optimised in 2014.
Max Planck Institute for Informatics, Saarbrücken
At the Max Planck Institute for Informatics in Saarbrücken, data on hepatitis C patients who are undergoing
treatment with new antiviral agents, is being collected
as part of a DZIF project. Sequencing, analysis and interpretation of patient and viral genes, along with other
parameters, will be used to evaluate the course of treatment. In Saarbrücken, the analysis results are being used
to further develop an online-based tool, the so-called
Geno2pheno[HCV]. The analysis results are therefore
freely accessible online, and can be used to support decisions for personalised treatment.
Robert Koch Institute, Berlin
(DZIF member since June 2015)
The DZIF and the Robert Koch Institute (RKI) collaborate in
many areas. A few examples: In the research field “Emerging
Infections”, the RKI is supporting strategic partnerships between research establishments, hospitals and pharmaceutical companies. In clinical trials, they are jointly developing
clinical guidelines. The DZIF has access to the RKI’s new databank “HIOBs” for its HIV research; the software has been
optimised and is now being implemented at the partner sites.
University Medical Center Freiburg
In a project with the University Medical Center Freiburg
on infections of the immunocompromised host, scientists
are looking to find genetic factors associated with increased susceptibility to infection. They intend to find biomarkers that allow better infection control, and are concentrating on fungal infections in immunocompromised
patients.
A second DZIF project is investigating the more targeted use of antibiotics (see also Charité). In 2014, a pilot
project impressively showed that antibiotic stewardship
(ABS) strategies can be implemented successfully. In an
intensive ABS programme in internal medicine at the
University Medical Center Freiburg, the use of important
broad spectrum antibiotics was reduced by approximately
30 percent in one year. The programme in Freiburg aimed
at reducing the use of cephalosporins and fluoroquinolones while encouraging the use of penicillin derivatives.
COLLABORATIONS
37
COLLABORATIONS
38
Collaborations with scientific institutions and industry
University of Münster
The University of Münster is partner in a project aimed
at developing new treatment strategies against gastrointestinal infections. In many cases, the commonly used
antibiotics harm the normal gut flora and can lead to complications. In Münster, the scientists are working on preventing
the complications associated with EHEC.
A second project is working on hospital pathogens, particularly multidrug-resistant Staphylococcus aureus in the
nasal region. Here, new lytic phage proteins for targeted
treatment are being investigated. Their efficiency and
specificity will be analysed in Münster.
MMV – Medicines for Malaria Venture, Geneva
(Switzerland)
An MMV portfolio substance is being clinically tested for
chemoprevention of Malaria tropica, using a human malaria infection model developed by DZIF colleagues in
Tübingen.
Myr GmbH, Burgwedel
Together with the University of Heidelberg, an active agent
(Myrcludex B) is being developed that can prevent hepatitis
B viruses from penetrating into cells, and could potentially
be used to prevent hepatitis B and D infections. Myr GmbH
is coordinating the entire project and overseeing the clinical
trial.
Collaborations with industry
Hyglos GmbH, Bernried
Hyglos GmbH and a consortium funded by the DZIF are
collaborating to produce and preclinically develop phage
lytic protein HY-133 (see University of Münster). They
are planning joint early-stage clinical development for
nasal decolonisation of Staphylococcus aureus.
ImevaX GmbH, Munich
The DZIF is funding a research group led by Prof Markus
Gerhard from the Technische Universität München in the
field of preclinical and early-stage clinical testing of the
Helicobacter pylori vaccine candidate IMX-101. Together
with other funders, the group founded a spin-off company
from the university, ImevaX GmbH.
Juno Therapeutics GmbH, Göttingen
Juno Therapeutics, formerly Stage Cell Therapeutics, is
collaborating and exploitation partner of the research
group led by Prof Dirk Busch, Technische Universität
München, working in the field of GMP quality-assured
production of central memory T cells for treatment of infections and cancer. The DZIF is funding the group led by
Prof Busch.
Sanaria Inc., Rockville (USA)
At the DZIF partner site Tübingen, scientists are developing a human malaria infection model. Here, the disease is
induced under controlled conditions in order to test new
active agents. Sanaria Inc. in Rockville, USA, produces malaria parasites in GMP quality for immunisation purposes,
which fulfil all the criteria for drug approval.
4SC Discovery GmbH, Martinsried
In the DZIF research field “Malaria”, a candidate antimalarial has gone into preclinical development. SC83288
is being tested as an inhibitor in animal models, and is
being further developed in close collaboration with the
company 4SC, which also produces the active agent.
DZG
39
DZG
German Health Research Centres
In focus at the DZG: combatting widespread diseases more effectively.
The main objective of the German government’s
health research programme is to develop more effective ways to combat widespread diseases. The groundwork for this has been laid at federal and state levels
with the establishment of German Health Research
Centres (DZG) as long-term, equal partnerships
between non-university research institutes and universities with medical centres.
These German Health Research Centres pool all of their
existing expertise, thereby greatly helping to close knowledge gaps and improve prevention, diagnosis and therapy
of their respective diseases. The research policy ensures
close collaboration between basic research and clinical research, always specifically oriented on the indications and
the patients’ needs. Close networking and the expansion
of existing research structures will allow faster transfer of
research results into clinical practice (translation).
The strategic cooperation of leading scientists in the
German Health Research Centres promotes Germany to
a high-ranking scientific location and increases its attractiveness to young scientists in Germany and around the
world.
2009 saw the foundation of the “German Centre for
Neurodegenerative Diseases” and the “German Centre
for Diabetes Research”. Alongside DZIF, the “German
Center for Cardiovascular Research”, the “German
Consortium for Translational Cancer Research” and the
“German Center for Lung Research” were launched in
2012.
From the outset, the six German Health Research
Centres have collaborated closely in order to share their
findings and exploit synergies.
40
Organisation and bodies
Structure of DZIF
General Assembly
FACTS AND FIGURES
The General Assembly is the central decision-making organ of DZIF. It comprises representatives of the member research establishments
of the DZIF. The General Assembly elects the members of the Executive Board and the Executive Director, and decides on the allocation of
funds to the research fields and infrastructures (TTUs and TIs).
Commission of Funding Authorities
Executive Board
Scientific Advisory Board
The Commission of Funding Authorities is
made up of the Federal Government and
respective states (Länder) and decides on
important matters of finance, organisation and personnel. The Executive Board
and the Managing Director report to the
Commission on all funding measures.
The Executive Board represents the
DZIF externally. It implements the
resolutions and tasks assigned by the
General Assembly and is responsible for
routine administrative affairs.
The association is supported by the
Scientific Advisory Board consisting of
internationally renowned experts from
the field of infection research. The Scientific Advisory Board advises the Executive
Board and General Assembly on all
scientific and programme-related matters.
Main Office
Internal Advisory Board
The members of the Internal Council are
DZIF scientists representing all areas and
locations of the centre. The council
advises the Executive Board on all scientific, programme-related and technical
matters and performs representative
duties.
The Main Office is located in Braunschweig and supports the Executive
Board in its work. Its duties include
organising research initiatives and
coordinating DZIF’s press and public
relations activities.
Thematic Translational Units (TTUs)
Translational Infrastructures (TIs)
The Thematic Translational Units bundle the research of the centre.
Each unit is dedicated to one pathogen or to one specific problem in
infection research.
Strategically aligned translational infection research requires
modern infrastructures. These are provided in the form of the
Translational Infrastructures, and can be used by all DZIF members.
Emerging Infections
Tuberculosis
Product Development Unit
Clinical Trial Unit
Malaria
HIV
African Partner Institutions
Biobanking
Hepatitis
Gastrointestinal Infections
Infections of the immunocompromised Host
Healthcare-associated and
Antibiotic-resistant bacterial
Infections
Natural Compound Library
Bioinformatics
Novel Antiinfectives
DZIF Academy
Partner Sites
DZIF conducts its research in 35 research establishments at seven locations throughout Germany. For each site, two scientists are appointed to coordinate the collaboration and to advise the Main Office. Various external research partners are also involved in DZIF projects.
Bonn-Cologne
Gießen-Marburg-Langen
Hamburg-Lübeck-Borstel
Hannover-Braunschweig
Heidelberg
Munich
Tübingen
Associated Partners
41
Central bodies
Executive Board
> Prof Dr M. Krönke, Universität und Universitäts klinikum Köln (Chair)
> Prof Dr U. Protzer, Technische Universität München
und Helmholtz Zentrum München (Vice Chair)
> Prof Dr D. Heinz, Helmholtz-Zentrum für Infektions forschung, Braunschweig
Managing Director
> Dr T. Jäger, DZIF e.V.
Scientific Advisory Board
> Prof Dr P. Alonso, WHO Global Malaria Programme, Switzerland
> Prof Dr R. Burger, Robert Koch Institut, Germany
> Prof Dr H. Feldmann, National Institute of Allergy
and Infectious Diseases, USA
> Prof Dr B. B. Finlay, University of British Columbia,
Canada
> Prof Dr A. Friedrich, Universitair Medisch Centrum
Groningen, Netherlands
> Prof Dr B. Kampmann (Chair), Imperial College London,
United Kingdom
> Prof Dr J.-M. Pawlotsky, Université de Paris XII, France
> Prof Dr C. Rooney, Baylor College of Medicine, USA
> Prof Dr H. J. Schmitt, Johannes Gutenberg-Universität
Mainz, Germany, and Pfizer Vaccines, France
> Prof Dr A. Telenti, The J. Craig Venter Institute, USA
> Prof Dr S. Ward, Liverpool School of Tropical Medicine,
United Kingdom
> Prof Dr R. G. Werner, Universität Tübingen, Germany
Internal Advisory Board
> Prof Dr I. Autenrieth, Universität und
Universitätsklinikum Tübingen
> Prof Dr K. Cichutek, Paul-Ehrlich-Institut, Langen
> Prof Dr C. Drosten, Universität und
Universitätsklinikum Bonn
> Prof Dr M. Hoelscher, Ludwigs-Maximilians Universität München and Klinikum der Universität
München
> Prof Dr R. Horstmann, Bernhard-Nocht-Institut
für Tropenmedizin, Hamburg (Vice Chair)
> Prof Dr H.-G. Kräusslich, Universität und
Universitätsklinikum Heidelberg (Chair)
> Prof Dr T. Schulz, Medizinische Hochschule
Hannover
> Prof Dr T. Welte, Medizinische Hochschule
Hannover
42
Partner sites and member establishments
Hamburg - Lübeck - Borstel
Hannover - Braunschweig
Bonn - Cologne
Gießen - Marburg - Langen
Heidelberg
Tübingen
Munich
43
Partner sites and member establishments
Germany-wide
infection research
FACTS AND FIGURES
Baden-Württemberg
Heidelberg is responsible for coordinating the TTU HIV at the DZIF.
In order to control HIV infections,
DZIF researchers at this location
research factors of the innate immune system and identify sites in
the DNA into which the viral DNA
can become integrated. Alongside
HIV, Heidelberg co-coordinates
the TTUs Hepatitis, Malaria and Infections of the Immunocompromised
Host. The Heidelberg scientists also
coordinate the DZIF-wide translational infrastructure Biobanking,
with focus on establishing tissue
banks.
Heidelberg
Spokesperson: Klaus Heeg (Heidel-
Tübingen has taken over the coordinating role at the DZIF for Malaria
and Healthcare-associated and Antibiotic-resistant bacterial Infections,
and co-coordinators of Gastrointestinal Infections and Novel Antiinfectives work at this location. The main
focus in Tübingen is on translating
research results into medicine and
vaccine development as well as on
infection models and epidemiology. Regarding infections caused by
antibiotic-resistant, bacterial pathogens, the focus is on improving
diagnosis and therapy of multiresistant pathogens such as methicillinresistant Staphylococci (MRSA) and
multiresistant gram-negative pathogens (e.g. so-called ESBLs).
berg University Hospital)
Establishments: German Cancer
Research Center in the Helmholtz
Association, Heidelberg University,
Heidelberg University Hospital
TTU coordination:
• Hepatitis (co-coordination)
• HIV (coordination)
• Infections of the Immunocompromised Host (co-coordination)
• Malaria (co-coordination)
TI coordination:
• Biobanking (coordination)
Tübingen
Spokesperson: Prof Dr Ingo Autenrieth (University of Tübingen)
Establishments: University of
Tübingen, Max Planck Institute for
Developmental Biology, University
Hospital Tübingen
TTU coordination:
• Gastrointestinal Infections
(co-coordination)
• Healthcare-associated and
Antibiotic-resistant bacterial
Infections (coordination)
• Malaria (coordination)
• Novel Antiinfectives
(co-coordination)
44
Bavaria
Hamburg/Schleswig-Holstein
Hessen
The scientists of the Munich DZIF
establishments have special focus
on immune control of infections and
the development of novel therapies.
Pathogen-specific immunotherapies
(prophylactic or therapeutic) aim at
strengthening the body’s natural defence system so that it can control
specific infectious diseases more effectively or even avoid them entirely.
Other focuses in Munich are Gastrointestinal Infections, HIV, Hepatitis and
Tuberculosis.
The Hamburg-Lübeck-Borstel site
combines a unique collection of expertise and infrastructure for studying
infectious diseases and emerging infections of national and worldwide relevance. It is involved in clinical, entomological and virological studies. It is
the DZIF base for medical chemistry,
for active agent development as well
as for the epidemiology of malaria and
translational studies on tuberculosis
and hepatitis. The TI African Partner
Institutions is coordinated from here.
Munich
Spokesperson: Prof Dr Dirk Busch
(Technische Universität München)
Establishments: Helmholtz Zentrum München – German Research
Center for Environmental Health,
Bundeswehr Institute of Microbiology, Klinikum der Universität München, Klinikum rechts der Isar der
Technischen Universität München,
Ludwig-Maximilians-Universität
München, Technische Universität
München
TTU coordination:
•Gastrointestinal Infections
(co-coordination)
•Hepatitis (co-coordination)
•HIV (co-coordination)
•Infections of the Immunocom-
promised Host (coordination)
• Tuberculosis (co-coordination)
TI coordination:
• Biobanking (co-coordination)
• DZIF Academy (coordination)
Hamburg - Lübeck - Borstel
Spokesperson: Prof Dr Rolf Horstmann (Bernhard Nocht Institute for
Tropical Medicine)
Establishments: Bernhard Nocht
Institute for Tropical Medicine in
the Leibniz Association, Research
Center Borstel – Leibniz-Center for
Medicine and Biosciences, FriedrichLoeffler-Institut (member since
June 2015), Heinrich Pette Institute
– Leibniz Institute for Experimental
Virology, Universität Hamburg,
University Medical Center HamburgEppendorf, Universität zu Lübeck
TTU coordination:
•Emerging Infections
(co-coordination)
•Malaria (co-coordination)
• Tuberculosis (coordination)
TI coordination:
•African Partner Institutions
(coordination)
In Gießen-Marburg-Langen, DZIF
researchers identify new active
agents and vaccines and produce
them in quality-assured production
processes for scientific and industrial
partners. Research activities are concentrated on developing strategies
for combatting new or re-emerging
infectious diseases in order to contain outbreaks of new pathogens, for
example by quick, effective action and
rapid vaccine development. Marburg
focus on viral pathogens, while Gießen
concentrate on bacteria and resistance to antibiotics.
Gießen - Marburg - Langen
Spokesperson: Prof Dr Trinad
Chakraborty (Giessen University)
Establishments: Giessen University, Paul Ehrlich Institute Langen,
Philipps-Universität Marburg,
Mittelhessen University of Applied
Sciences
TTU coordination:
• Emerging Infections (coordination)
• Healthcare-associated and Anti-
biotic-resistant bacterial Infections (co-coordination)
TI coordination:
•Bioinformatics (coordination)
•Product Development Unit
(coordination)
45
Seven partner institutes collaborate within DZIF at the HannoverBraunschweig location. The TTUs
Hepatitis and Gastrointestinal Infections are coordinated from here. The
scientists here want, among other
things, to improve access to hepatitis therapies and are researching
on new diagnostic markers for the
course of infection and therapy. Also
in the researchers’ sights are new
pathogen-specific medicines against
pathogens such as EHEC, Helicobacter
pylori or salmonellae. This location
is coordinating the establishment of
the Natural Compound Library, which
is available to all DZIF researchers in
the search for new medicines.
Hannover - Braunschweig
Spokesperson: Prof Dr Sebastian
Suerbaum (Hannover Medical School)
Establishments: Helmholtz Centre
for Infection Research, Braunschweig,
Leibniz Institute DSMZ – German
Collection of Microorganisms and Cell
Cultures, Hannover Medical School,
Robert Koch Institute (Member since
June 2015) University of Veterinary
Medicine Hannover, Foundation,
Technische Universität Braunschweig,
TWINCORE – Centre for Experimental and Clinical Infection Research
TTU coordination:
• Gastrointestinal Infections
(coordination)
• Hepatitis (coordination)
• Infections of the Immunocom promised Host (co-coordination)
North Rhine-Westphalia
TI coordination:
• Natural Compound Library
(coordination)
• Biobanking (co-coordination)
• Bioinformatics (coordination)
Bonn-Cologne coordinates the TTU
Novel Antiinfectives. The DZIF researchers are also researching into
faster and more efficient methods
for characterising unknown viral pathogens. Unique in Germany are the
patient cohorts for HIV and HCV infections as well as HIV/HCV co-infections. In HIV research, researchers are
bringing into translation gene-therapy–based strategies for the control
and prophylaxis of these infections.
This location coordinates the DZIF
Clinical Trial Unit.
Bonn - Cologne
Spokesperson: Prof Dr Achim
Hörauf (University of Bonn)
Establishments: Federal Institute
for Drugs and Medical Devices
(BfArM/ Member since June 2015),
University of Bonn, University Hospital Bonn, University of Cologne,
University Hospital Cologne
TTU coordination:
• Emerging Infections
(co-coordination)
• HIV (co-coordination)
• Healthcare-associated and Anti-
biotic-resistant bacterial
Infections (co-coordination)
•Novel Antiinfectives (coordination)
TI coordination:
• Clinical Trial Units (coordination)
FACTS AND FIGURES
Lower Saxony
46
Finance
DZIF financial data 2014
2014 expenditure in Euros
By partner site
Associated Partners
949,832
Gießen-Marburg-Langen
Hannover-Braunschweig
4,034,046
FACTS AND FIGURES
1,626,759
Heidelberg
2,938,715
Hamburg-Lübeck-Borstel
2,901,904
Munich
2,727,883
Bonn-Cologne
Tübingen
2,504,326
2,144,753
By type of expenditure
Material Expenses
5,790,516
Investments
375,635
Personnel
13,662,068
47
Field of work
Emerging infections
Tuberculosis
Grants from government and Länder in Euros
Euros
1,805,260
775,428
Land
Euros
Baden-Württemberg
508,347
Bavaria
269,614
Malaria
1,796,459
Hamburg
167,361
HIV
1,362,739
Hessen
110,850
Hepatitis
1,807,037
Lower Saxony
403,405
North Rhine-Westphalia
250,433
Infections in the immunocompromised Host 2,034,029
Schleswig-Holstein
122,829
Healthcare-associated and Antibioticresistant bacterial Infections
1,097,482
Financial Contributions from
Associated Partners
Novel Antiinfectives
2,233,992
Federal Government
17,908,381
Total
19,828,218
Gastrointestinal Infections
903,178
Product Development Unit
586,627
Clinical Trial Unit
275,461
African Partner Institutions
272,704
Biobanking
727,185
Natural Compound Library
396,074
Bioinformatics
345,801
DZIF Academy
1,630,624
Administration
1,778,137
Total
19,828,218
The German Center for Infection Research expenditure
in 2014 was around 19.8 million Euros.
129 collaborative projects and 52 stipends were
funded within DZIF in 2014. The majority of funding
came from the Federal Government (90 %) and from
Länder funds (10 %). Only departmental research
projects of the federal R&D institutions were fully
funded by Germany’s Federal Ministries. Funding
management at the Helmholtz Centre for Infection Research in Braunschweig forwards the federal funds to
the DZIF partner institutes to support their projects.
Expenditure was reported by the partners in their
interim statements for 2014 and audited by Funding
Management.
87,000
FACTS AND FIGURES
By field of work
48
Personnel and awards
Employees of DZIF
Full-time equivalent by professional group
Professor
Junior Group Head
4.5
13.3
Physician
Other
25.0
59.1
Total: 266.1
FACTS AND FIGURES
Postdoc
74.4
TA/Study Nurse
55.6
PhD/MD Student
34.1
Full-time equivalent corresponds to a full-time position in an entire fiscal year.
Number of employees by professional group and gender
Professional Groups
Men
Women
Total
Professor
6
2
8
Junior Group Head
13
5
18
Physician
17
27
44
Postdoc
52
90
142
PhD/MD Student
47
56
103
TA/Study Nurse
22
80
102
Other
27
49
76
Total
184
309
493
DZIF recruited 2014 six employees from abroad and assisted ten mothers
on their return from maternity leave.
49
Laureates
Awards
Prof Dr Ralf Bartenschlager
Heidelberg University
Thomson Reuters Selection:
Highly Cited Researchers 2014
Prof Dr Jonas Schmidt-Chanasit
Bernhard Nocht Institute for Tropical Medicine
Wissenschaftspreis „Klinische Virologie“ der Gesellschaft für Virologie und der Deutschen Vereinigung
zur Bekämpfung der Viruskrankheiten
Prof Dr Christoph Klein
Klinikum der Universität München
Hector Research Prize
Prof Dr Florian Klein
University Hospital Cologne/Rockefeller University
AIDS-Forschungspreis der Deutschen Gesellschaft
für Infektiologie (DGI)
Prof Dr Dr h.c. Christoph Lange
Research Center Borstel
“Society needs Science” Award by the Stifterverband
(Donors‘ Association for the Promotion of the Sciences and the Humanities in Germany
Dr Clara Lehmann
University Hospital Cologne
DGI-Förderpreis für Klinische Infektionsforschung
Dr Julie Lucifora
Helmholtz Zentrum München
European Young Investigator Award, EASL
Dr Konstantin Neumann
Klinikum rechts der Isar, Technische Universität
München
Gábor-Szász-Prize
Prof Dr Sebastian Suerbaum
Hannover Medical School
Election into the American Academy of
Microbiology
Prof Dr Stephan Urban
Heidelberg University
DZIF Prize for Translational Infection Research
Dr Christopher Weidenmaier
University of Tübingen
Förderpreis der DGHM
FACTS AND FIGURES
Awards and commendations
50
Publications
Scientific achievements 2014
In the following you will find a list of selected publications from 2014 (Impact Factor larger than 10).
See the complete list of DZIF publications on our website.
1. Alduina R, Gallo G, Renzone G, Weber
T, Scaloni A, Puglia AM (2014) Novel
Amycolatopsis balhimycina biochemical
abilities unveiled by proteomics. FEMS
Microbiol Lett, 351(2): 209-215
PUBLICATIONS
2. Allweiss L, Volz T, Lutgehetmann M,
Giersch K, Bornscheuer T, Lohse AW,
Petersen J, Ma H, Klumpp K, Fletcher SP,
Dandri M (2014) Immune cell responses
are not required to induce substantial hepatitis B virus antigen decline during pegylated
interferon-alpha administration. J Hepatol,
60(3): 500-507
3. Baize S, Pannetier D, Oestereich L,
Rieger T, Koivogui L, Magassouba N,
Soropogui B, Sow MS, Keita S, De Clerck
H, Tiffany A, Dominguez G, Loua M, Traore
A, Kolie M, Malano ER, Heleze E, Bocquin
A, Mely S, Raoul H, Caro V, Cadar D, Gabriel
M, Pahlmann M, Tappe D, Schmidt-Chanasit
J, Impouma B, Diallo AK, Formenty P, Van
Herp M, Gunther S (2014) Emergence of
Zaire Ebola virus disease in Guinea. N Engl J
Med, 371(15): 1418-1425
4. Baumann S, Herrmann J, Raju R,
Steinmetz H, Mohr KI, Huttel S, Harmrolfs
K, Stadler M, Muller R (2014) Cystobactamids: myxobacterial topoisomerase
inhibitors exhibiting potent antibacterial activity. Angew Chem Int Ed Engl, 53(52):
14605-14609
5. Berger C, Romero-Brey I, Radujkovic
D, Terreux R, Zayas M, Paul D, Harak C,
Hoppe S, Gao M, Penin F, Lohmann V,
Bartenschlager R (2014) Daclatasvir-like
inhibitors of NS5A block early biogenesis
of hepatitis C virus-induced membranous
replication factories, independent of RNA
replication. Gastroenterology, 147(5):
1094-1105.e1025
6. Bos KI, Harkins KM, Herbig A,
Coscolla M, Weber N, Comas I, Forrest
SA, Bryant JM, Harris SR, Schuenemann
VJ, Campbell TJ, Majander K, Wilbur AK,
Guichon RA, Wolfe Steadman DL, Cook
DC, Niemann S, Behr MA, Zumarraga M,
Bastida R, Huson D, Nieselt K, Young D,
Parkhill J, Buikstra JE, Gagneux S, Stone
AC, Krause J (2014) Pre-Columbian mycobacterial genomes reveal seals as a source
of New World human tuberculosis. Nature,
514(7523): 494-497
12. Giersch K, Helbig M, Volz T,
Allweiss L, Mancke LV, Lohse AW,
Polywka S, Pollok JM, Petersen J, Taylor
J, Dandri M, Lütgehetmann M (2014)
Persistent hepatitis D virus mono-infection
in humanized mice is efficiently converted
by hepatitis B virus to a productive coinfection. J Hepatol, 60(3): 538-544
7. Boztug K, Jarvinen PM, Salzer E, Racek
T, Monch S, Garncarz W, Gertz EM,
Schaffer AA, Antonopoulos A, Haslam
SM, Schieck L, Puchalka J, Diestelhorst
J, Appaswamy G, Lescoeur B, Giambruno R, Bigenzahn JW, Elling U, Pfeifer D,
Conde CD, Albert MH, Welte K, Brandes
G, Sherkat R, van der Werff Ten Bosch J,
Rezaei N, Etzioni A, Bellanne-Chantelot C,
Superti-Furga G (2014) JAGN1 deficiency
causes aberrant myeloid cell homeostasis and
congenital neutropenia. Nat Genet, 46(9):
1021-1027
13. Goubau D, Schlee M, Deddouche
S, Pruijssers AJ, Zillinger T, Goldeck M,
Schuberth C, Van der Veen AG, Fujimura T,
Rehwinkel J, Iskarpatyoti JA, Barchet W,
Ludwig J, Dermody TS, Hartmann G, Reis
e Sousa C (2014) Antiviral immunity via
RIG-I-mediated recognition of RNA bearing
5‘-diphosphates. Nature, 514(7522):
372-375
8. Diepold A, Wagner S (2014). Assembly
of the bacterial type III secretion machinery. FEMS Microbiol Rev, 38(4): 80222. doi: 10.1111/1574-6976.12061
9. Diethelm S, Teufel R, Kaysser L, Moore BS. (2014) A multitasking vanadium-
dependent chloroperoxidase as an inspiration
for the chemical synthesis of the merochlorins. Angew Chem Int Ed Engl, 53(41):
11023-6
10. Drosten C, Meyer B, Muller MA,
Corman VM, Al-Masri M, Hossain R,
Madani H, Sieberg A, Bosch BJ, Lattwein
E, Alhakeem RF, Assiri AM, Hajomar W,
Albarrak AM, Al-Tawfiq JA, Zumla AI,
Memish ZA (2014) Transmission of MERScoronavirus in household contacts. N Engl J
Med, 371(9): 828-835
11. Fackler OT, Murooka TT, Imle A,
Mempel TR , (2014) Adding new dimensions:
towards an integrative understanding of
HIV-1 spread. Nat Rev Microbiol, 12(8):
563-574. doi: 10.1038/nrmicro3309
14. Graef P, Buchholz VR, Stemberger
C, Flossdorf M, Henkel L, Schiemann M,
Drexler I, Hofer T, Riddell SR, Busch DH
(2014) Serial transfer of single-cell-derived
immunocompetence reveals stemness of
CD8(+) central memory T cells. Immunity,
41(1): 116-126
15. Gronbach K, Flade I, Holst O, Lindner
B, Ruscheweyh HJ, Wittmann A, Menz S,
Schwiertz A, Adam P, Stecher B, Josenhans
C, Suerbaum S, Gruber AD, Kulik A, Huson
D, Autenrieth IB, Frick JS (2014) Endo-
toxicity of lipopolysaccharide as a determinant
of T-cell-mediated colitis induction in mice.
Gastroenterology, 146(3): 765-775
16. Heidrich B, Yurdaydin C, Kabacam G,
Ratsch BA, Zachou K, Bremer B, Dalekos
GN, Erhardt A, Tabak F, Yalcin K, Gurel S,
Zeuzem S, Cornberg M, Bock CT, Manns
MP, Wedemeyer H (2014) Late HDV RNA
relapse after peginterferon alpha-based
therapy of chronic hepatitis delta. Hepatology, 60(1): 87-97
17. Heyckendorf J, Olaru ID, Ruhwald M,
Lange C (2014) Getting personal
perspectives on individualized treatment
duration in multidrug-resistant and 51
18. Hösel M, Lucifora J, Michler T,
Holz G, Gruffaz M, Stahnke S, Zoulim F,
Durantel D, Heikenwalder M, Nierhoff D,
Millet R, Salvetti A, Protzer U, Büning H
(2014) Hepatitis B virus infection enhances
susceptibility toward adeno-associated
viral vector transduction in vitro and in vivo.
Hepatology, 59(6): 2110-2120
19. Jansen R, Sood S, Huch V, Kunze B,
Stadler M, Muller R (2014) Pyrronazols,
metabolites from the myxobacteria Nannocystis pusilla and N. exedens, are unusual chlorinated pyrone-oxazole-pyrroles.
J Nat Prod, 77(2): 320-326
20. Kaufmann SH, Lange C, Rao M,
Balaji KN, Lotze M, Schito M, Zumla AI,
Maeurer M (2014) Progress in tuberculosis vaccine development and host-directed
therapies--a state of the art review. Lancet
Respir Med, 2(4): 301-320
21. Klein F, Nogueira L, Nishimura Y,
Phad G, West AP Jr, Halper-Stromberg
A, Horwitz JA, Gazumyan A, Liu C,
Eisenreich TR, Lehmann C, Fätkenheuer
G, Williams C, Shingai M, Martin MA,
Bjorkman PJ, Seaman MS, Zolla-Pazner
S, Karlsson Hedestam GB, Nussenzweig
MC (2014) Enhanced HIV-1 immuno-
therapy by commonly arising antibodies
that target virus escape variants, J Exp
Med, 211(12): 2361-72.
22. Kokordelis P, Kramer B, Korner C,
Boesecke C, Voigt E, Ingiliz P, Glassner
A, Eisenhardt M, Wolter F, Kaczmarek D,
Nischalke HD, Rockstroh JK, Spengler
U, Nattermann J (2014) An effective
interferon-gamma-mediated inhibition
of hepatitis C virus replication by natural
killer cells is associated with spontaneous
clearance of acute hepatitis C in human
immunodeficiency virus-positive patients.
Hepatology, 59(3): 814-827
23. König A, Döring B, Mohr C, Geipel
A, Geyer J, Glebe D (2014) Kinetics of the
bile acid transporter and hepatitis B virus
receptor Na+/taurocholate cotransporting
polypeptide (NTCP) in hepatocytes. J Hepatol, 61(4): 867-875
24. Kreijtz JH, Goeijenbier M, Moesker
FM, van den Dries L, Goeijenbier S, De
Gruyter HL, Lehmann MH, Mutsert G, van
de Vijver DA, Volz A, Fouchier RA, van Gorp
EC, Rimmelzwaan GF, Sutter G, Osterhaus
AD (2014) Safety and immunogenicity of a
modified-vaccinia-virus-Ankara-based influenza
A H5N1 vaccine: a randomised, double-blind
phase 1/2a clinical trial. Lancet Infect Dis,
14(12): 1196-1207
25. Kreuels B, Wichmann D, Emmerich
P, Schmidt-Chanasit J, de Heer G, Kluge
S, Sow A, Renne T, Gunther S, Lohse AW,
Addo MM, Schmiedel S (2014) A case of
severe Ebola virus infection complicated by
gram-negative septicemia. N Engl J Med,
371(25): 2394-2401
26. Krumm SA, Yan D, Hovingh ES, Evers
TJ, Enkirch T, Reddy GP, Sun A, Saindane
MT, Arrendale RF, Painter G, Liotta DC,
Natchus MG, von Messling V, Plemper
RK (2014) An orally available, small-
molecule polymerase inhibitor shows efficacy against a lethal morbillivirus infection in a large animal model. Sci
Transl Med, 6(232): 232ra252
27. Liehl P, Zuzarte-Luís V, Chan J, Zillinger
T, Baptista F, Carapau D, Konert M, Hanson
KK, Carret C, Lassnig C, Müller M, Kalinke
U, Saeed M, Chora AF, Golenbock DT, Strobl
B, Prudêncio M, Coelho LP, Kappe SH,
Superti-Furga G, Pichlmair A, Vigário AM,
Rice CM, Fitzgerald KA, Barchet W, Mota
MM (2014) Host-cell sensors for Plasmodium
activate innate immunity against liver-stage
infection. Nat Med, 20(1): 47–53
28. Lu C, Maurer CK, Kirsch B,
Steinbach A, Hartmann RW (2014)
Overcoming the Unexpected Functional
Inversion of a PqsR Antagonist in Pseudomonas
aeruginosa: An In Vivo Potent Antivirulence
Agent Targeting pqs Quorum Sensing.
Angew Chem Int Ed, 53: 1109–1112
29. Lucifora J, Xia Y, Reisinger F, Zhang
K, Stadler D, Cheng X, Sprinzl MF,
Koppensteiner H, Makowska Z, Volz T,
Remouchamps C, Chou WM, Thasler WE,
Huser N, Durantel D, Liang TJ, Munk C,
Heim MH, Browning JL, Dejardin E, Dandri
M, Schindler M, Heikenwalder M, Protzer
U (2014) Specific and nonhepatotoxic degradation of nuclear hepatitis B virus cccDNA.
Science, 343(6176): 1221-1228
30. Lusic M, Giacca M (2014) Ground
control to Major Tom: „prepare for HIV landing“, Cell Host Microbe, 16(5): 557-9.
doi: 10.1016/j.chom.2014.10.012
31. Madan V, Paul D, Lohmann V, Bartenschlager R (2014) Inhibition of HCV
replication by cyclophilin antagonists is linked
to replication fitness and occurs by inhibition
of membranous web formation. Gastroenterology, 146(5): 1361-1372.e1361-1369
32. Manns MP, Vierling JM, Bacon BR,
Bruno S, Shibolet O, Baruch Y, Marcellin
P, Caro L, Howe AY, Fandozzi C, Gress
J, Gilbert CL, Shaw PM, Cooreman MP,
Robertson MN, Hwang P, Dutko FJ, Wahl
J, Mobashery N (2014) The Combination
of MK-5172, Peginterferon, and Ribavirin Is
Effective in Treatment-Naive Patients With
Hepatitis C Virus Genotype 1 Infection
Without Cirrhosis. Gastroenterology,
147(2): 366-376.e6
33. Manns MP, Pol S, Jacobson IM,
Marcellin P, Gordon SC, Peng CY, Chang
TT, Everson GT, Heo J, Gerken G, Yoffe B,
Towner W, Bourliere M, Metivier S, Chu
CJ, Sievert W, Bronowicki JP, Thabut D,
Lee YJ, Kao JH, McPhee F, Kopit J, Mendez
P, Linaberry M, Hughes E, Noviello S, on
behalf of the HALLMARK-DUAL
PUBLICATIONS
extensively drug-resistant tuberculosis. Am
J Respir Crit Care Med, 190(4): 374-383
52
Publications
Study Team (2014) All-oral daclatasvir plus
asunaprevir for hepatitis C virus genotype 1b:
a multinational, phase 3, multicohort study.
Lancet, 384(9954): 1597-1605
PUBLICATIONS
34. Ni Y, Lempp FA, Mehrle S, Nkongolo
S, Kaufman C, Falth M, Stindt J, Koniger C,
Nassal M, Kubitz R, Sultmann H, Urban S
(2014) Hepatitis B and D viruses exploit sodium taurocholate co-transporting polypeptide
for species-specific entry into hepatocytes.
Gastroenterology, 146(4): 1070-1083
35. Nkongolo S, Ni Y, Lempp FA,
Kaufman C, Lindner T, Esser-Nobis K,
Lohmann V, Mier W, Mehrle S, Urban S
(2014) Cyclosporin A inhibits hepatitis B
and hepatitis D virus entry by cyclophilinindependent interference with the NTCP
receptor. J Hepatol, 60(4): 723-731
36. Oehler N, Volz T, Bhadra OD, Kah
J, Allweiss L, Giersch K, Bierwolf J,
Riecken K, Pollok JM, Lohse AW, Fehse
B, Petersen J, Urban S, Lutgehetmann
M, Heeren J, Dandri M (2014) Binding
of hepatitis B virus to its cellular receptor
alters the expression profile of genes of bile
acid metabolism. Hepatology, 60(5):
1483-1493
37. Peiffer KH, Akhras S, Himmelsbach
K, Hassemer M, Finkernagel M, Carra
G, Nuebling M, Chudy M, Niekamp H,
Glebe D, Sarrazin C, Zeuzem S, Hildt E
(2014) Intracellular accumulation of subviral HBsAg particles and diminished Nrf2
activation in HBV genotype G expressing
cells lead to an increased ROI level. J Hepatol, 62(4): 791-798
Mfinanga E, Said K, Haraka F, Rachow A,
Saathoff E, Mpina M, Jugheli L, Lwilla F,
Marais BJ, Hoelscher M, Daubenberger
C, Reither K, Geldmacher C (2014)
Assessment of the novel T-cell activation
marker-tuberculosis assay for diagnosis of
active tuberculosis in children: a prospective
proof-of-concept study. Lancet Infect Dis,
14(10): 931-938
40. Schaberle TF, Lohr F, Schmitz A,
Konig GM (2014) Antibiotics from myxobacteria. Nat. Prod. Rep., 31(7): 953-972
41. Schubert D, Bode C, Kenefeck R, Hou
TZ, Wing JB, Kennedy A, Bulashevska A,
Petersen BS (2014) Autosomal dominant
immune dysregulation syndrome in humans
with CTLA4 mutations. Nat Med, 20(12):
1410-6. doi: 10.1038/nm.3746
42. Sester M, van Leth F, Bruchfeld J,
Bumbacea D, Cirillo DM, Dilektasli AG,
Dominguez J, Duarte R, Ernst M, Eyuboglu
FO, Gerogianni I, Girardi E, Goletti D,
Janssens JP, Julander I, Lange B, Latorre
I, Losi M, Markova R, Matteelli A, Milburn
H, Ravn P, Scholman T, Soccal PM, Straub
M, Wagner D, Wolf T, Yalcin A, Lange C
(2014) Risk assessment of tuberculosis in
immunocompromised patients. A TBNET
study. Am J Respir Crit Care Med,
190(10): 1168-1176
43. Surup F, Viehrig K, Mohr KI, Herrmann
J, Jansen R, Muller R (2014) Disciformycins
A and B: 12-membered macrolide glycoside
antibiotics from the myxobacterium Pyxidicoccus fallax active against multiresistant staphylococci. Angew Chem Int Ed
Engl, 53(49): 13588-13591
38. Pischke S, Behrendt P, Manns MP,
Wedemeyer H (2014) HEV-associated
cryoglobulinaemia and extrahepatic manifestations of hepatitis E. Lancet Infect Dis,
14(8): 678-679
44. Tacconelli E, Kern WV (2014) New
antibiotics for skin and skin-structure
infections. Lancet Infectious Diseases,
14(8): 659-661
39. Portevin D, Moukambi F, Clowes
P, Bauer A, Chachage M, Ntinginya NE,
45. Teufel R, Kaysser L, Villaume MT,
Diethelm S, Carbullido MK, Baran PS,
Moore BS. (2014) One-pot enzymatic
synthesis of merochlorin A and B. Angew
Chem Int Ed Engl, 53(41): 11019-22
46. Theron G, Zijenah L, Chanda D,
Clowes P, Rachow A, Lesosky M, Bara W,
Mungofa S, Pai M, Hoelscher M, Dowdy
D, Pym A, Mwaba P, Mason P, Peter J,
Dheda K (2014) Feasibility, accuracy, and
clinical effect of point-of-care Xpert MTB/
RIF testing for tuberculosis in primary-care
settings in Africa: a multicentre, randomised, controlled trial. Lancet, 383(9915):
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53
Bernhard Nocht Institute for Tropical Medicine
Robert Koch Institute*
Bundeswehr Institute of Microbiology
Technische Universität Braunschweig
Federal Institute for Drugs and Medical Devices*
Technische Universität München
Friedrich-Loeffler–Institut*
TWINCORE - Centre for Experimental and
Clinical Infection Research
German Cancer Research Center
Giessen University
Hannover Medical School
Heidelberg University
Heidelberg University Hospital
Heinrich Pette Institute–Leibniz Institute for
Experimental Virology
Universität Hamburg
Universität zu Lübeck
University of Bonn
University of Cologne
University of Tübingen
University of Veterinary Medicine Hannover, Foundation
Helmholtz Centre for Infection Research
University Hospital Bonn
Helmholtz Zentrum München–German Research Center
for Environmental Health
University Hospital Cologne
Klinikum der Universität München
University Hospital Tübingen
University Medical Center Hamburg-Eppendorf
Klinikum rechts der Isar der Technischen
Universität München
Leibniz Institute DSMZ–German Collection of
Microorganisms and Cell Cultures
Ludwig-Maximilians-Universität München
Max Planck Institute for Developmental Biology
Mittelhessen University of Applied Sciences
Paul-Ehrlich-Institut
Philipps-Universität Marburg
Research Center Borstel–Leibniz-Center
for Medicine and Bioscience
* Member establishment since June 2015
MEMBER ESTABLISHMENTS
Member establishments of
the German Center for
Infection Research
54
Imprint
German Center for Infection Research (DZIF e.V.)
Main Office
Inhoffenstraße 7
D-38124 Braunschweig
T +49 (0)531-61 81-11 52
F +49 (0)531-61 81-11 53
[email protected]
www.dzif.de
Project coordination: DZIF Press Office
Text: Dr Heidrun Riehl-Halen, Medizinkontext, and DZIF Press Office
English translation: Julia Kyambi
Photos: Title: Alix Poulot, University of Lyon | p. 3: DZIF/scienceRELATIONS | p. 4: Hallbauer
IMPRINT
+ Fioretti | p. 6: Günter Fröschl | p. 7 (above): Robert Wollny | p. 7 (below): DZIF/scienceRELATIONS | p. 9 (above): Reprinted by permission from: Merker et al. NatGen 47, 242-249 (2015)
doi:10.1038/ng.3195 | p. 9 (centre): DZIF/scienceRELATIONS | p. 9 (below): Research Center
Borstel | p. 10: Bernhard Nocht Institute | p. 11 (above): cdc/James Gathany I p. 11 (below):
DZIF/scienceRELATIONS | p. 12: Heidelberg University Hospital | p. 13 (above): Reprinted
by permission from Macmillan Publishers LTD: Nature 517, 505-508 (22 January 2015); doi:
10.1038/nature13838 | p. 13 (below): DZIF/scienceRELATIONS | p. 14: Alix Poulot, University
of Lyon | p. 15 (below): DZIF/scienceRELATIONS | p. 17 (below): DZIF/scienceRELATIONS |
p. 18: Dr. von Hauner Children´s Hospital | p. 19 (below left): cdc/Dr. Paul M. Feorino | p. 19
(below right): DZIF/scienceRELATIONS | p. 20/21: Katrina Friese | p.21 (below): DZIF/scienceRELATIONS | p. 22: Barbara Frommann/University of Bonn | p. 23 (above + centre): HZI/M.
Rohde | p. 23 (below): DZIF/scienceRELATIONS | p. 24: Paul-Ehrlich-Institut | p. 25: MedizinFotoKöln | p. 26: Bernhard Nocht Institute | p. 27 (above): HIPS/Bellhäuser | p. 27 (below):
Helmholtz Institute for Pharmaceutical Research Saarland/Saarland University | p. 28 (above):
Helmholtz Zentrum München | p. 28 (below): Heidelberg University Hospital | p. 29 (above):
iStock | p. 29 (below 1): Helmholtz Centre for Infection Research | p. 29 (below 2): Universitätsklinikum Gießen und Marburg | p. 30: DZIF/scienceRELATIONS | p. 31: cdc/Frederick A.
Murphy | p. 32: (top down): Research Center Borstel; DZIF/scienceRELATIONS; Heidelberg
University Hospital | p. 33: (above left): DZIF | p. 33 (above right): Research Center Borstel/
Pukall | p. 33 (below): istock/pixhook | p. 34: DZIF/factum GmbH | p. 35 (above): Till Budde |
p. 35 (centre): Hallbauer + Fioretti | p. 35 (below): DZIF/scienceRELATIONS | p. 36/39: DZIF/
scienceRELATIONS
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Bayerisches Staatsministerium für
Wissenschaft, Forschung und Kunst
German Center for Infection Research (DZIF e.V.)
Main Office
Inhoffenstraße 7
D-38124 Braunschweig
T +49 (0)531-61 81-11 52
F +49 (0)531-61 81-11 53
[email protected]
www.dzif.de
© August 2015