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Translational Research
Host-Pathogen Interactions
FACULTÉ DE MÉDECINE
Microbiology at the Medical Faculty of the University of Geneva
Microbes have always accompanied human beings either by positively influencing our health
through stimulation of the immune system and providing essential nutrients, such as certain
vitamins, or by causing various diseases. Although several diseases can now be treated
effectively or are even on the point of being eradicated, some infectious pathogens persist or
reappear in the headlines and new emergent diseases threaten our health. The rapid
development of medicine has increased our life expectancy and quality of life considerably.
However, some of the treatments themselves, together with an aging population, constitute
new challenges as patients become more susceptible to infections. Global trends such as rapid,
mass long-distance travel and climate change greatly influence the steadily changing picture
of infectious diseases. Moreover, the appearance of multi- and fully-resistant pathogens poses
serious challenges to treatment and is of particular concern in long-lasting persistent infections
which represent a heavy burden to the individual and society.
It is for these reasons that research in microbiology at the Faculty of Medicine of the University
of Geneva is very broad, ranging from basic to clinical research and diagnostics. The
microorganisms studied in the different contexts are very diverse; several different bacteria,
eight classes of viruses, two apicomplexa parasites and yeast, are actively studied from
different perspectives. Inherent to this diversity is a wide range of approaches from classical
genetics to molecular techniques including state-of-the-art nucleic acid analysis, proteomics,
and imaging. Taking advantage of the medical environment, research in microbiology with a
strong translational component is intrinsically linked to immunology and pathology, other
strong research directions at our Faculty.
Prof. Patrick Linder
Vice-President of the Fundamental Medicine Section
HUG – Geneva University Hospitals
FMH – Swiss Medical Association
SNSF – Swiss National Science Foundation
Université de Genève • Faculté de médecine
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The structure of the Faculty favours translational research
Teaching at the Medical Faculty
The Medical Faculty is composed of three different sections: fundamental (SMF), clinical (SMC)
and dental medicine (SMD). Research in microbiology is carried out in all of them as well as in
many different departments. Host-pathogen interactions are thus approached through a
variety of techniques and from very different angles providing an excellent environment for
fundamental, applied and translational research. The mutually beneficial contacts are
supplemented by an array of different platforms that provide expertise and equipment in stateof-the-art techniques (genomic analyses, imaging, proteomics, etc.).
We train medical students in microbiology, immunology and infectious diseases, important
areas in all medical disciplines.
Université de Genève • Faculté de médecine
Aspects of microbiology and immunology appear throughout the teaching modules but are
mainly concentrated in the first and third years of the medical degree. In the third year, an
entire module is devoted to immunity and infection. Within this module, the students learn
the basics about infectious diseases through lectures and problem-oriented teaching before
starting hospital training in the fourth year of their studies. Throughout the Bachelor
programme students are also trained in clinical skills.
Université de Genève • Faculté de médecine
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Host-Pathogen Research at the Faculty
Host-Pathogen Interactions
at the Medical Faculty of the University of Geneva
Fundamental Medicine
• Department of Microbiology and Molecular Medicine
• Department of Pathology and Immunology
• Department of Physiology and Cellular Metabolism
Clinical Medicine
• Department of Internal Medicine Specialties
Division of Infectious Diseases (HUG)
Infection Control Programme (HUG)
• Department of Internal Medicine, Rehabilitation
and Geriatrics
• Department of Pediatrics
• Department of Anaesthesiology, Pharmacology
and Intensive Care (APSI)
• Department of Health and Community Medicine
Division of International and Humanitarian
Medicine (HUG)
Dental Medicine
• Division of Periodontology and Oral Pathophysiology
• Division of Cariology and Endodontics
Bacteriology
Dominique Belin
Department of Pathology and Immunology
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Patrick Linder
Department of Microbiology and Molecular Medicine
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Patrick Viollier
Department of Microbiology and Molecular Medicine
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Daniel Lew
Department of Internal Medicine Specialties
Division of Infectious Diseases (HUG)
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Jacques Schrenzel / Patrice François
Department of Internal Medicine Specialties
Division of Infectious Diseases (HUG)
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William Kelley
Department of Internal Medicine Specialties
Infectious Diseases Service (HUG)
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Christian van Delden
Department of Internal Medicine Specialties,
Department of Microbiology and Molecular Medicine
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Virology
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Université de Genève • Faculté de médecine
Dominique Garcin
Department of Microbiology and Molecular Medicine
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Oliver Hartley
Department of Pathology and Immunology
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Daniel Pinschewer
Department of Pathology and Immunology
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Laurent Roux
Department of Microbiology and Molecular Medicine
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Université de Genève • Faculté de médecine
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Michel Strubin
Department of Microbiology and Molecular Medicine
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Irène Garcia-Gabay
Department of Pathology and Immunology
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Laurent Kaiser / Caroline Tapparel Vu
Department of Internal Medicine Specialties
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Pierre Cosson
Department of Cell Physiology and Metabolism
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Jérôme Pugin
Department of Anaesthesiology, Pharmacology and Intensive Care
Department of Microbiology and Molecular Medicine
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Karl-Heinz Krause
Department of Pathology and Immunology
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Francesco Negro
Department of Internal Medicine Specialties
Department of Pathology and Immunology
Parasitology
Dominique Soldati-Favre
Department of Microbiology and Molecular Medicine
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Vaccinology
François Chappuis
Department of Health and Community Medicine
Division of International and Humanitarian Medicine (HUG)
Médecins sans Frontières
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Claire-Anne Siegrist
Department of Pathology and Immunology
Department of Pediatrics
WHO Collaborative Center for Vaccine Immunology
Louis Loutan
Department of Health and Community Medicine,
Division of International and Humanitarian Medicine (HUG)
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Mycology
Martine Collart
Department of Microbiology and Molecular Medicine
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Dental Bacteriology
Serge Bouillaguet
Division of Cariology and Endodontics
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Andrea Mombelli
Division of Periodontology and Oral Pathophysiology
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Hygiene and Infection control
Host Response
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Alain Gervaix
Department of Pediatrics
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Klara Posfay-Barbe
Department of Pediatrics
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Marc Chanson
Department of Pediatrics
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Université de Genève • Faculté de médecine
Didier Pittet
Infection Control Programme, HUG
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Stephan Harbarth
Infection Control Programme, HUG
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Benedetta Allegranzi
Infection Control Programme, HUG
WHO “Clean Care is Safer Care” Programme
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Université de Genève • Faculté de médecine
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Bacteriology
Bacteriology
Dominique Belin
Department of Pathology and Immunology
Dominique Belin obtained his PhD in 1979 at the University of Geneva. He attended Rockefeller
University in New York for three years as a postdoctoral Fellow, and then became visiting
Associate Professor at Harvard Medical School, Boston (1990-1994). He was appointed Associate
Professor (2002) and then full Professor (2009) of the Department of Pathology and
Immunology.
Genetic analysis of the translocation machinery in E. coli and of unknown genes of
bacteriophages T4
Our studies of the interaction of signal sequences with the translocation machinery in E. coli,
has led to the identification of a new class of mutations that selectively decrease export
mediated by mutant or foreign signal sequences. We have also developed a gain-of-function
bioinformatic and biochemical system to define the parameters of signal sequences.
We are currently investigating the potential functions of phage T4 unknown genes. We have
identified inserts that are toxic when expressed and are concentrating our efforts on gene 55.1.
High expression of 55.1 prevents growth while low expression confers a high sensitivity to UV
irradiation caused by a deficient repair. We have isolated phage and bacterial suppressors of
these phenotypes. This approach will be extended to the other toxic unknown genes of T4.
Mattenberger Y, Mattson S, Métrailler J, Silva F, Belin D (2011) 55.1, a gene of unknown function
of phage T4, impacts on Escherichia coli folate metabolism and blocks DNA repair by the
NER. Mol Microbiol. 82:1406-21
Van Stelten J, Silva F, Belin D & Silhavy T (2009) Effects of Antibiotics and a Proto-Oncogene
Homolog on Destruction of Protein Translocator SecY. Science 325: 753-6.
Biéler S, Silva F, Soto C & Belin D (2006) Bactericidal Activity of both Secreted and Non-secreted
Microcin E492 Requires the Mannose Permease. J. Bact. 188, 7049-61.
Belin D, Guzman LM, Bost S, Konakova M, Silva F & Beckwith J (2004) Functional activity of
eucaryotic signal sequences in Escherichia coli: the ovalbumin family of serine protease
inhibitors. J. Mol. Biol. 335, 437-53.
Guzman LM, Belin D, Carson MJ and Beckwith J (1995) Tight regulation, modulation, and high
level expression by vectors containing the arabinose PBAD promoter. J. Bact. 177, 4121-4130.
Bost S and Belin D (1995). A new genetic selection identifies essential residues in SecG, a
component of the Escherichia coli protein export machinery, The EMBO Journal 14,
4412-4421.
Contact: [email protected]
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Université de Genève • Faculté de médecine
Université de Genève • Faculté de médecine
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Bacteriology
Bacteriology
Patrick Linder
Department of Microbiology and Molecular Medicine
Patrick Linder obtained his undergraduate training in Basel and his PhD on replication in
Escherichia coli at the University of Geneva in 1984. He spent three years in Gif-sur-Yvette in
France as a postdoctoral Fellow, before he came back to Switzerland as Junior Group Leader at
the Biozentrum, University of Basel. He was appointed Lecturer at the University of Geneva in
1994, Associate Professor in 2000 and full Professor in 2007 of the Department of Microbiology
and Molecular Medicine.
RNA metabolism and horizontal gene transfer in Staphylococcus aureus
Our group has a long-standing interest in the biological role of DEAD-box RNA helicase family
proteins. These RNA helicases unwind short RNA duplexes, displace proteins from RNA, or
function as regulated clamps on RNA. They are therefore ideal key players in gene expression.
After studying DEAD-box proteins in yeast for many years, our group switched gradually to the
analysis of RNA helicases in the opportunistic pathogen S. aureus. Our main focus is the analysis
of two RNA helicases and their role in virulence expression and adaptation to different growth
conditions.
One of the helicases is required for efficient biofilm formation in a clinical S. aureus strain.
Recent data indicate that it is part of the degradosome and thereby regulates the abundance
of a central regulatory RNA, the mRNA of the agr quorum sensing system, thus regulating
adhesion versus dispersal.
The second RNA helicase seems to confer increased resistance to acid stress and may influence
survival in neutrophils.
Bacterial DEAD-box RNA helicases, characterised by their
conserved motifs, are involved in ribosome biogenesis, translation
initiation and RNA decay and thereby contribute to the versatility
of these microorganisms.
Redder P & Linder P (2012) New Range of Vectors with a Stringent 5-Fluoroorotic Acid-Based
Counterselection System for Generating Mutants by Allelic Replacement in Staphylococcus
aureus. Appl Environ Microbiol 78:3846-3854.
Linder P and Jankowsky E (2011) From unwinding to clamping - the DEAD box RNA helicase
family. Nat Rev Mol Cell Biol 12, 505-516. [review]
Xu SY, Corvaglia AR, Chan SH, Zheng Y, Linder P (2011) A type IV modification-dependent
restriction enzyme SauUSI from Staphylococcus aureus subsp. aureus USA300. Nucleic Acids
Res. 39, 5597-610
Corvaglia AR, François P, Hernandez D, Perron K, Linder P*, Schrenzel J (2010) A type III-like
restriction endonuclease functions as a major barrier to horizontal gene transfer in clinical
Staphylococcus aureus strains. Proc Natl Acad Sci U S A. 107:11954-8.
* corresponding author; “Editors choice” in Science, selected by the Faculty of 1000 Biology.
Banroques J, Doère M, Dreyfus M, Linder P, Tanner NK (2010) Motif III in the superfamily 2
”helicases” helps convert the binding energy of ATP into a high affinity RNA binding site in
the yeast DEAD-box protein Ded1. J. Mol. Biol. 396:949-96
Contact: [email protected]
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Université de Genève • Faculté de médecine
Université de Genève • Faculté de médecine
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Bacteriology
Bacteriology
Patrick Viollier
Department of Microbiology and Molecular Medicine
Patrick Viollier graduated in 1999 with a PhD in Microbiology from the Biozentrum, University
of Basel. After a four-year postdoctoral course at the Stanford University School of Medicine
he joined the Case Western Reserve University School of Medicine as Assistant Professor in
2004. In 2009 he was appointed Associate Professor in the Department of Microbiology and
Molecular Medicine at the Faculty of Medicine.
Bacterial cell cycle control
We study the molecular mechanisms that coordinate events during the bacterial cell division
and developmental cycle using a powerful genetic and synchronisable model system: the
dimorphic alpha-proteobacterium Caulobacter crescentus. In the past we relied on
comprehensive forward genetic and cell biological approaches to uncover polarity factors that
couple polar differentiation with the cell division cycle in Caulobacter. We also identified an
oxido-reductase-like cytokinetic regulator that coordinates cell division with the differentiation
programme in response to NAD(H) and found that diffusion barrirers can exist within bacterial
subcellular compartment (stalk, green) cells that have a volume in the femtoliter range.
We now also use Caulobacter to explore how bacteriophages (black arrow) seize the cell cycle
machinery, to illuminate how viral-host replication cycles are coordinated at the most
fundamental level.
Hughes HV, Huitema E, Pritchard S, Keiler K, Brun YV and Viollier PH (2010) Protein localization
and dynamics within a bacterial organelle. PNAS 107:5599-604.
Radhakrishnan SK, Pritchard S and Viollier PH (2010) Coupling prokaryotic cell fate cell fate and
division control by a bifunctional and oscillating oxido-reductase homolog.
Dev Cell 18:90-101.
Radhakrishnan SK, Thanbichler M and Viollier PH (2008) The dynamic interplay between a cell
fate determinant and a lysozyme homolog drives the asymmetric division cycle of
Caulobacter crescentus. Genes Dev. 22: 212-25.
Huitema E, Matteson D, Pritchard S, Kumar Radhakrishnan S and Viollier PH (2006) Bacterial
birth scar proteins mark future flagellum assembly site. Cell 124:1025-37.
Holtzendorff J, Hung D, Brende P, Reisenauer A, Viollier PH, McAdams HH and L. Shapiro (2004)
Oscillating Global Regulators Control the Genetic Circuit Driving a Bacterial Cell Cycle.
Science 304(5673):983-7.
Contact: [email protected]
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Université de Genève • Faculté de médecine
Université de Genève • Faculté de médecine
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Bacteriology
Bacteriology
Daniel Lew
Department of Internal Medicine Specialties
Division of Infectious Diseases (HUG)
Daniel Lew obtained his Doctorate of Medicine in 1976 from the University of Geneva. He holds
FMH-certified specialised qualifications in internal medicine and in infectious disease. He was
Clinical and Research Fellow at Harvard Medical School before coming back to Geneva. In 1989
he was appointed full Professor, Head of Infectious Diseases Division, at the Department of
Internal Medicine.
Research activity
Between 1980 and 2003 we studied signal transduction (in particular intracellular calcium)
and activation mechanisms in neutrophils.
As a secondary subject, we established a group interested in the physiopathology of foreign
body infection and osteomyelitis (in particular the pathogenic role of S.aureus).
Since 2003 a new group interested in signaling and glycopeptide resistance in S.aureus has
been formed and participates in the creation of a large thematic area involving several groups
with SNSF funding in S.aureus research in the Infectious Diseases Service.
Translational activities
One of the main aims of the Infectious Diseases Service was to achieve a high level of
integration containing Research Laboratories, Clinical Microbiology Laboratories (Bacteriology
and Virology) and a Clinical Service with consultations in all the services of our hospital as well
as the development of Infection Control (now a fully independent service in the hospital but
integrated into our service at the academic level). This has led to several training programmes
at various levels and clinical research groups with multiple interactions.
Galbusera E*, Renzoni A*, Andrey DO, Monod A, Barras C, Tortora P, Polissi A, and Kelley WL (2011)
Site-specific mutation of Staphylococcus aureus VraS reveals a crucial role for the VraR-VraS
sensor in the emergence of glycopeptide resistance. Submitted Antimicrob Agents
Chemother 55:1008-20
*Both authors contributed equally to this work.
Ferry T, Uçkay I, Vaudaux P, François P, Schrenzel J, Harbarth S, Laurent F, Bernard L, Vandenesch
F, Etienne J, Hoffmeyer P, Lew D (2010) Risk factors for treatment failure in orthopedic devicerelated methicillin-resistant Staphylococcus aureus infection. Eur J Clin Microbiol Infect Dis.
29:171-80.
Vaudaux P, Huggler E, Bernard L, Ferry T, Renzoni A, Lew DP (2010) Underestimation of
vancomycin and teicoplanin MICs by broth microdilution leads to underdetection of
glycopeptide-intermediate isolates of Staphylococcus aureus. Antimicrob Agents Chemother
Sep 54:3861-70.
Renzoni A, Kelley WL, Barras C, Monod A, Huggler E, François P, Schrenzel J, Studer R, Vaudaux
P and Lew DP (2009) Identification by genomic and genetic analysis of two new genes
playing a key role in glycopeptide intermediate resistance in Staphylococcus aureus.
Antimicrob Agents Chemother 53: 903-911.
Renzoni A, Barras C, François P, Charbonnier Y, Huggler E, Garzoni C, Kelley WL, Majcherczyk P,
Schrenzel J, Lew DP and Vaudaux P (2006). Transcriptomic and functional analysis of an
autolytic-deficient teicoplanin-resistant derivative of methicillin-resistant Staphylococcus
aureus. Antimicrobial Agents and Chemotherapy 50: 3048-61.
Contact: [email protected]
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Université de Genève • Faculté de médecine
Université de Genève • Faculté de médecine
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Bacteriology
Bacteriology
Jacques Schrenzel
Department of Internal Medicine Specialties
Division of Infectious Diseases (HUG)
Jacques Schrenzel obtained his medical degree in 1989 at the University of Geneva. After clinical
training at the Geneva University Hospitals (HUG) he carried out research on neutrophils in
infectious diseases. He was postdoctoral Fellow at the Mayo Clinic in Rochester, Minnesota
from 1997 to 2000. On his return to Geneva he was awarded an Assistant Professorship by the
Swiss National Science Foundation and became a pioneer in the genomic analysis of pathogens
(www.genomic.ch). Since 2004 he has been responsible for the Central Bacteriology Laboratory
of the HUG and was appointed Associate Professor in 2010.
Persistence and virulence in Staphylococcus aureus infections
Metagenomics of infectious diseases
We study the pathogenesis of S. aureus infections with a special focus on its ability to persist
as well as to survive host defences. This more specifically concerns the mechanisms of biofilm
formation and the capacity of the bacteria to survive within eukaryotic cells by regulating the
gene expression of numerous bacterial metabolic and virulence-related targets. These
approaches used bacterial genetics, home-brew high-density microarrays and, more recently,
next generation sequencing. This explains the creation of our own bioinformatics group and
the more recent development of research topics using metagenomics to address clinically
relevant questions, within local and international consortia.
Corvaglia AR, François P, Hernandez D, Perron K, Linder P and Schrenzel J (2010) A novel
restriction endonuclease functions as a major barrier to horizontal gene transfer in clinical
Staphylococcus aureus strains. PNAS 107:11954-11958. Editor’s choice, Science 329:121.
Lazarevic V, Whiteson K, Hernandez D, François P, Schrenzel J (2010) Study of inter- and intraindividual variations in the salivary microbiota. BMC Genomics 11:523.
François P, Harbarth S, Huyghe A, Renzi G, Bento M, Gervaix A, Pittet D and Schrenzel J (2008)
Methicillin-Resistant Staphylococcus aureus, Geneva, Switzerland 1993-2005. Emerg Infect
Dis 14:304-307.
Hernandez D, François P, Farinelli L, Osteras M, and Schrenzel J (2008) De novo Bacterial Genome
Sequencing: Millions of Very Short Reads Assembled on a Desktop Computer. Genome
Research 18:802-809.
Garzoni C, François P, Huygue A, Tapparel C, Charbonnier Y, Renzoni A, Couzinet S, Lucchini S,
Lew D, Vaudaux P, Kelly WI and Schrenzel J (2007) A Global View of Staphylococcus aureus
Whole Genome Expression Upon Internalization in Human Epithelial Cells. BMC Genomics
8:171.
Contact: [email protected]
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Université de Genève • Faculté de médecine
Université de Genève • Faculté de médecine
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Bacteriology
Bacteriology
Patrice François / Jacques Schrenzel
(Genomic Research Lab)
Fischer A, Yang SJ, Bayer AS, Vaezzadeh AR, Herzig S, Stenz L, Girard M, Sakoulas G, Scherl A,
Yeaman MR, Proctor RA, Schrenzel J, François P (2011) Daptomycin-Resistance mechanisms
in clinically-derived S. aureus strains assessed by a combined transcriptomics and
proteomics approach. Journal of Antimicrobial Chemotherapy 66:1696-711.
Nair D, Memmi G, Hernandez D, Bard J, Beaume M, Gill S, Francois P, Cheung AL (2011) Whole
genome sequencing of Staphylococcus aureus strain RN4220, a key laboratory strain used
in virulence research, identifies mutations that affect not only virulence factors but also
the fitness of the strain. Journal of Bacteriology 193:2332-5.
Patrice François obtained his PhD degree at the University of Paris XIII in 1996. In 2000 he was
involved in the creation of the Genomic Research Laboratory at Geneva University Hospitals.
His primary research interests are mechanisms of S. aureus adhesion to foreign body and roles
of small RNAs on bacterial pathogenicity. He obtained his Privat Docent in 2011.
Deciphering the virulence of S. aureus infections
Using the capacity of massively parallel methods such as microarrays or high-throughput
sequencing, we aim to explore all genomic elements potentially involved in epidemiological
or virulence traits of MRSA. We study at the genome scale those genetic events that potentially
trigger bacterial adaptation as evidenced by modifications in spreading, virulence and
pathogenicity. Our main efforts involve genomic regions that remain poorly explored to date,
namely the segments considered so far as intergenic regions, in order to unravel genomic
elements responsible for “the success of S. aureus” in clinical or epidemiological settings. We
are now characterising small RNA molecules that we have discovered in S. aureus for their
potential roles as regulatory RNA during infection.
This work is under the direct supervision of Patrice François as part of the research structure
established by J. Schrenzel.
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Université de Genève • Faculté de médecine
Beaume MD, Hernandez L, Farinelli M, Osteras J, Schrenzel J, François P (2010) Cartography of
Methicillin-Resistant Staphylococcus aureus Transcripts: Detection, Orientation and
Temporal Expression during Growth Phase and Stress Conditions. Plos One 20;5:e10725.
Megevand C, Gervaix A, Heininger U, Berger C, Aebi C, Vaudaux B, Kind C, Gnehm HP, Hitzler
M, Renzi G, Schrenzel J, François P (2010) Molecular epidemiology of the nasal colonization
by methicillin-susceptible Staphylococcus aureus in Swiss children. Clin.Microbiol.Infect.
16:1414-1420.52.
François P, Scherl A, Hochstrasser D and Schrenzel J (2010) Proteomic approaches to study
Staphylococcus aureus pathogenesis. J. Proteomics 73:701-708.
Lazarevic V, Whiteson K, Huse S, Hernandez D, Farinelli L, Osteras M, Schrenzel J and François P
(2009) Metagenomic study of the oral microbiota by Illumina high-throughput sequencing.
J.Microbiol.Methods 79:266-271.
François P, Uckay I, Iten A, Renzi G, Dahran S, Camus V, Sax H and Schrenzel J (2008) In vivo
detection of clonally derived methicillin-resistant/methicillin-susceptible Staphylococcus
aureus strains is not a rare event. J.Clin.Microbiol. 46:1890-1891.
Contact: [email protected]
Université de Genève • Faculté de médecine
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Bacteriology
Jacques Schrenzel
(Clinical Bacteriology Lab)
Clinically relevant and efficient microbiological diagnosis
The bacteriology lab is a production-oriented laboratory that aims to provide rapid and clinically
relevant bacterial diagnosis for patients at the Geneva University Hospitals (HUG). We host the
National Reference Center for Meningococci. Efforts are concentrated on reducing turn-around
times by implementing state-of-the art methods such as MALDI-TOF, PCR-ESI-MS or other
molecular methods before they are commercially available. We also have a track record of assay
development in the research lab followed by successful technology transfer to the routine lab,
mostly for infection control purposes (detection and genotyping of MRSA, Clostridium difficile,
ESBL, etc.). We always pay particular attention to building upon local competences (infection
control service, etc.) and expanding them by creating international consortia whenever needed.
Bacteriology
Afshari A, Schrenzel J, Ieven M, Harbarth S (2012) Bench-to-bedside review: Rapid molecular
diagnostics for bloodstream infection - a new frontier? Crit Care 29 :16-222
Poirel L, Schrenzel J, Cherkaoui A, Bernabeu S, Renzi G, Nordmann P (2011) Molecular analysis
of NDM-1-producing enterobacterial isolates from Geneva, Switzerland. J Antimicrob
Chemother 66:1730-3.
Kaleta EJ, Clark AE, Cherkaoui A, Wysocki VH, Ingram EL, Schrenzel J, Wolk DM (2011)
Comparative Analysis of PCR-Electrospray Ionization/Mass Spectrometry (MS) and MALDITOF/MS for the Identification of Bacteria and Yeast from Positive Blood Culture Bottles. Clin
Chem. 57:1057-67.
Focke M, Stumpf F, Faltin B, Reith P, Bamarni D, Wadle S, Mueller C, Reinecke H, Schrenzel J,
François P, Mark D, Roth G, Zengerle R and Von Stetten F (2010) Microstructuring of polymer
films for highly sensitive genotyping by real-time PCR on a centrifugal microfluidic platform.
Lab-on-Chip 10:2519-2526.
Cherkaoui A, Emonet S, Hibbs J, Tangomo M, Girard M, François P, and Schrenzel J (2010)
Comparison of two Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass
Spectrometry Methods with Conventional Phenotypic Identification for Routine Bacterial
Speciation. J Clin Microb 48:1169-1175.
Ceroni D, Cherkaoui A, Ferey S, Kaelin A and J. Schrenzel (2010) Kingella kingae osteoarticular
infections in young children: clinical features and contribution of a new specific real-time
PCR assay to the diagnosis. J Pediatr Orthop 30:301-304.
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Université de Genève • Faculté de médecine
Université de Genève • Faculté de médecine
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Bacteriology
Bacteriology
William L. Kelley
Department of Internal Medical Specialties
Division of Infectious Diseases (HUG)
William L. Kelley graduated in 1981 from Williams College (USA), with a BA in Biology. In 1991
he obtained a PhD in microbiology-immunology with supplemental specialisation from the
University Programme in Genetics, Duke University Medical Center. Following postdoctoral
studies with molecular chaperones and protein folding, he focused his reseach on
Staphylococci. In 2007 he became Privat-Docent of the HUG in the Department of Internal
Medicine, Infectious Diseases Service.
Staphylococcus aureus environmental sensing systems
Our laboratory studies the range of mechanisms Staphylococcus aureus possesses that link
extracellular signals to changes in gene expression. We are particularly interested in the family
of histidine kinase two-component systems which are widely found in the microbial world.
Our work focuses on two of these systems: VraRS, which responds to cell wall active antibiotics
such as penicillins and glycopeptides, and SrrAB, which responds to aerobic/anaerobic shift
and orchestrates adaptations in energy production and redox balance. Curiously, SrrAB is also
intimately involved in the transcriptional regulation of toxins, such as toxic shock superantigen,
as well as S. aureus’ defence against nitrogen monoxide (NO), a key effector of the innate
immune response. We recently discovered that Spx, a global regulator of thiol and oxidative
stress defence, is essential in S. aureus. Using deep sequencing and genetic methods we have
uncovered novel genes that are Spx-regulated and suggest an important link between sensory
pathways governing redox homeostasis and the general stress response. Collectively, our work
delves into drug resistance mechanisms including MRSA, virulence factor regulation, secretion,
transmembrane signalling, and the discovery of essential genes or processes that constitute
promising targets for therapeutic intervention.
Jousselin A, Renzoni A, Andrey DO, Monod A, Lew DP and Kelley WL (2012) The
posttranslocational chaperone lipoprotein PrsA is involved in both glycopeptide and
oxacillin resistance in Stpahlyococcus aureus. Antimicrobial Agents Chemother. 56: In press.
Renzoni A, Andrey DO, Jousselin A, Barras C, Monod A, Vaudaux P, Lew D and Kelley WL (2011)
Whole genome sequencing and complete genetic analysis reveal novel pathways to
glycopeptides resistance in Staphylococcus aureus. PloS One e21577.
Galbusera E, Renzoni A, Andrey DO, Monod A, Barras C, Tortora P, Polissi A and Kelley WL (2011)
Site-specific mutation of Staphylococcus aureus VraS reveals a crucial role for the VraR-VraS
sensor in the emergence of glycopeptides resistance. Antimicrobial Agents Chemother
55:1008-1020.
Andrey DO, Renzoni A, Monod A, Lew DP, Cheung, AL and Kelley WL (2010) Control of the
Staphylococcus aureus toxic shock tst promoter by the global regulator SarA. J. Bacteriol.
192:6077-6085.
Garzoni C and Kelley WL (2009) Staphylococcus aureus: new evidence for intracellular
persistence. Trends Microbiol. 17:59-65.
Contact: [email protected]
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Université de Genève • Faculté de médecine
Université de Genève • Faculté de médecine
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Bacteriology
Bacteriology
Christian van Delden
Department of Internal Medical Specialties
Department of Microbiology and Molecular Medicine
Christian van Delden obtained his Medical Degree in 1988 at the University of Geneva, then
FMH-certified qualifications in Internal Medicine in 1995 and in Infectious Diseases in 1999.
He held a three-year Postdoctoral Research Fellowship at the University of Rochester, New York
working on virulence regulation in Pseudomonas aeruginosa and returned to Geneva with a
Score A grant from the SNSF. Since 1998 he has led a research laboratory in the Department of
Microbiology and Molecular Medicine, and has been Head of the Immunocompromised Host
Programme at HUG since 2003. He is a co-founder and member of the Executive Office of the
Swiss Transplant Cohort Study and President of the Swiss Transplant Infectious Diseases
Working Group. He was appointed Associate Professor in 2011.
Role of Quorum-Sensing and Socio-Microbiological Behavior in the Pathogenesis of
Pseudomonas aeruginosa infections
Since 1998 we have studied resistance and virulence in P. aeruginosa. Our approach is
translational; we bring clinical hypothesis and strains into the laboratory, use genetics and
molecular microbiology for both “in patient” and “in vitro” studies, and try to implement our
findings at the bedside. With this approach we have characterised the development of
resistance on therapy and have identified novel virulence regulators. Recently we identified
Quorum-Sensing (QS) as a major risk factor for the progression from colonisation to infection
in intubated patients. We also investigated this progression from a socio-microbiological angle
with the development of QS-cheating and microbiological intra-species warfare based on
pyocin production. We further studied the efficacy of inhibiting QS to prevent infection in these
patients. Our clinical research activity involves infections in transplant recipients and their
prevention.
van Delden C, Köhler T, Brunner-Ferber F, Francois B, Carlet J and Pechère JC
(2012) Azithromycin to prevent Pseudomonas aeruginosa ventilator-associated-pneumonia
by inhibition of quorum-sensing: a randomized controlled trial. Intensive Care Med 38:11181125.
Köhler T, Guanella R, Carlet J and van Delden C (2010) Quorum-sensing-dependent virulence
during Pseudomonas aeruginosa colonisation and pneumonia in mechanically ventilated
patients. Thorax 65:703-710.
Köhler T, Perron GG, Buckling A and van Delden C (2010) Quorum sensing inhibition selects for
virulence and cooperation in Pseudomonas aeruginosa PLos Pathogen 6;6:e1000883
Köhler T, Donner V and van Delden C (2010) Lipopolysaccharide as shield and receptor for Rpyocin mediated killing in Pseudomonas aeruginosa. Journal of Bacteriology 192:1921-1928.
Köhler T, Buckling A and van Delden C (2009) Cooperation and virulence of clinical
Pseudomonas aeruginosa populations. Proc Natl Acad Sci USA 106:6339-6344
Contact: [email protected]
26
Université de Genève • Faculté de médecine
Université de Genève • Faculté de médecine
27
Virology
Virology
Dominique Garcin
Department of Microbiology and Molecular Medicine
Dominique Garcin obtained his PhD at the Ecole Normale Supérieure in Lyon in 1989. Thereafter
he joined the Department of Microbiology and Genetics, HUG where he was appointed Lecturer
(Maître d’Enseignement et de Recherche) in 2010.
The molecular basis of ligand recognition by RIG-I and viral escape strategies
Viral infections are responsible for extensive human and animal suffering and death. Very few
antiviral molecules are available and, more importantly, escape mutants resistant to existing
antiviral agents generally emerge rapidly for RNA viruses, due to their high mutation rate. On
the other hand, one of the first lines of defence against viral infection is innate immunity.
Detailed knowledge of how this is established and how viruses escape these antiviral defenses,
is critical for understanding how to prevent viral infection. Our laboratory has long experience
in studying negative strand virus (NSV) RNA synthesis, replication and their interactions with
their host, in particular the IFN antagonists that the virus expresses to counteract the innate
immune response.
Marq JB, Hausmann S, Veillard N, Kolakofsky D, Garcin D (2011) Short double-stranded RNAs
with an overhanging 5’ ppp-nucleotide, as found in arenavirus genomes, act as RIG-I decoys.
J Biol Chem. 286:6108-16
Marq JB, Kolakofsky D and Garcin D (2010) Unpaired 5’ ppp-nucleotides, as found in arenavirus
dsRNA panhandles, are not recognized by RIG-I. J. Biol. Chem. 285: 18208-16.
Marq JB, Hausmann S, Luban J, Kolakofsky D and Garcin D (2009) The dsRNA binding domain
of the vaccinia virus E3L protein inhibits both RNA and DNA-induced activation of , IFNβ.
J.Biol. Chem. 284:25471-8
Hausmann S., Marq JB, TapparelC, Kolakofsky D, Garcin D (2008) RIG-I and dsRNA-Induced IFNβ
Activation. PLoS ONE 3: e3965
Strahle L, Marq JB, Brini A, Hausmann S, Kolakofsky D, Garcin D (2007) Activation of the beta
interferon promoter by unnatural Sendai virus infection requires RIG-I and is inhibited by
viral C proteins. J. Virol. 81: 12227-37
Marq JB, Brini A, Kolakofsky D, Garcin D (2007) Targeting of the Sendai virus C protein to the
plasma membrane via a peptide-only membrane anchor. J. Virol. 81:3187-97
Contact: [email protected]
28
Université de Genève • Faculté de médecine
Université de Genève • Faculté de médecine
29
Virology
Virology
Oliver Hartley
Department of Pathology and Immunology
Oliver Hartley completed his PhD in protein engineering at the University of Cambridge, UK in
1997. Following a brief Fellowship at the Glaxo Institute for Molecular Biology in Geneva, he
joined Robin Offord’s lab as a postdoctoral Fellow at the University of Geneva. He became a
group leader in the Department of Structural Biology and Bioinformatics in 2005, where he
has been an Assistant Professor since 2008.
Macromolecular engineering to prevent infectious diseases
With a focus on the prevention of infectious diseases, our work is based on the engineering of
proteins and peptides to identify new macromolecules with potential use as medicines. Our
main work has involved the engineering of chemokines to produce highly potent HIV entry
inhibitors for use as medicines in prevention. A first clinical study of our best molecule is
scheduled to take place at the HUG in 2012. In addition to continuing fundamental studies of
the unusual inhibitory mechanisms of these molecules, we have recently begun work on the
development of a macromolecular vaccine delivery platform. Our approach, which enables
‘plug-and-play’ incorporation of antigens and immune modulators into multivalent
nanoparticles, is being evaluated in collaboration with colleagues in the Faculty.
Gaertner HF, Cerini F, Kamath A, Rochat A-F, Siegrist C-A, Menin L & Hartley O (2011) Efficient
orthogonal bioconjugation of dendrimers for synthesis of bioactive nanoparticles.
Bioconjugate chemistry 20: 1103-1114.
Escola JM, Kuenzi G, Gaertner H, Foti M, & Hartley O (2010) CC chemokine receptor 5 (CCR5)
desensitization: cycling receptors accumulate in the trans-Golgi network J Biol Chem
285:41772-80
Gaertner H, Cerini F, Escola JM, Kuenzi G, Melotti A, Offord R, Rossitto-Borlat I, Nedellec R,
Salkowitz J, Gorochov G, Mosier D, & Hartley O (2008) Highly potent, fully recombinant
anti-HIV chemokines: reengineering a low-cost microbicide Proc Natl Acad Sci USA
105:17706-17711
Hartley O, Gaertner H, Wilken J, Thompson D, Fish R, Ramos A, Pastore C, Dufour B, Cerini F,
Melotti A, Heveker N, Picard L, Alizon M, Mosier D, Kent S & Offord R (2004) Medicinal
chemistry applied to a synthetic protein: development of highly potent HIV entry inhibitors
Proc Natl Acad Sci USA 101:16460-16465
Lederman MM, Veazey RS, Offord R, Mosier DE, Dufour J, Mefford M, Piatak M Jr, Lifson JD,
Salkowitz JR, Rodriguez B, Blauvelt A & Hartley O (2004) Prevention of vaginal SHIV
transmission in rhesus macaques through inhibition of CCR5 Science 306: 485-487
Contact: [email protected]
30
Université de Genève • Faculté de médecine
Université de Genève • Faculté de médecine
31
Virology
Virology
Daniel Pinschewer
Department of Pathology and Immunology
Daniel Pinschewer obtained his medical Doctorate in 2001. He was awarded a stipendiary
Professorship by the SNSF in 2007 and was appointed full Professor in 2011.
Virus-host balance, pathogenesis and vaccination against persistent infection
Our laboratory has a general interest in antiviral immunity and viral pathogenesis, with three
main foci: i) immune control of persistent viral infections, ii) viral pathogenesis of
”autoimmune” diseases, and iii) virally vectored vaccines against persistent infection. We
approach these topics by exploiting a reverse genetics system for lymphocytic choriomeningitis
virus we have developed. This molecular virological approach is combined with animal models
to investigate virus-host interaction in the systemic organismic context. Our mainly basic rather
than applied research nevertheless aims at addressing questions of medical relevance.
Bonilla WV, Fröhlich A, Senn K, Kallert S, Fernandez M, Johnson S, Kreutzfeldt M, Hegazy AN,
Schrick C, Fallon PG, Klemenz R, Nakae S, Adler H, Merkler D, Löhning M, Pinschewer DD
(2012) The alarmin interleukin-33 drives protective antiviral CD8⁺ T cell responses. Science
335:984-9.
Bergthaler A, Flatz L, Hegazy AN, Johnson S, Horvath E, Löhning M and DD Pinschewer (2010)
Viral replicative capacity is the primary determinant of lymphocytic choriomeningitis virus
persistence and immunosuppression. Proc Natl Acad Sci USA 107:21641-6.
Flatz L, Hegazy AN, Bergthaler A, Verschoor A, Claus C, Fernandez M, Gattinoni L, Johnson S,
Kreppel F, Kochanek S, van den Broek M, Radbruch A, Lévy F, Lambert PH, Siegrist CA, Restifo
NP, Löhning M, Ochsenbein AF, Nabel GJ and DD Pinschewer (2010) Development of
replication-defective lymphocytic choriomeningitis virus vectors for induction of potent
CD8+ T cell immunity. Nat. Med. 16:339-45
Flatz L., Rieger T., Merkler D., Bergthaler A., Regen T., Schedensack M., Bestmann L., Verschoor A.,
Kreutzfeldt M., Brück W., Hanisch U.K., Günther S. and DD Pinschewer (2010). T celldependence of Lassa fever pathogenesis. PLoS Pathog. 26;6(3):e1000836
Bergthaler A, Flatz L, Verschoor A, Hegazy AN, Holdener M, Fink K, Eschli B, Merkler D,
SommersteinR, HorvathE, FernandezM, FitscheA, SennBM, VerbeekJS, OdermattB, Siegrist
CA and DD Pinschewer (2009) Impaired antibody response causes persistence of prototypic
T cell-contained virus. PLoS Biol 7:e1000080
Contact: [email protected]
32
Université de Genève • Faculté de médecine
Université de Genève • Faculté de médecine
33
Virology
Virology
Laurent Roux
Department of Microbiology and Molecular Medicine
Laurent Roux obtained his PhD in 1976 at the Molecular Biology Department of Geneva
University. After three years as a postdoctoral Fellow in the Biology Department at the
University of California San Diego, he became Research Assistant at the Department of Internal
Medicine. He was then appointed as Research Associate in the Department of Genetics and
Microbiology, where he was appointed Associate Professor in 2000 and full Professor in 2009.
Paramyxovirus multiplication cycle: virion morphogenesis and production
Using Sendai virus as a prototype for members of the Paramyxoviridae family, we aim to define:
i) which viral constituent(s) is (are) required for formation of virus particles, and ii) which
mechanisms prevail in the incorporation of the viral constituents into the virus particles. We
have developed an integrated suppression complementation (ISCS) system that allows a
structure-function analysis of the viral proteins in the context of an infection. The aim of this
study is twofold: i) acquisition of fundamental information about the mechanisms that prevail
in the formation of Paramyxovirus virus particles, and ii) the ability to produce virus particles
that express on their envelope defined surface antigens and that could serve as vaccine vectors.
Miazza V, Mottet-Osman G, Startchick S, Chaponnier C and Roux L (2011) Sendai virus induced
cytoplasmic actin remodeling correlates with efficient virus particle production. Virology,
410:7-16.
Gosselin-Grenet AS, Mottet-Osman G, Roux L (2010). Sendai virus particle production: Basic
requirements and role of the SYWST motif present in HN cytoplasmic tail. Virology, 405:
439-447.
Gosselin-Grenet AS, Marq, JB, Garcin D and Roux L (2007). Sendai virus budding in the course
of an infection does not require Alix and VPS4A host factors. Virology 365: 101-112.
Mottet-Osman G, Iséni F, Pelet T, Wiznerowicz M, Garcin D and Roux L (2007). Suppression of
the Sendai virus M protein through a novel siRNA approach inhibits viral particle production
but does not affect viral RNA synthesis. J. Virol. 81: 2861-2868.
Gosselin-Grenet AS, Mottet-Osman G and Roux L (2006). From assembly to virus particle
budding: pertinence of the detergent resistant membranes. Virology 344: 296-303
Contact: [email protected]
34
Université de Genève • Faculté de médecine
Université de Genève • Faculté de médecine
35
Virology
Virology
Michel Strubin
Department of Microbiology and Molecular Medicine
Michel Strubin received his PhD from the University of Geneva in 1987. After initial post-doctoral
training at the ISREC in Lausanne, he left for a two-year stay at Harvard Medical School in
Boston, USA. In 1992 he joined the Department of Microbiology and Molecular Medicine with
a START Fellowship from the SNSF. In 2001 he was appointed Associate Professor in the same
Department.
The HBx protein of Hepatitis B Virus and Regulation of Gene Expression
The HBx protein of hepatitis B virus
Chronic infection by hepatitis B virus (HBV) is a leading cause of liver cancer. HBV encodes a
small protein, known as HBx, which is essential for viral infection and has been implicated in
HBV-associated liver cancer. We found that HBx promotes HBV gene expression by an unusual
mechanism that affects only extrachromosomal DNA templates and that requires HBx to
function as a substrate receptor for a cellular E3 ubiquitin ligase. We now wish to identify the
substrate(s) recruited by HBx to the E3 ligase and further explore the mechanisms whereby
HBx promotes viral gene expression under experimental conditions closer to natural HBV
infection. Because of its uncommon property and key role in viral transcription, HBx may
represent an attractive target for new antiviral therapies.
Regulation of gene expression
We are using yeast as a model system to address fundamental questions about the
mechanisms by which gene transcription is regulated. We are particularly interested in
understanding how the transcription machinery, a large complex that contains many proteins
in addition to the RNA polymerase, assembles at the beginning of genes and how cells control
this event. We also study the dynamics and epigenetic modifications of chromatin and their
importance in transcriptional regulation.
36
Université de Genève • Faculté de médecine
Van Breugel PC, Robert EI, Mueller H, Decorsière A, Zoulim F, Hantz O and Strubin M (2012)
Hepatitis B virus X protein stimulates gene expression selectively from extrachromosomal
DNA templates. Hepatology doi: 10.1002/hep.25928. [Epub ahead of print]
Li, T, Robert EI, van Breugel PC, Strubin M* and Zheng N* (2010) A promiscuous alpha-helical
motif anchors viral hijackers and substrate receptors to the CUL4-DDB1 ubiquitin ligase
machinery. Nat. Struct. Mol. Biol. 17: 105-11
(* corresponding authors)
Jamai A, Puglisi A and Strubin M (2009) Histone chaperone Spt16 promotes redeposition of
the original H3-H4 histones evicted by elongating RNA polymerase. Mol. Cell 35: 377-83
Martin-Lluesma S, Schaeffer C, Robert EI, van Breugel PC, Leupin O, Hantz O and Strubin M
(2008) Hepatitis B virus X protein affects S phase progression leading to chromosome
segregation defects by binding to damaged DNA binding protein 1. Hepatology 48: 146776.
Jamai A, Imoberdorf, RM and Strubin, M (2007) Continuous histone H2B and transcriptiondependent histone H3 exchange in yeast cells outside of replication. Mol. Cell 25, 345-55.
Contact: [email protected]
Université de Genève • Faculté de médecine
37
Virology
Virology
Laurent Kaiser
Department of Internal Medicine Specialties
Laurent Kaiser obtained his Medical Degree in Geneva in 1987 and a medical
thesis in 1996. He completed a full training in Internal Medicine and a board
certification in Infectious Diseases in 1999 and in clinical microbiology in
2006. He spent two years as a research associate at the University of Virginia
in Charlottesville, USA. He has been appointed associate professor at the
Faculty of Medicine in 2006 and is Director of the Laboratory of Virology at the Geneva
University Hospitals.
Clinical virology
Based within the HUG, the laboratory performs more than 140,000 diagnostic procedures
annually. It runs a complete panel of virological tests adapted to a large university centre caring
for immunocompromised patients and transplant recipients, including serology, antigen
detection, automated and non-automated molecular assays, viral sequencing and virus culture.
The goal of the team is to integrate the activities of a routine laboratory with clinical
developments, new diagnostic assays, and basic research in the field of virology.
Reference centers: influenza and emerging viral diseases
The laboratory integrates and supports two National Reference Centres funded by the Swiss
Federal Office of Public Health. This team conducts influenza surveillance in Switzerland and
provides basic diagnostic capabilities for unusual and rare viral diseases. This includes
potentially dangerous agents as well as more common viruses that are not part of routine
diagnostic procedures in most laboratories.
Clinical research: respiratory viruses
The clinical research conducted by the group aims to investigate the clinical impact and
epidemiology of respiratory viruses by using appropriate molecular assays. In particular,
investigations have focused on the impact of respiratory viruses in immunocompromised hosts
and European or African children. Close collaboration with the basic research group allows the
investigation of unusual clinical observations in the field of clinical virology and promotes
translational projects.
Acute HIV infection and resistance
Cordey S, Petty TJ, Schibler M, Martinez Y, Gerlach D, Van Belle S, Turin L, Zdobnov E, Kaiser L,
Tapparel C (2012) identification of site-specific adaptations conferring increased neural cell
tropism during human enterovirus 71 infection. PloS Pathogens. [Epub ahead of print]
Tapparel C, Cordey S, Junier Th, Farinelli L, Van Belle S, Soccal PM, Aubert JD, Zdobnov E, Kaiser
L (2011). Rhinovirus Genome Variation during Chronic Upper and Lower Respiratory Tract
Infections. PLoS ONE 6: e21163.
Soccal PM, Aubert JD, Bridevaux PO, Garbino J, Thomas Y, Rochat T, Rochat TS, Meylan P, Tapparel
C, Kaiser L (2010) Upper and lower respiratory viral infections and acute graft rejection in
lung transplant recipients. Clin Infect Dis 51: 163-170.
Cordey S, Junier T, Gerlach D, Gobbini F, Farinelli L, Zdobnov E, Winther B, Tapparel C, Kaiser L
(2010) Rhinovirus Genome Evolution during Experimental Human Infection. PloS One
5 :e10588- e10588.
Yerly S, Junier T, Gayet-Ageron A, Amari EB, von Wyl V, Günthard HV, Hirschel B, Zdobnov E, Kaiser
L (2009) The impact of transmission clusters on primary drug resistance in newly diagnosed
HIV-1 infection. Swiss HIV Cohort Study, AIDS 23 : 1415-23.
Tapparel C, Junier T, Gerlach D, Van Belle S, Turin L, Cordey S, Mühlemann K, Regamey N, Aubert
JD, Soccal PM, Eigenmann P, Zdobnov E and Kaiser L (2009) New respiratory enterovirus and
recombinant rhinoviruses among circulating picornaviruses. Emerg Infect Dis. 15: 719-26.
Garbino J, Soccal PM, Aubert JD, Rochat T, Meylan P, Thomas Y, Tapparel C, Bridevaux PO, Kaiser
L (2009) Respiratory viruses in bronchoalveolar lavage: a hospital-based cohort study in
adults. Thorax, vol 64: 399-404.
Contact: [email protected]
This group (Sabine Yerly) has built recognised expertise in the field of HIV diagnostics, acute
HIV infection and molecular epidemiology of HIV transmission. The group acts also as a
reference centre for the study of HIV resistance-associated mutations and the interpretation
of new resistance patterns. This activity has the advantage of being immediately beneficial to
the clinician in charge of managing complex antiretroviral regimens.
38
Université de Genève • Faculté de médecine
Université de Genève • Faculté de médecine
39
Virology
Virology
Caroline Tapparel Vu
Department of Internal Medicine Specialties
Caroline Tapparel Vu obtained her PhD in Molecular Virology in 1998 at the Faculty of Medicine
in Geneva. After postdoctoral training in human genetics and bacteriology, she set up basic
research on rhinoviruses and enteroviruses in the Department of Internal Medicine in 2005.
Insights into rhino/enterovirus diversity and evolution
Rhinoviruses and enteroviruses are small non-enveloped positive strand RNA viruses within
the Enterovirus genus of the Picornaviridae family. Human rhinoviruses (HRV) are frequently
associated with upper respiratory tract diseases and exacerbations of pre-existing disorders
such as asthma. Human enteroviruses (HEV) contain important neurotropic pathogens such
as Poliovirus or Enterovirus 71 (EV71). HRV and HEV are characterised by high genetic variability
which complicates the development of antivirals or vaccines. Our research group aims to
improve the understanding of the large phenotypic diversity observed among these closely
related viruses. Thanks to reverse genetic assays the group investigates the correlation between
genomic features and specific viral phenotypes.
In addition, two of the major mechanisms of picornavirus evolution, recombination and
mutations, are studied in vitro and during natural human infections, with the help of nextgeneration sequencing approaches. Furthermore, we continue to develop novel generic
molecular tools to detect and quantify divergent viral strains with greater sensitivity.
Cordey S, Petty TJ, Schibler M, Martinez Y, Gerlach D, Van Belle S, Turin L, Zdobnov E, Kaiser L,
Tapparel C (2012) Identification of site-specific adaptations conferring increased neural cell
tropism during human enterovirus 71 infection. PloS Pathogens Epub ahead of print
Schibler M, Yerly S, Vieille G, Docquier M, Turin L, Kaiser L, Tapparel C (2012) A Critical Analysis
of Rhinovirus RNA Load Quantification by Real-TIme RT-PCR. J Clin Microbiol Epub ahead
of print.
Schibler M, Gerlach D, Martinez Y, Van Belle S, Turin L, Kaiser L, Tapparel C (2011) Experimental
Human Rhinovirus and Enterovirus Interspecies Recombination. J Gen Virol 93: 93-101.
Tapparel C, Cordey S, Junier T, Farinelli L, Van Belle S, Soccal PM, Aubert JD, Zdobnov E, Kaiser L
(2011) Rhinovirus Genome Variation during Chronic Upper and Lower Respiratory Tract
Infections. PLoS One 6:e21163.
Cordey S, Junier T, Gerlach D, Gobbini F, Farinelli L, Zdobnov E, Winther B, Tapparel C, Kaiser L
(2010) Rhinovirus genome evolution during experimental human infection PLoS One
5:e10588.
Tapparel C, Cordey S, Van Belle S, Turin L, Lee WM, Regamey N, Meylan P, Mühlemann K, Gobbini
F, Kaiser L (2009) New molecular detection tools adapted to emerging rhinoviruses and
enteroviruses. J Clin Microbiol 47:1742-9
Tapparel C, Junier T, Gerlach D, Van Belle S, Turin L, Cordey S, Mühlemann K, Regamey N, Aubert
JD, Soccal PM, Eigenmann P, Zdobnov E, Kaiser L (2009) New respiratory enterovirus and
recombinant rhinoviruses among circulating picornaviruses. Emerg Infect Dis 15:719-26.
Contact: [email protected]
40
Université de Genève • Faculté de médecine
Université de Genève • Faculté de médecine
41
Virology
Virology
Francesco Negro
Department of Internal Medicine
Department of Pathology and Immunology
Francesco Negro obtained his Medical Degree in 1982 at the University of Turin, Italy. He was
postdoctoral Fellow in Georgetown, University School of Medicine, Rockville, Maryland, USA
from 1986 to 1989, and guest researcher at the Laboratory of Infectious Diseases at the National
Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA in 1989. After having
spent some time back in Turin, he joined the HUG in 1994. He was appointed Associate
Professor in 2006.
Pathogenesis of chronic hepatitis C
Our laboratory studies the pathogenesis of chronic hepatitis C, including both hepatic and
extrahepatic manifestations, with particular regard to: HCV-induced fatty liver; HCV-induced
insulin resistance; interactions between HCV and the metabolic syndrome;
factors/mechanisms of liver disease progression and resistance to interferon alpha-based
antiviral therapy (particularly host genetic and metabolic factors). This research is carried out
through the following approaches: in vitro, using (i) different expression models of single HCV
proteins (including lentivectors), (ii) subgenomic-length or full-length (infectious) HCV replicon
systems, and (iii) co-cultures of HCV-expressing hepatoma cells with other cell types of major
relevance in the pathogenesis of the metabolic syndrome as well as in vivo, using human
tissues (liver and peripheral blood mononuclear cells), taken in the setting of various
observational and interventional clinical trials
Bochud PY, Bibert S, Kutalik Z, Patin E, Guergnon J, Nalpas B, Goossens N, Kuske L, Müllhaupt B,
Gerlach T, Heim M, Moradpour D, Cerny A, Malinverni R, Regenass S, Dollenmaier G, Hirsch
H, Martinetti G, Gorgiewski M, Bourlière M, Poynard T, Theodorou I, Abel L, Pol S, Dufour JF,
Negro F (2012) IL28B alleles associated with poor HCV clearance are protective against liver
necroinflammatory activity and fibrosis progression in patients infected with non-1 HCV
genotypes. Hepatology 55:384-394
Clément S, Peyrou M, Sanchez-Pareja A, Bourgoin L, Ramadori P, Suter DM, Vinciguerra M,
Guilloux K, Pascarella S, Rubbia-Brandt L, Negro F, Foti M (2011) Downregulation of PTEN
and IRS1 by HCV 3a core protein triggers steatosis in hepatocytes. Hepatology 54:38-49
Bochud PY, Cai T, Overbeck K, Bochud M, Rickenbach M, Dufour JF, Muellhaupt B, Borovicka J,
Heim M, Moradpour D, Cerny A, Malinverni R, Francioli P, Negro F (2009) Genotype 3 is
associated with accelerated fibrosis progression in chronic hepatitis C. J Hepatol 51:655-666
Clement S, Juge-Aubry C, Conzelmann S, Pazienza V, Pittet-Cuenod B, Meier C, Negro F (2008)
Monocyte chemoattractant protein-1 secreted by adipose tissue induce lipid accumulation
in hepatocytes. Hepatology 48:799-807
Leandro G, Mangia A, Hui J, Fabris P, Rubbia-Brandt L, Colloredo G, Adinolfi LE, Asselah T, Jonsson
JR, Smedile A, Terrault N, Pazienza V, De Lalla F, Giostra E, Sonzogni A, Ruggiero G, Marcellin
P, Powell EE, George J, Negro F (2006) The relationship between hepatic steatosis,
inflammation and fibrosis in chronic hepatitis C: a meta-analysis of individual patient data.
Gastroenterology 130: 1636-1642
Contact: [email protected]
42
Université de Genève • Faculté de médecine
Université de Genève • Faculté de médecine
43
Parasitology
Parasitology
Dominique Soldati-Favre
Department of Microbiology and Molecular Medicine
Active host cell entry
Intracellular replication
Dominique Soldati-Favre obtained her PhD degree at the University of Zürich in 1990. She was
then a postdoctoral Fellow at Stanford University, Assistant Professor at the University of
Heidelberg and Reader at Imperial College London. She was appointed Associate Professor in
2004 at the Department of Microbiology and Molecular Medicine and then full Professor in
2010. Dominique Soldati-Favre has been Vice-Dean of the Faculty since 2011.
Study of factors governing invasion and replication in Apicomplexan parasites
Gliding motility is a unique attribute of the phylum Apicomplexa, which is crucial for parasite
migration across biological barriers, host cell invasion and egress from infected cells. Timing
and orientation of gliding motility are tightly regulated by formins that spatially control actin
filaments polymerisation by assembly of a functional motor complex, which is governed by
posttranslational modifications and by the action of a rhomboid protease, which disengages
parasite adhesins and host receptors complexes and trigger the switch from an invasive to a
replicative mode. Our research focuses on regulators of actin dynamics, myosin motors,
adhesins and proteases. Our aim is to elucidate how these proteins act in concert to control
the lytic cycle of the parasite and assure infection.
Santos JM, Ferguson DJP, Blackman MJ and Soldati-Favre D (2011) Intramembrane Cleavage of
AMA1 Triggers Toxoplasma to Switch from an Invasive to a Replicative Mode. Science 331:473 -7.
Frénal K, Polonais V, Marq, JB, Stratmann R, Limenitakis J, and Soldati-Favre D (2010) Functional
Dissection of the Apicomplexan Glideosome Molecular Architecture. Cell Host & Microbe
8:343-57.
Daher W., Plattner F, Carlier MF, and Soldati-Favre D (2010) Concerted action of two formins in
gliding motility and host cell invasion by Toxoplasma gondii. PloS Pathogens. 76: e1001132
Sheiner L, Santos JM, Klages N, Parussini F, Jemmely N, Friedrich N, Ward GE, Soldati-Favre D
(2010) Toxoplasma gondii transmembrane microneme proteins and their modular design.
Mol Microbio 77:912-29.
Pino P, Aeby E, Foth BJ, Sheiner L, Soldati T, Schneider A, Soldati-Favre D (2010) Mitochondrial
translation in absence of local tRNA aminoacylation and methionyl tRNA Met formylation
in Apicomplexa. Mol. Microbiol. 76:706-18.
Friedrich N, Santos J, Liu Y, Palma AS, Leon E, Saouros S, Kiso M, Blackman MJ, Matthews S, Feizi
T and Soldati-Favre D (2010) Members of a novel protein family containing microneme
adhesive repeat domains act as sialic acid-binding lectins during host cell invasion by
apicomplexan parasites. J. Biol. Chem. 285: 2064-2076.
Contact: [email protected]
44
Université de Genève • Faculté de médecine
Université de Genève • Faculté de médecine
45
Parasitology
Parasitology
François Chappuis
Department of Community Medicine and Primary Care
Division of International and Humanitarian Medicine (HUG)
Médecins sans Frontières
François Chappuis obtained his Medical Degree in 1997 at the University of Geneva and a PhD
in Medical Sciences in 2008 at the University of Antwerp, Belgium. He obtained the PrivatDocent in 2008 and was nominated as Associate Professor in Humanitarian Medicine in 2012.
He is responsible for a travel and tropical medicine consultation at the HUG and is a medical
adviser for leishmaniasis and trypanosomiasis programmes at Médecins Sans Frontières (MSF).
Improved diagnosis, treatment and control of leishmaniasis and trypanosomiasis
We are focusing our research efforts on improving case-management and control of some of
the most neglected tropical diseases (NTDs) that affect poor communities in Asia, Africa, South
America and Geneva (Latin American migrants). We have validated rapid diagnostic tests (RDT)
for use at point-of-care for visceral leishmaniasis and Chagas disease. On the treatment side,
we have demonstrated the superiority of eflornithine over melarsoprol for the treatment of
advanced African trypanosomiasis, partially clarified the causes of antimonials treatment
failure in patients with cutaneous (Peru) and visceral leishmaniasis (Nepal), and revealed the
high toxicity of nifurtimox in adult patients with Chagas disease. On the control side, we have
shown the lack of efficacy of impregnated bednets on the transmission of visceral
leishmaniasis in Asia.
Jackson Y, Alirol E, Getaz L, Wolff H, Combescure C, Chappuis F (2010) Tolerance and safety of
nifurtimox in patients with chronic Chagas disease. Clin Infect Dis 51: e69-75.
Chappuis F, Mauris A, Holst M, Albajar-Vinas P, Jannin J, Luquetti AO, Jackson Y (2010) Validation
of a rapid immunochromatographic assay for the diagnosis of chronic Chagas disease
among Latin American immigrants in Geneva, Switzerland. J Clin Microbiol 48: 2948-52.
Chappuis F, Sundar S, Hailu A, Ghalib H, Rijal S, Peeling RW, Boelaert M (2007) Visceral
leishmaniasis: what are the needs for diagnosis, treatment and control? Nature Reviews
Microbiol 5: 873-82 and S7-S16.
Chappuis F, Rijal S, Soto A, Menten J, Boelaert M (2006). A meta-analysis of the diagnostic
performance of the direct agglutination test and rK39 dipstick for visceral leishmaniasis,
BMJ 333: 723-7.
Chappuis F, Udayraj N, Stietenroth K, Meussen A, Bovier PA (2005). Eflornithine is safer than
melarsoprol for the treatment of second stage Trypanosoma brucei gambiense human
African trypanosomiasis. Clin Infect Dis 41: 748-51.
Contact: [email protected]
46
Université de Genève • Faculté de médecine
Université de Genève • Faculté de médecine
47
Parasitology
Parasitology
Louis Loutan
Department of Community Medicine and Primary Care
Division of International and Humanitarian Medicine (HUG)
Louis Loutan obtained his medical qualification in 1978. He was appointed Associate Professor
in 2007.
Travel and migration of humans and pathogens
We have explored various aspects of travel and migration medicine ranging from hepatitis A
vaccine (immunogenicity and tolerance), to antimalarial drugs and the epidemiology of
imported infectious diseases by migrants and travelers. We are currently moving into issues
related to globalisation (access to health care, changing epidemiology of infectious diseases
ID in the urban environment, refugee health). Future research directions will strengthen the
links between fundamental parasitology and the clinical context.
Socioeconomic disparities have a great impact on infectious diseases
Alirol E, Getaz L, Stoll B, Chappuis F, Loutan L (2011). Urbanisation and infectious diseases in a
globalised world. Lancet Infect Dis.11:131-41.
Bovier P, Bock J, Farinelli T, Frösner G, Glaus J, Herzog C, Loutan L (2010). Predicted 30-year
protection after vaccination with an aluminium-free virosomal hepatitis A vaccine. J Med
Virol 82:1629-34.
Dahlgren A, DeRoo L, Avril J, Bise G, Loutan L (2009). Health risks ans risk-taking behaviours
among international committee of the red cross (ICRC) expatriate returning from
humanitarian missions. J Trav Med 16:382-390.
Jackson Y, Getaz L, Wolff H, Holst M, Mauris A, Tardin A, Sztajzel J, Besse V, Loutan L, Gaspoz JM
et al. (2010) Prevalence, clinical staging and risk for blood-borne transmission of chagas
disease among latin american migrants in Geneva, Switzerland. PLoS NeglTrop Dis 4:e592.
Chen L, Wilson M, Davis W, Loutan L et al. (2009) Illness in long-term travelers visiting
geosentinel clinics. Emerg Infect Dis 15;1773-1782.
Hatz C, Soto J, Nothdurft HD, Zoller T, Weitzel T, Loutan L, Bricaire F et al. (2008) Treatment of
acute uncomplicated falciparum malaria with artemether-lumefantrine in non-immune
populations : a safety, efficacy, and pharmacokinetic study. Am J Trop Med Hyg 78: 241-247.
Contact: [email protected]
48
Université de Genève • Faculté de médecine
Université de Genève • Faculté de médecine
49
Mycology
Mycology
Martine A. Collart
Department of Microbiology and Molecular Medicine
Martine Collart obtained her PhD in 1990 at the University of Geneva. She continued her
research at Harvard Medical School in Boston with Kevin Struhl, where she identified the NOT
genes using a genetic selection in yeast. In 1993 she started her own independent group to
pursue the characterisation of the Not genes, in the Department of Medical Biochemistry of
the Faculty of Medicine at the University of Geneva. She was appointed Associate Professor in
the Department of Microbiology and Molecular Medicine in 2004 and full Professor in 2011.
Genetic and Biochemical characterisation of the conserved Ccr4-Not complex in yeast
We work on characterising, in the yeast S. cerevisiae, the function of an essential multisubunit
protein complex that is conserved across the eukaryotic kingdom, the Ccr4-Not complex. This
complex has two known enzymatic activities, ubiquitination provided by the RING finger Not4
E3 ligase, and deadenylation provided by the Caf1 and Ccr4 subunits. Despite growing
knowledge on these enzymatic functions, the role of the other subunits, the relationship
between the different subunits and their activities, and the reason for the association of these
different subunits in a complex is unknown. Our more recent experiments suggest that this
complex may serve as a chaperone allowing the assembly of multicomponent complexes in
cells. The tremendous complexity of this system in which a multisubunit complex regulates
assembly of other multisubunit complexes in eukaryotic cells, makes the yeast S. cerevisiae a
perfect model organism for study because of its powerful genetics that can be combined with
biochemistry.
Panasenko OO and Collart MA (2012) Presence of Not5 and ubiquitinated Rps7A in polysome
fractions depends upon the Not4 E3 ligase. Mol. Microbiol. 83: 640-632.
Collart MA and Panasenko OO (2012) The Ccr4-Not complex. Gene 492: 42-53.
Olesya O. Panasenko and Martine A. Collart (2011) Not4 E3 ligase contributes to proteasome
assembly and functional integrity via the Ecm29 chaperone. Mol. Cell. Biol. 31: 1610-1623.
Azzouz N, Panasenko OO, Colau G and Collart MA (2009) The Ccr4-Not complex physically and
functionally interacts with TRAMP and the nuclear exosome. PLoS One 4:e6760.
Panasenko OO, David F and Collart MA (2009) Ribosome association and stability of the nascent
polypeptide-associated complex is dependent upon its own ubiquitination. Genetics 181:
447-460.
Contact: [email protected]
50
Université de Genève • Faculté de médecine
Université de Genève • Faculté de médecine
51
Host Response
Host Response
Alain Gervaix
Department of Pediatrics
Alain Gervaix obtained his medical degree at the University of Geneva in 1986, then specialty
qualifications in Paediatrics in 1994 and in Infectiology in 1999. He spent two years at the
University of San Diego, California, USA as a Postdoctoral Research Fellow and came back to
the HUG as the Head of the Paediatric Infectious Disease and Emergency Division. He was
appointed Associate Professor in 2006 and full Professor in 2012. Since 2011 he has been ViceDean of the Faculty.
Inflammatory markers in bacterial infection
Our group works mainly on the value of inflammatory markers such as procalcitonin and
C-reactive protein in the prediction of serious bacterial infection in young children with fever
without source.
Procalcitonin is a 116 amino acid protein produced by multiple organs in response to bacterial
challenge. Investigations performed in fever without source, pyelonephritis, meningitis and
pneumonia have shown that this protein is superior to other blood markers in predicting a
bacterial infection. We recently validated and published a biological score based on the results
of procalcitonin, C-reactive protein and urine dispstick to help physicians in the diagnosis of
severe infections in children less than 3 years of age.
Galetto-Lacour A, Zamora SA, Andreola B, Bressan S, Lacroix L, Da Dalt L, Gervaix A (2010).
Validation of a laboratory risk index score for the identification of severe bacterial infection
in children with fever without source. Arch Dis Child. 95:968-73.
Lacour AG, Zamora SA, Gervaix A (2008). A score identifying serious bacterial infections in
children with fever without source. Pediatr Infect Dis J. 27:654-6.
Leroy S, Romanello C, Galetto-Lacour A, et al. (2007) Procalcitonin to reduce the number of
unnecessary cystographies in children with a urinary tract infection: a European validation
study. J Pediatr. 150:89-95.
Galetto-Lacour A, Zamora SA, Gervaix A (2003). Bedside procalcitonin and C-reactive protein
tests in children with fever without localizing signs of infection seen in a referral center.
Pediatrics. 112:1054-60.
Gervaix A, Galetto-Lacour A, Gueron T, et al. (2001) Usefulness of procalcitonin and C-reactive
protein rapid tests for the management of children with urinary tract infection. Pediatr
Infect Dis J. 20:507-11.
Contact: [email protected]
52
Université de Genève • Faculté de médecine
Université de Genève • Faculté de médecine
53
Host Response
Host Response
Klara Posfay-Barbe
Department of Pediatrics
Klara Posfay Barbe obtained her MD in 1994 at the University of Geneva. After intensive training
in pediatrics at the HUG, she followed from 2001 to 2004 a postdoctoral training in paediatric
infectious diseases and clinical research at the University of Pittsburgh Medical Center, USA.
In 2004 she returned to the Department of Paediatrics in Geneva where she was appointed
Cheffe de Clinique Scientifique in 2004 and Médecin Adjoint in 2009. In 2011, she obtained her
Privat-Docent. She is currently Head of the Department of Paediatric Infectious Diseases.
Immune responses to infection in children
Our group mostly studies antibody responses against well known antigens such as varicella or
Haemophilus influenzae in different settings (immunocompromised children, very young
infants), or against “new” bacteria (such as Parachlamydiae spp.). We are also interested in new
antigens present on Streptococcus pneumoniae, such as pneumococcal surface proteins (PcpA,
PhtD, PrtA, LytB), which elicit antibody responses after disease or carriage. These antigens,
which are conserved across all pneumococcal serotypes, could be used in the future to develop
new vaccines. Finally, we also study innate immunity by measuring the effect of pneumococcal
infection on the cellular expression of Toll-like receptors in children with recurrent lower
respiratory tract infections.
.
Fold-increase of anti-pneumococcal surface protein (PSP) antibody concentrations
in bacteraemic children. The ratio of convalescent to acute anti-PSP antibody geometric
mean concentration (GMC) is illustrated for each PSP and age group. PcpA,
pneumococcal choline-binding protein A; PhtD, pneumococcal histidine triad D; PrtA,
serine proteinase precursor A. (Hagerman et al., 2011)
Schäppi MG, Meier S, Bel M, Siegrist CA, Posfay-Barbe KM (2012), the H1N1 Study Group.
Protective Antibody Responses to Influenza A/H1N1/09 Vaccination in Children with Celiac
Disease. J Pediatr Gastroenterol Nutr. 54:817-819
L’Huillier AG, Wildhaber BE, Belli DC, Diana A, Rodriguez M, Siegrist CA, Posfay-Barbe KM (2012).
Successful serology-based intervention to increase protection against vaccine-preventable
diseases in liver-transplanted children: A 19-yr review of the Swiss national reference center.
Pediatr Transplant. 16:50-7
Hagerman A, Posfay-Barbe KM, Grillet S, Ochs MM, Brookes RH, Greenberg D, Givon-Lavi N,
Dagan R, Siegrist CA (2011). Failure to elicit seroresponses to pneumococcal surface proteins
18:756-62
Lienard J, Croxatto A, Aeby S, Jaton K, Posfay-Barbe K, Gervaix A, Greub G (2011). Development
of a new Chlamydiales-specific real-time PCR and its application to respiratory clinical
samples. J Clin Microbiol. 49:2637-42.
Posfay-Barbe KM, Kobela M, Sottas C, Grillet S, Taguebue J, Ekoe T, Lambert PH, Lecoultre C,
Siegrist CA (2010). Frequent failure of adolescent booster responses to tetanus toxoid
despite infant immunization: waning of infancy-induced immune memory? Vaccine
28:4356-61
Contact: [email protected]
54
Université de Genève • Faculté de médecine
Université de Genève • Faculté de médecine
55
Host Response
Host Response
Marc Chanson
Department of Pediatrics
Marc Chanson obtained his PhD in 1991 at the University of Geneva. From 1991 to 1993 he was
Post Doctoral Fellow at the Albert Einstein College of Medicine, Department of Neurosciences,
in New York. Before his return to Geneva in 1995 he was postdoctoral Fellow at the Department
of Physiology at the University of Utrecht. He was nominated Lecturer in 2002 and Associate
Professor in 2012.
Gap junctional intercellular communication in cystic fibrosis airway disease
We are studying the regulation and function of gap junction channels in normal and inflamed
lungs. Gap junctions interconnect ciliated airway epithelial cells that constitute the physical
barrier between the host and the environment. In cystic fibrosis (CF), mutations of the cystic
fibrosis transmembrane conductance regulator (CFTR), which is expressed in ciliated cells, alters
the airway epithelium barrier. This impaired defence is associated with chronic infection and
inflammation of the lung, leading to progressive loss of respiratory function. However, the links
between the genetic defect in CF and initiation of the chronic infection of the airways are poorly
known. We have found that CFTR regulates the activity of gap junction channels and that gap
junctional intercellular communication contributes to the defence mechanisms of airway
epithelial cells to infection. More recently, we have observed that quorum sensing molecules
produced by opportunistic pathogens in CF (Pseudomonas aeruginosa, Staphylococcus aureus)
interfere with the function of gap junctions in airway epithelial cells. Further studies aim at
the analysis of the underlying mechanisms and at understanding the consequence of gap
junction channel deregulation in the pathogenesis of CF.
A human airway epithelial cell surrounded
by Pseudomonas aeruginosa (in red) and expressing
the apoptotic marker AnnexinV (in green).
Losa D, Chanson M, Crespin S (2011). Connexins as therapeutic targets in lung disease. Expert
Opinion on Therapeutic Targets 15:989-1002
Scheckenbach KEL, Losa D, Crespin S, Dudez T, Bacchetta M, O’Grady S, Chanson M (2011). PGE2
regulation of CFTR activity and airway surface liquid volume requires gap junctional
communication. Am J Respir Cell Mol Biol 44:74-82.
Sarieddine MZ, Garcia I, Foglia B, Kwak BR, Chanson M (2009). Targeting Connexin43 protects
against acute lung inflammation. J Cell Mol Med 13: 4560-4570.
Huang S, Dudez T, Scerri I, Thomas MA, Giepmans BNG, Suter S, Chanson M (2003). Defective
activation of c-Src in CF airway epithelial cells results in loss of TNF-α-induced gap junction
regulation. J Biol Chem 278: 8326-8832.
Chanson M, Scerri I, Suter S (1999). Defective regulation of gap junctional coupling in cystic
fibrosis pancreatic duct cells. J Clin Invest 103: 1677-1684.
Contact: [email protected]
56
Université de Genève • Faculté de médecine
Université de Genève • Faculté de médecine
57
Host Response
Host Response
Irene Garcia-Gabay
Department of Pathology and Immunology
Irene Garcia-Gabay obtained her PhD in immunology at the University of Geneva (1982). After
a Fellowship at the Pasteur Institute, Paris, France, she did postdoctoral work at the Swiss
Institute for Experimental Cancer Research (ISREC), Department of Molecular Biology. In 1994,
she was a recipient of funds from the Marie Heim-Vögtlin programme from the SNSF and
established her laboratory. She is Lecturer and Research Associate at the Department of
Pathology and Immunology.
Host defence mechanisms against mycobacterial infections
Our laboratory is interested in host resistance to Mycobacterium tuberculosis and M. bovis BCG
infections. We are working on cellular mediators such as cytokines involved in innate and
adaptive immunity to control these intracellular pathogens. We have long experience of Tumor
Necrosis Factor (TNF), a pro-inflammatory cytokine activated by mycobacteria in macrophages
and T cells, which plays a critical role in granuloma formation and protection against
mycobacteria. On the other hand, TNF is a main target for the treatment of inflammatory
diseases and its inhibition may reactivate latent tuberculosis. We are evaluating the activity of
the different TNF molecules and interactions with soluble and membrane-bound TNF receptors,
to define the regulatory mechanisms involved in both host protection and inflammatory
disorders in order to dissociate these two activities and propose new strategies of intervention
in inflammation and infection.
Olleros ML, Vesin D, Bisig R, Santiago-Raber ML, Schuepbach-Mallepell S, Kollias G, Gaide O and
Garcia I (2012) Membrane-bound TNF induces protective immune responses to M. bovis BCG
infection: regulation of memTNF and TNF receptors comparing two memTNF molecules.
PLoS ONE 7:e31469
Garcia I, Olleros ML, Quesniaux VF, Jacobs M, Allie N, Nedospasov SA, Szymkowski DE, Ryffel B
(2011) Roles of soluble and membrane TNF and related ligands in mycobacterial infections :
effects of selective and non-selective TNF inhibitors during infection. Adv Exp Med Biol
691:187-201.
Olleros ML, Vesin D, Fotio AL, Santiago-Raber ML, Tauzin S, Szymkowski DE, Garcia I (2010)
Soluble TNF, but not membrane TNF, is critical in LPS-induced hepatitis. J. Hepatol. 53:10591068.
Allie N, Keeton R, Court N, Abel B, Fick L, Vasseur V, Vacher R, Olleros ML, Drutskaya MS, Guler G,
Nedospasov SA, Garcia I, Ryffel B, Quesniaux VF, Jacobs M (2010) Limited role for
lymphotoxin a in the host immune response to Mycobacterium tuberculosis. J. Immunol.
185:4292-301.
Olleros ML, Vesin D, Lambou AF, Janssens JP, Ryffel B, Rose S, Frémond C, Quesniaux VF,
Szymkowski DE and Garcia I (2009) Dominant-Negative TNF Protects from Mycobacterium
bovis BCG and Endotoxin-Induced Liver Injury Without Compromising Host Immunity to
BCG and M. tuberculosis. J. Infectious Diseases, 199:1053-63.
Contact: [email protected]
58
Université de Genève • Faculté de médecine
Université de Genève • Faculté de médecine
59
Host Response
Host Response
Pierre Cosson
Department of Cell Physiology and Metabolism
Pierre Cosson obtained his PhD in Immunology at the University of Marseille (1990). He spent
two years as a Postdoctoral Fellow at the National Institutes of Health, Bethesda, USA, and
then joined the Basel Institute of Immunology (Basel, CH) as an independent researcher. He
was awarded an Swiss National Science Foundation START Fellowship in 1997 and joined the
Geneva Faculty of Medicine, where he was later appointed Associate Professor (2002) and full
Professor (2009) at the Departement of Cell Physiology and Metabolism. Since 2009, Pierre
Cosson has held the Doerenkamp- Naef-Zbinden Chair for the development of alternatives to
animal experiments.
Dictyostelium amoebae: a model to study host-pathogen interactions
Our group makes use of Dictyostelium amoebae as a model to study interactions between
phagocytic cells and bacteria. This genetically tractable model allows us to study cellular
mechanisms such as cell adhesion, phagocytosis and intracellular killing. Bacterial
pathogenicity mechanisms can also be studied advantageously using this simple model.
A Dictyostelium amoeba (white and green) ingesting
a bacterium (red). The amoeba is trying to kill
the bacteria, the bacteria is trying to kill the amoeba.
Who is going to win?
Le Coadic M, Simon M, Marchetti A, Ebert D, Cosson P (2012) Daphnia magna, a host to evaluate
bacterial virulence. Appl. Environ. Microbiol. 78:593-5.
Lelong E, Marchetti A, Simon M, Burns JL, van Delden C, Köhler T, Cosson P (2011) Evolution of
Pseudomonas aeruginosa virulence in infected patients revealed in a Dictyostelium
discoideum host model. Clin. Microb. Infect. 17:1415-20.
Lelong E, Marchetti A, Guého A, Lima WC, Sattler N, Molmeret M, Hagedorn M, Soldati T, Cosson
P (2010) Role of magnesium and a phagosomal P-type ATPase in intracellular bacterial
killing. Cell. Microb. 13:246-58.
Froquet R, Lelong E, Marchetti A, Cosson P (2009) Dictyostelium discoideum: a model host to
measure bacterial virulence. Nature Protocols. 4:25-30.
Alibaud L, Köhler T, Coudray A, Prigent-Combaret C, Bergeret E, Perrin J, Benghezal M, Reimmann
C, Gauthier Y, van Delden C, Attree I, Fauvarque MO, Cosson P (2008) Pseudomonas
aeruginosa virulence genes identified in a Dictyostelium host model. Cell. Microb. 10:729-40.
Benghezal M, Fauvarque MO, Tournebize R, Froquet R, Marchetti A, Bergeret E, Lardy B, Klein G,
Sansonetti P, Charette SJ, Cosson P (2006) Specific host genes required for the killing of
Klebsiella bacteria by phagocytes. Cell. Microb. 8:139-48.
Contact: [email protected]
60
Université de Genève • Faculté de médecine
Université de Genève • Faculté de médecine
61
Host Response
Host Response
Jérôme Pugin
Department of Anaesthesiology, Pharmacology and Intensive Care
Department of Microbiology and Molecular Medicine
Jérôme Pugin obtained his MD degree in 1984 in Geneva, and later specialised in both Internal
and Intensive Care medicine. He shares his time between clinical work as a Deputy Head
Physician of the Intensive Care Division at Geneva University Hospitals, and research in the
Department of Microbiology and Molecular Medicine at the Faculty of Medicine of the
University of Geneva. He spent three years between 1991 and 1994 in the Department of
Immunology of the Scripps Research Institute in La Jolla, USA. Jérôme Pugin was appointed
Associate Professor in 2007 and full Professor in 2012 at the Faculty of Medicine of Geneva.
Since 2011 he has been Vice-Dean of the Faculty.
LPS induced TLR4 clustering
Recognition of bacteria by innate immunity receptors
Our research interests have focused over the last 20 years on the molecular and cellular
pathogenesis of sepsis. In particular, we have worked on soluble proteins involved in the innate
recognition of bacteria such as soluble CD14 and MD-2, as well as in the Toll-like receptors
activated by Gram-negative and Gram-positive bacteria. Another area of study is the molecular
pathogenesis and cell signaling of ventilator-induced lung injury, and lung inflammation in
the context of acute respiratory distress syndrome. We have also identified and tested
biomarkers in the field of clinical sepsis.
Dunn-Siegrist I, Tissières P, Drifte G, Bauer J, Moutel S, Pugin J (2012) Toll-like Receptor Activation
of Human Cells by Synthetic Triacylated Lipid A-like Molecules. J Biol Chem. 287: 16121-31
Tissières P, Ochoda A, Dunn-Siegrist I, Drifte G, Morales M, Pfister R, Berner M, Pugin J (2012)
Innate immune deficiency of extremely premature neonates can be reversed by interferon-γ.
PLoS One 7: e32863
Tissières P, Araud T, Ochoda A, Drifte G, Dunn-Siegrist I, Pugin J (2009) The expression of the
acute phase MD-2 gene depends on the cooperation between PU.1 and C/EBP ß. J. Biol.
Chem. 284: 26261-72
Tissières P, Dunn-Siegrist I, Comte R, Nobre V, Pugin J (2008) Soluble MD-2 is an acute phase
protein and an opsonin for Gram-negative bacteria. Blood 111: 2122-31
Pugin J, Dunn-Siegrist I, Dufour J, Tissières P, Charles PE, Comte R (2008) Cyclic stretch of human
lung cells induces an acidification and promotes bacterial growth. Am. J. Respir. Cell Mol.
Biol. 38:362-70
Elson G, Dunn-Siegrist I, Daubeuf B, Pugin J (2007) Contribution of Toll-like receptors to the
innate immune response to Gram-negative and Gram-positive bacteria. Blood 109:1574-8
Pugin J, Stern-Voeffray S, Daubeuf B, Matthay MA, Elson G, Dunn-Siegrist I (2004) Soluble MD2 activity in plasma from patients with severe sepsis and septic shock. Blood 104: 4071-4079
Contact: [email protected]
62
Université de Genève • Faculté de médecine
Université de Genève • Faculté de médecine
63
Host Response
Host Response
Karl-Heinz Krause
Department of Pathology and Immunology
Karl-Heinz Krause obtained his medical degree in 1984 at the University of Munich, where he
also trained in internal medicine. After Fellowships at the Geneva University Hospitals (198487) and the University of Iowa Hospitals, USA (1987-89), he was recruited as a junior faculty
member in Geneva. He was appointed Associate Professor in 1998 and full Professor in 2001 at
the Department of Internal medecine and Geriatrics. Since 2005 he has been affiliated to the
Department of Pathology and Immunology, as well as the Department of Genetic and
Laboratory Medicine , HUG.
NADPH oxidases
Reactive oxygen species (ROS) are a doubled-edged sword. They have crucial physiological
functions, from host defence to participation in biosynthetic processes and from intracellular
signaling to regulation of gene expression. However, they can also be destructive and are linked
to many disease processes. The NOX family of NADPH oxidases are one of the major sources
of ROS and our laboratory is particularly interested in this enzyme family. ROS-generating NOX
enzymes are a phylogenetically ancient system found in many unicellular organisms. They have
a range of complex functions in multicellular organisms, notably a role in host defence and
inflammation. Much has been learned from patients with chronic granulomatous diseases
(genetic NOX2 deficiency), diseases characterised by the concommitant occurence of immune
deficiency and hyperinflammation.
Neural differentiation of pluripotent stem cells
A second focus of our laboratory is neuronal differentiation of pluripotent stem cells. Such
differentiation protocols can be used to generate in vitro human neural cells and tissues. This
is particularly relevant for the creation of human model systems for diseases of the central
nervous system. Among others, we are using the system to study viral infection of the human
CNS. Also, we are working on the response to tumour invasion of human neural tissues, which
in many respects can mimic antiviral responses.
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Université de Genève • Faculté de médecine
Sorce S, Schiavone S, Tucci P, Colaianna M, Jaquet V, Cuomo V, Dubois-Dauphin M, Trabace L,
and Krause KH (2010) The NADPH oxidase NOX2 controls glutamate release: a novel
mechanism involved in psychosis-like ketamine responses. J Neurosci. 30:11317-25.
Li B, Bedard K, Sorce S, Hinz B, Dubois-Dauphin M, Krause KH (2009) NOX4 expression in human
microglia leads to constitutive generation of reactive oxygen species and to constitutive
IL-6 expression. Journal of Innate Immunity 1:570-581.
Bedard K, Attar H, Bonnefont J, Jaquet V, Borel C, Plastre O, Stasia MJ, Antonarakis SE, Krause
KH (2009) Three common polymorphisms in the CYBA gene form a haplotype associated
with decreased ROS generation. Hum Mutat 30:1123-33.
Schäppi M, Deffert C, Fiette L, Gavazzi G, Herrmann F, Belli D, Krause KH (2008) Branched fungal
beta-glucan causes hyperinflammation and necrosis in phagocyte NADPH oxidasedeficient mice. J Pathol. 214:434-44.
Bedard K, Krause KH (2007) The NOX family of ROS-generating NADPH oxidases: physiology
and pathophysiology. Physiol Reviews 87(1):245-313.
Contact: [email protected]
Université de Genève • Faculté de médecine
65
Vaccinology
Vaccinology
Claire-Anne Siegrist
Departments of Pathology and Immunology
Department of Pediatrics
WHO Collaborative Center for Vaccine Immunology
Claire-Anne Siegrist graduated in 1983. She trained in paediatrics, infectious diseases and
immunology prior to dedicating her professional life to all aspects of vaccinology. Associate
Professor of Vaccinology (2000) and full Professor of Paediatrics (2006), she is President of the
Swiss National Advisory Committee on Immunization (2004), member of the UK National
Committee (2008) and of the WHO Strategic Advisory Group of Experts on Immunization
(2010). She leads the InfoVac expert network (www.infovac.ch), has developed vaccinology
clinical decision support software for health care professionals (www.viavac.ch), and is the
founder of the Swiss Electronic Vaccination Record (www.myvaccines.ch)..
Vaccine immunology from early life to vaccine safety
Our research focusses on i) neonatal immunology in order to understand the postnatal
development process of the immune system and how it is regulated to control early life
immune responses to foreign antigens; ii) vaccine immunology through which we study the
mode of action of current and novel vaccines to identify strategies capable of strengthening
immune competence, especially in the very young and iii) clinical vaccinology to understand
the determinants of vaccine responses in patients with varying levels of immune competence
because of age, underlying disease or immunosuppression, and thus identify optimal
strategies.
Siegrist CA, van Delden C, Bel M, Combescure C, Delhumeau C, Cavassini M, Clerc O, Meier S,
Hadaya K, Soccal PM, Yerly S, Kaiser L, Hirschel B and A. Calmy (2012) Higher memory
responses in HIV-infected and kidney transplanted patients than in healthy subjects
following priming with the pandemic vaccine. Plos One 7:e40428
Kamath AT, Mastelic B, Christensen D, Rochat AF, Agger EM, Pinschewer DD, Andersen P,
Lambert PH and Siegrist CA (2012) Synchronization of DC activation and antigen exposure
is required for the induction of Th1/Th17 responses. J Immunol. 188:4828-37
Belnoue E, Tougne C, Rochat AF, Lambert PH, Pinschewer DD and Siegrist CA (2012) Homing and
adhesion patterns determine the cellular composition of the bone marrow plasma cell
niche. J Immunol. 188:1283-91.
Gabay C, Bel M, Combescure C, Ribi C, Meier S, Posfay-Barbe K, Grillet S, Seebach JD, Kaiser L,
Wunderli W, Guerne PA and Siegrist CA (2011) Impact of synthetic and biological disease
modifying antirheumatic drugs on antibody responses to the ASO3-adjuvanted pandemic
influenza vaccine. Arthritis & Rheumatism 63:1486-96.
Kamath AT, Rochat AF, Christensen D, Agger EM, Andersen P, Lambert PH, Siegrist CA. A
Liposome-based mycobacterial vaccine induces potent adult and neonatal multifunctional
T cells through the exquisite targeting of dendritic cells. PLoS One 4:e5771
Kamath AT, Rochat AF, Valenti MP, Agger EM, Lingnau K, Andersen P, Lambert PH, Siegrist CA
(2008) Adult-like anti-mycobacterial T cell and in vivo dendritic cell responses following
neonatal immunization with Ag85B-ESAT-6 in the IC31 adjuvant. PLoS ONE 3:e3683.
Belnoue E, Pihlgren M, McGaha TL, Tougne C, Rochat AF, Bossen C, Schneider P, Huard B, Lambert
PH, Siegrist CA (2008) APRIL is critical for plasmablast survival in the bone marrow and
poorly expressed by early life bone marrow stromal cells. Blood 111:2755-64.
Contact: [email protected]
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Université de Genève • Faculté de médecine
Université de Genève • Faculté de médecine
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Dental Bacteriology
Dental Bacteriology
Serge Bouillaguet
Division of Cariology and Endodontics
Serge Bouillaguet obtained his dental degree in 1983 and his Doctorate in Dental Surgery in
Marseilles in 1984. He obtained a Doctorate in Medical Dentistry at the University of Geneva
in 1989 and his Privat-Docent in 2003. He was appointed Lecturer in 2001 and appointed
Associate Professor in 2011.
Blue light-mediated inactivation of endodontic pathogens
Our research interests focus on the evaluation of current antimicrobial strategies used in
endodontics together with the development of new approaches based on the photoinactivation of endodontic pathogens. We have identified different photosensitisers which can
be activated with conventional light curing units used in dental offices. We work on biofilm
models using plastic or glass surfaces, membranes or dentin disks. Biofilm formation and
growth are monitored by LIVE/DEAD fluorescence microscopy to simultaneously detect intact
cells and dead/injured ones. The expression virulence genes after treatment is also evaluated
by PCR.
In addition our group has routinely used cytotoxicity assays to evaluate the short or long term
biological response of cultured cells (host cells) exposed to various disinfecting agents and
endodontic biomaterials. We are assessing inflammatory reactions and oxidative stress induced
by blue light-activated photosensitisers and the likelihood of lethal damage to resident cells
resulting from such stress.
Pileggi G, Wataha JC, Girard M, Grad I, Schrenzel J, LangeN, Bouillaguet S (2012) Blue lightmediated inactivation of Enterococcus faecalis in vitro. PhotoDiag PhotoTherapy (in press)
Grad I, Hibaoui Y, Jaconi M, Chicha L, Bergström-Tengzelius R, Sailani MR, Pelte MF, Dahoun S,
Mitsiadis TA, Töhönen V, Bouillaguet S, Antonarakis SE, Kere J, Zucchelli M, Hovatta O, Feki
A (2011) NANOG priming before full reprogramming may generate germ cell tumours. Eur
Cell Mater; 22:258-74
Brackett MG, Messer RL, Lockwood PE, Bryan TE, Lewis JB, Bouillaguet S, Wataha JC (2010)
Cytotoxic response of three cell lines exposed in vitro to dental endodontic sealers. J Biomed
Mater Res B Appl Biomater. 95:380-6.
Bouillaguet S, Wataha JC, Zapata O, Campo M, Lange N, Schrenzel J (2010) Production of reactive
oxygen species from photosensitizers activated with visible light sources available in dental
offices. Photomed Laser Surg. 28:519-25.
Bronnec F, Bouillaguet S, Machtou P (2010) Ex vivo assessment of irrigant penetration and
renewal during the final irrigation regimen. Int Endod J. 43:663-72.
Bronnec F, Bouillaguet S, Machtou P (2010) Ex vivo assessment of irrigant penetration and
renewal during the cleaning and shaping of root canals: a digital subtraction radiographic
study. Int Endod J. 43:275-82.
Bouillaguet S, Owen B, Wataha JC, Campo MA, Lange N, Schrenzel J (2008) Intracellular reactive
oxygen species in monocytes generated by photosensitive chromophores activated with
blue light. Dent Mater. 24:1070-6.
Contact: [email protected]
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Université de Genève • Faculté de médecine
Université de Genève • Faculté de médecine
69
Dental Bacteriology
Dental Bacteriology
Andrea Mombelli
Division of Periodontology and Oral Pathophysiology
Andrea Mombelli graduated from the University of Bern School of Dental Medicine and
completed his post-graduate studies reaching the status of Privat-Docent in 1992. He has a
Swiss Federal Diploma in Dentistry, a Doctorate in Dentistry (Dr. med. dent.) and is a Swiss FMHcertified periodontist. Before being appointed as Professor and Head of the Division of Oral
Physiopathology and Periodontology, School of Dental Medicine of the Medical Faculty, he held
the position of Head of the Laboratory for Oral Microbiology at the University of Bern School
of Dental Medicine (1992-1999). Andrea Mombelli was associate Vice-Dean from 2005 to 2011.
Antibiotic therapy as adjunct to periodontal treatment: effect of different timing on
clinical, microbiological and systemic response
A beneficial effect of adjunctive systemic antibiotics on the clinical outcome of periodontal
therapy has been shown, but many questions remain with regard to their optimal use and the
specific relationship of benefit and risk. In the context of this large RCT we study changes in
the oral microbiota related to variation in the treatment protocol. Analyses focus on resistance
development and diagnostic and prognostic utility of microbiological parameters.
Mombelli, A., Cionca, N., Almaghlouth, A., Décaillet, F., Courvoisier, D.S. & Giannopoulou, C.
(2012) Are there specific benefits of amoxicillin-metronidazole in Aggregatibacter
actinomycetemcomitans-associated periodontitis? Double blind, randomized clinical trial
of efficacy and safety. J. Periodontol DOI: 10.1902/jop.2012.120281
Cionca N, Giannopoulou C, Ugolotti G & Mombelli A (2010) Microbiologic testing and outcomes
of full-mouth scaling and root planing with or without Amoxicillin/Metronidazole in
chronic periodontitis. J. Periodontol. 81: 15-23
Mombelli A & Décaillet F (2011) The characteristics of biofilms in peri-implant disease. J. Clin.
Periodontol. 38: 203-213
Mombelli A, Cionca N & Almaglouth A (2011) Does adjunctive antimicrobial therapy reduce the
perceived need for periodontal surgery? Periodontology 2000 55: 205-216
Cappuyns I, Cionca N, Wick P, Giannopoulou C & Mombelli A (2012) Treatment of residual
pockets with photodynamic therapy, diode laser or deep scaling. A randomized, split-mouth
controlled clinical trial. Lasers Med. Sci. DOI: 10.1007/s10103-011-1027-6.
Contact: [email protected]
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Université de Genève • Faculté de médecine
Université de Genève • Faculté de médecine
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Hygiene and Infection control
Hygiene and Infection control
Didier Pittet
Infection Control Programme, HUG
Didier Pittet obtained his medical degree in 1983 on “Inositol phosphates and cellular
activation” from the University of Geneva Faculty of Medicine, and is specialised in infectious
diseases, hospital epidemiology and public health. In 1992 he became Head of the Infection
Control and Prevention Programme at the HUG and Faculty of Medicine. In 2008, the
Programme was designated a WHO Collaborating Centre on Patient Safety. He was appointed
Associate Professor at the Faculty of Medicine in 2000 and promoted to full Professor in 2010.
He has received several degrees and awards for his work as External Lead of the WHO First
Global Patient Safety Challenge “Clean Care Is Safer Care” initiative and is an international
expert for the WHO.
Prevention and control of healthcare-associated infection and antimicrobial
resistance: local, national, and global perspectives
MRSA and multidrug resistance. We are conducting various cohort studies to evaluate the value
of screening and decolonisation to decrease MRSA transmission, including several
epidemiological studies to address the emerging threat of community MRSA.
Innovative strategies in infection control and prevention. Our group is developing and testing
innovative multidisciplinary and multifaceted approaches to prevent or contain healthcareassociated infection, including microbiological aspects of transmission.
“Clean Care is Safer Care”. As a WHO Collaborating Centre on Patient Safety and in association
with WHO Patient Safety, we focus on the evaluation of the burden of healthcare-associated
infection with the aim of identifying and implementing the most feasible and effective
solutions/measures for prevention worldwide. The strategy is currently endorsed by two-thirds
of the United Nations’ Member States.
Longtin Y, Sax H, Allegranzi B, Schneider F, Pittet D (2011) Videos in clinical medicine: hand
hygiene. New Engl JMed 364:e24.
Harbarth S, Fankauser C, Schrenzel J, Christenson J, Gervaz P, Bandiera-Clerc C, Renzi G, Vernaz
N, Sax H, Pittet D (2008) Universal screening for methicillin-resistant Staphylococcus aureus
at hospital admission and nosocomial infection in surgical patients. JAMA 299:1149-1157.
Pittet D, Donaldson L (2005) Clean Care is Safer Care: a worldwide priority. Lancet 366:12461247.
Pittet D, Hugonnet S, Harbarth S, Mourouga P, Sauvan V, Touveaneau S, Perneger TV (2000)
Effectiveness of a hospital-wide programme to improve compliance with hand hygiene.
Lancet 356:1307-1312.
Eggimann P, Harbarth S, Constantin M-N, Touveneau S, Chevrolet JC, Pittet D (2000) Impact of
a prevention strategy targeted at vascular-access care on incidence of infections in intensive
care. Lancet 355:1864-1868.
Contact: [email protected]
Infections in orthopaedic surgery and traumatology. Our research seeks to identify novel
strategies for the diagnosis, prevention and treatment of osteoarticular infections.
Determinants and prevention of healthcare-associated infections in adult and paediatric
critical care. We are investigating risk factors associated with device-associated infections in
order to identify novel prevention strategies.
Epidemiology of noma in Niger. Our research focuses on the risk factors for noma and
compares oral bacterial diversity of children with noma and controls from the same region.
Prevention strategies will be tested following results of the current research.
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Université de Genève • Faculté de médecine
Université de Genève • Faculté de médecine
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Hygiene and Infection control
Hygiene and Infection control
Stephan Harbarth
Infection Control Programme, HUG
Stephan Harbarth earned his medical degree from Ludwig-Maximilians-University in Munich
in 1993, Germany, and completed his residency in internal medicine and tropical medicine at
Munich University Hospitals. After serving as a Clinical Fellow in the Infectious Diseases
Division and Infection Control Programme in the Department of Internal Medicine at Geneva
University Hospitals, Dr Harbarth completed his Master degree in epidemiology at Harvard
University. He is board-certified (FMH) in infectious diseases and was appointed Associate
Professor in 2010. Dr Harbarth’s work has garnered several awards, including the ICAAC Young
Investigator Award from ASM (2003), the Young Investigator Award from ESCMID (2006), the
Swiss Society for Infectious Diseases Award for epidemiological research (2008), and the SHEA
Investigator Award in 2011.
Proportion of consultations at office-based doctors for a specific diagnosis resulting
in antibiotic prescriptions in France, 1984-2009.
Control of MRSA and multidrug-resistance
Over the last two decades many institutions around the globe have experienced hyperendemic
multidrug-resistant microorganisms such as MRSA and ESBL-producing enterobacteriacae. Our
group is currently conducting several clinical and epidemiological studies to evaluate key
questions related to the control of acquisition, transmission and infection by multidrugresistant microorganisms. We participate in several large-scale European studies (MOSAR,
SATURN, R-GNOSIS, Rapp-ID, AIDA) to address this important public health threat. We
collaborate closely with the Genomics Research Laboratory at HUG, based on a productive
translational research platform. The most notable examples of our research are the evaluation
of a rapid molecular MRSA test evaluated in a large interventional cohort study (JAMA 2008),
the advanced statistical analysis of epidemiologic trends in multiresistant microorganisms (JAC
2008 and JAC 2011), the conduct of epidemiologic studies linking patient data with molecular
investigations (J Clin Microbiol 2011; Clin Infect Dis 2011), the evaluation of antibiotic
stewardship interventions (Lancet Infect Dis 2010, JAC 2011) and several currently ongoing
placebo-controlled, randomised clinical trials to decolonise MRSA and ESBL carriers.
Chahwakilian P, Huttner B, Schlemmer B, Harbarth S (2011) Impact of the French campaign to
reduce inappropriate ambulatory antibiotic use on the prescription and consultation rates
for respiratory tract infections. J Antimicrob Chemother 66: 2872-9.
Lee AS, Macedo M, François P, Renzi G, Schrenzel J, Vernaz N, Pittet D, Harbarth S (2011) Impact
of Combined Low-Level Mupirocin and Chlorhexidine Resistance on Persistent MRSA
Carriage after Decolonization Therapy: A Case-Control Study. Clin Infect Dis 52: 1422–1430.
De Angelis G, François P, Lee A, Schrenzel J, Renzi G, Girard M, Pittet D, Harbarth S (2011)
Molecular and Epidemiological Evaluation of Strain Replacement in Patients Previously
Harboring Gentamicin-Resistant MRSA. J Clin Micro 49: 3880-84.
Longtin Y, Sudre S, François P, Schrenzel J, Aramburu C, Pastore R, Gervaix A, Renzi G, Pittet D,
Harbarth S (2009) Community-associated methicillin-resistant Staphylococcus aureus: Risk
factors for infection and long-term follow-up. Clin Microbiol Infect 15: 552–559. Harbarth S, Fankhauser C, Schrenzel J, Christenson J, Gervaz P, Bandiera-Clerc C, Renzi G, Vernaz
N, Sax H, Pittet D (2008) Universal screening for methicillin-resistant Staphylococcus aureus
at hospital admission and nosocomial infection in surgical patients. JAMA 299: 1149-1157.
Albrich WC, Harbarth S (2008) Healthcare personnel: Source, vector or victim of MRSA? LANCET
Infectious Diseases 8: 289-311. Contact: [email protected]
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Université de Genève • Faculté de médecine
Université de Genève • Faculté de médecine
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Hygiene and Infection control
Hygiene and Infection control
Benedetta Allegranzi
Infection Control Programme, HUG
WHO “Clean Care is Safer Care” Programme
Benedetta Allegranzi obtained her medical degree in 1994 in Verona, Italy, and her postgraduate degree in infectious diseases and tropical medicine in 1998. She came to Geneva in
2005 as a Consultant at the World Health Organization. She is currently Team Leader of the
“Clean Care is Safer Care” programme at WHO HQ/PSP/IER. Dr Allegranzi spent the first twelve
years of her career working as a general practioner and then became Assistant Professor in
infectious diseases at the University of Verona, Italy, focusing on HIV, TB, treatment of critically
ill patients, infection control and tropical medicine.
A worldwide perspective on infection control - prioritising settings with limited
resources
Prevention of healthcare-associated infection (HAI), the most frequent adverse event during
health-care delivery affecting hundreds of millions of patients around the world, is the target
of the Patient Safety Program “Clean Care is Safer Care”, launched by WHO in October 2005.
Dr Allegranzi’s research activities, conducted in the context of the programme, have focused
on hand hygiene, epidemiology of HAI worldwide, and HAI surveillance and infection control
implementation in developing countries. In particular, through her work Dr Allegranzi has
highlighted the burden of HAI in low-resource settings and has studied interventions to reduce
it. She leads a global campaign on hand hygiene, which currently includes more than 15 000
healthcare settings worldwide and a network of 48 national campaigns.
Allegranzi B, Bagheri Nejad S, Combescure C, Graafmans W, Attar H, Donaldson L, Pittet D (2011)
Burden of endemic healthcare-associated infection in developing countries: a systematic
review and meta-analysis. The Lancet 377:228-41.
Longtin Y, Sax H, Allegranzi B, Schneider F, Pittet D (2011) Hand Hygiene. Video in Clinical
Medicine. N Engl J Med 31;364.
Allegranzi B, Sax H, Bengaly L, Richet H, Minta DK, Chraiti MN, Sokona FM, Gayet-Ageron A,
Bonnabry P, Pittet D (2010) World Health Organization "Point G" Project Management
Committee. Successful implementation of the world health organization hand hygiene
improvement strategy in a referral hospital in Mali, Africa. Infect Control Hosp Epidemiol
31:133-41.
Pittet D, Allegranzi B (2008) Preventing infections acquired during health-care delivery. Lancet
372:1719-20.
Pittet D, Allegranzi B, Sax H, Dharan S, Pessoa-Silva CL, Donaldon L, Boyce JM (2006) WHO Global
Patient Safety Challenge, World Alliance for Patient Safety. Evidence-based model for hand
transmission during patient care and the role of improved practices. Lancet Infect Dis 6:641-52.
Contact: [email protected] , [email protected]
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Université de Genève • Faculté de médecine
Université de Genève • Faculté de médecine
77
Faculté de Médecine
Université de Genève
1, rue Michel Servet
1211 Genève 4
Faculty
www.unige.ch/medecine
Center of Excellence in Bacteriology (CEBUG)
www.cebug.ch
Maladies infectieuses (HUG)
maladiesinfectieuses.hug-ge.ch
Institute of Genetics and Genomics of Geneva, iGE3
www.ige3.unige.ch
Centre for Clinical Research
crc.hug-ge.ch
Genomic Research Laboratory
www.genomic.ch
Core Facilities
www.unige.ch/medecine/RECHERCHE/corefacilities_en.html
For citation of information within this booklet,
please contact the corresponding group leader,
or Patrick Linder
Thanks to all the contributors - including Cristiana Juge and Stéphane Couty
Project Manager: Patrick Linder
Graphic Design: René Aeberhard
Editing: Liz Hopkins
Coordination: Nicole Dana-Classen
Geneva, September 2012
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Université de Genève • Faculté de médecine