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INSTITUT PASTEUR, DI, E. COEFFIER
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Title: Alternative immune strategies for the control of influenza infection
Supervisor: Valkenburg, Sophie, [email protected]
Institute within the Institut Pasteur International Network : HKU-Pasteur Research Pole, Hong
Kong SAR
Host laboratory: Valkenburg (HKU-Pasteur Research Pole, School of Public Health, The University
of Hong Kong)
More information:
http://www.hkupasteur.hku.hk/index.php/About_HKUPRP/postgraduate_studies
Rationale: Seasonal influenza vaccines are updated yearly due to antigenic drift, and outbreak
strains are not covered sufficiently by current available vaccines. Our group has a main interest in
the adaptive immune response to influenza during infection, by looking for universal immune
correlates of protection to develop broadly reactive vaccines. The research focus is heterologous T
and B cell immunity in mouse and human systems to determine the optimal protective immune
response. T cells do not neautrlaise influenza infection as they recoegnise infected cells, however
they are critical for viral clearance and can therefore impact viral transmission.
Project description: The duration and severity of influenza infection can be limited by established
T cell memory. In a human household transmission setting, a highly unique situation to Hong Kong
involving a network of field nurses, index and contact blood samples are taken to establish baseline
immunity and the correlation of T cell memory with influenza infection. Virus-specific T cells are
quantified and phenotypically characterized by in vitro stimulation and flow cytometry. Studies of
influenza epidemiology and clinical human samples in the context of naturally acquired infection are
limited to a handful of reports. Sample collection has been ongoing for seasonal infection in Hong
Kong, with an exciting opportunity awaiting PhD applicants.
Qualifications:
Academic and work experience : The applicant should hold a Masters degree or equivalent diploma
(completion of 5 years of higher education) in the area of Immunology or Virology.
Skills/competencies : The applicant should be proficient in basic laboratory techniques such as
tissue culture, molecular cloning and animal handling. Further skills specific to the project will be
trained.
Languages : English
Institute:
Unit/Laboratory/Research Group : The HKU-Pasteur research pole at the University of Hong Kong is
a world leading influenza laboratory, with combined access to animal surveillance, BSL3, clinical
samples and fundamental influenza virology research.
Group Leader : Dr Valkenburg is an early career researcher, originally from The University of
Melbourne, Australia and now well established at the University of Hong Kong. Her workgroup aims to
address correlates of universal immunity towards influenza. She has published in top journals and
holds independent grants.
Funding opportunities : Funding covers living and insurance expenses in line with the scales of
the University of Hong Kong studentships
(http://www.gradsch.hku.hk/gradsch/prospective-students/scholarship-funding-and-fees)
One return fare between the home country and Hong Kong is also funded.
INSTITUT PASTEUR, DI, E. COEFFIER
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Title: Characterization of the non-H. pylori flora among patients at different histological
stages of infection, from gastritis to preneoplastic lesions and gastric cancer.
Supervisor: Breurec, Sebastien, [email protected]
Institute within the Institut Pasteur International Network : Institut Pasteur de la Guadeloupe,
Les Abymes, Guadeloupe, France
Host laboratory: Unité Environnement et Santé
More information: http://www.pasteur-guadeloupe.fr
Rationale: Persistent colonization of the gastric mucosa by Helicobacter pylori is associated with
pathologies ranging from gastritis, peptic ulcer disease to gastric cancer (GC) that accounts for
800,000 deaths in the world every year. H. pylori infection is recognized as the main risk factor for
distal gastric cancer, although just a fraction of infected patients (<3%) ever develop GC. H. pylori is
not alone in the stomach. Gastric microbiota through the inability to contain deleterious gut
microbes (barrier function), through defective host immunoregulation, or both, is suspected to
promote the disease and to determine the progression of the inflammation to preneoplastic stages.
Thus, a ‘protective’ or a ‘deleterious’ gastric microbiota, if existing, could participate to difference of
cancer risk.
Project description: The aim of our project is to characterize the non-H.pylori flora among
patients at different histological stages of infection, from gastritis to preneoplastic lesions and GC.
We will collect information on sex, age, diet, obesity and lifestyle. One hundred gastric biopsies will
be selected. For each selected patient, we will attempt bacteria cultivation from one biopsy. If H.
pylori is obtained in culture, strains will be characterized by MLST, and the classic virulence factors
will be systematically searched. Our experimental strategy will use high-throughput sequencing
technologies, which have increased the capability and scope of the study of complex microbiomes.
The expected observation of shifts in the gastric microbiota between histological stages will have
potential applications both for the understanding of the progression of the disease. A project based
on the same methodology including two centres in Africa where the infection prevalence can reach
80% (Senegal, Algeria) will be submitted in 2016 for ACIP funding.
Qualifications: Academic and work experience : The PhD student should have completed a Master
degree or equivalent within the field of computational biology or related fields.
Skills/competencies : Techniques required for this research project include NGS technologies.
Familiarity with this type of data and methods for analysis as well as the relevant statistics will be
an advantage.
Languages : French, English
Institute: Environmental-Health unit: Created in 2010, this unit is composed of five researchers,
one post-doctoral researchers, 3 PhDs and 3 technicians. The research topics are oriented on
relation of health with the environment (medical entomology, environmental pathogens, antibiotic
resistance). A new topic is being developed concerning the relation between microbiome and
various environmental conditions and the proposed project is part of this program.
Group Leader : Dr. A. Talarmin is author of 85 publications with expertise in Microbiology and
Environmental Health.
Funding opportunities : European Fund for Economic and Regional Development
INSTITUT PASTEUR, DI, E. COEFFIER
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Title: Transcriptomic and proteomic analysis of novel virulence factors in the human fungal
pathogen Cryptococcus neoformans
Supervisor: Chen Changbin, [email protected]
Institute within the Institut Pasteur International Network : Institut Pasteur of Shanghai,
Shanghai, China
Host laboratory: Unit of Pathogenic Fungal Infection & Host Immunity
More information:
http://english.shanghaipasteur.cas.cn/rh/ru/Pathogenic_fungal/201212/t20121211_96724.html
Rationale: The doctoral program is rooted in host-fungal interactions and explores mechanisms
involved in pathogenic fungal infection and host anti-fungal immune responses. The program
•
studies host-pathogen interactions from multiple scientific perspectives and
enhances the capacity to teach hypothesis driven scientific investigation; and
•
provides students with a broadly based educational experience and teaches them to
effectively communicate their particular research experiences to a general audience.
Project description: Our previous genetic screen for C. neoformans mutants with compromised
growth in the mammalian host yielded 11 previously-unstudied and predicted to be novel
transcriptional factors and 10 encode proteins whose functions are unknown.
The goal of this proposal is to develop powerful experimental tools for studying novel virulenceassociated transcriptomes and proteomes in the genetically tractable haploid human pathogenic
fungus Cryptococcus neoformans.
Specific aims:
1. Determine the fungal transcription programs required for virulence during infection
2. Purify and identify interacting partners of protein with unknown function
3.
Characterize the interacting partners of each unknown protein and find clues to function
Qualifications:
Academic and work experience : Students with interdisciplinary training in microbiology are in
increasing demand
Skills/competencies : Basic skills in molecular biology and biochemistry
Languages : Fluent in English Communication
Institute:
Unit/Laboratory/Research Group : Unit of Pathogenic Fungal Infection & Host Immunity
Group Leader : Changbin Chen, Ph.D.
Funding opportunities : NSFC program, The 100 talent Program from CAS
INSTITUT PASTEUR, DI, E. COEFFIER
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Title: Host factors determining Dengue, Zika or Chikungunya viruses infections
Supervisor: Dimitri LAVILLETTE; [email protected]
Institute within the Institut Pasteur International Network : Institut Pasteur Shanghai, Shanghai,
China
Host laboratory: Arbovirus interspecies transmission and therapeutics research
More
information:
http://english.shanghaipasteur.cas.cn/rh/ru/Dimitrizu_153831/201504/t20150403_146093.html
Rationale: 8-10 lines about the context
During the past 20 years, there has been a dramatic resurgence or emergence of epidemic virus
diseases affecting both humans and domestic animals. Most of these diseases are caused by
arthropod-borne viruses (arboviruses) which are transmitted from insects to hosts following blood
meals. Most of these arboviruses are increasing their geographical area following the extension of
their insect vectors. These arboviruses include, among others, Zika flavivirus that is hitting Brazil
recently and Chikungunya alphavirus that enter the Caribbean and American continent at the end of
2013. However so far there is no specific treatment against arboviruses and only some have vaccine
approved for human use.
Project description: 10-12 lines about the project
By studying both infections in mammals and insects, in vitro and in vivo, our global project wants to
unveil the viral and/or host factors responsible for pathogenicity or resistance. Using different
Alphavirus models, we want to explore: i) the host factors involved in entry, interspecies
transmission and host susceptibility; and ii) the role of cell response in virus replication, in vivo
spreading and difference of cytopathogenicity. These understanding will help to develop new
strategies to fight these public health and veterinary threats. We are using different arbovirus models
like Dengue, Zika and Chikungunya viruses.
Qualifications:
Academic and work experience : Master in biology, virology
Skills/competencies : cell culture, molecular biology, biochemistry, Flow cytometry
Languages : Good English, French or Chinese is a plus
Institute:
Unit/Laboratory/Research Group : Our team was created in 2014 and is now composed of 8
members. We have 3 international PhD students, some being involved in a PhD joined program
between France and China. Our team is located in a new building on the SIBS campus and it has all
modern equipment and cutting edge technologies.
Group Leader : Dimitri LAVILLETTE is a French researcher specialist of virus entry, entry
inhibitors, vaccine strategies. He has a long experience in Retroviruses, Hepatitis C virus and since 2
years, he is developing projects on Arboviruses.
Funding opportunities : 100 Talent of CAS, 1000 Talent of Shanghai municipality.
INSTITUT PASTEUR, DI, E. COEFFIER
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Title: Modulation of host factors on HIV-1 latency
Supervisor: WANG, Jian-Hua, [email protected]
Institute within the Institut Pasteur International Network : Institute Pasteur of Shanghai, China
Host laboratory: Unit of Viral Immuology
More information:
http://english.shanghaipasteur.cas.cn/rh/ru/Immunology/201003/t20100324_52150.html
Rationale: 8-10 lines about the context
Persistence of HIV-1 infection due to viral latency is the major barrier to eradication of AIDS.
Although highly active antiretroviral therapy (HAART) effectively reduces HIV-1 replication and viral
load below the limit of detection in most infected individuals, a reservoir of infected cells persists.
The limitation of long-term HAART and the presence of HIV-1 reservoir necessitate the development
of alternative therapeutic strategies for HIV-1 cure. Basic research on the cellular mechanisms
regulating HIV-1 latency would generate new strategies to potentially facilitate a functional cure for
AIDS.
Project description: 10-12 lines about the project
HIV-1 latency is characterized by a reversible silencing of viral promoter long terminal repeat
(LTR)-driven transcription of an integrated provirus. The post-translation histone epigenetic
modifications is one of the cellular factors accounting for repressive chromosome, and the lack of
sufficient transcription factors or existing the repressive factors have been described to contribute
to the transcriptional silencing of HIV-1 latency. By using HIV-1 latently infected cells and the resting
CD4+ T cells isolated from HAART-treated patients, the project is to identify host factors that
modulating HIV-1 replication and latency.
Qualifications:
Academic and work experience: Virology, Immunology, or Cell biology
Skills/competencies: Molecular biology.
Languages: English, or Chinese
Institute:
Unit/Laboratory/Research Group: Unit of Viral Immunology, Institute Pasteur of Shanghai, Chinese
Academy of Sciences, Shanghai, China.
Group Leader: Jian-Hua Wang, PhD
Funding opportunities : NSFC-NIH joint grant, NSFC grants.
INSTITUT PASTEUR, DI, E. COEFFIER
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Title: The role of CD95 nonapoptotic function in gammaherpesvirus-associated
lymphomagenesis
Supervisor: Liang, Xiaozhen, [email protected]
Institute within the Institut Pasteur International Network: Institut Pasteur of Shanghai,
Shanghai, China
Host laboratory: Virus-associated lymphoma Unit
More information:
Rationale: While CD95 is an apoptosis-inducing receptor and emerges as a potential anticancer
therapy target, mounting evidences indicate nonapoptotic function of CD95 for promoting
tumorigenesis. Gammaherpesviral infection is tightly associated with lymphoproliferative diseases
including B cell lymphomas. The non-apoptotic function of CD95 in gammaherpesvirus-associated
lymphomas is largely unknown. We have recently shown that CD95 stimulation inhibited B cell
receptor (BCR)-mediated gammaherpesviral reactivation of apoptosis-resistant lymphoma cells
without influencing BCR signaling, indicating that independent of its apoptotic activity, CD95
signaling activity plays an important role in blocking viral lytic replication in apoptosis-resistant,
gammaherpesvirus-associated lymphoma B cells.
Project description: The current project aims to investigate the underlying molecular mechanisms
of how CD95-mediated nonapoptotic signaling regulates gammaherpesviral reactivation in those
apoptosis-resistant lymphoma cells and lymphomagenesis in vivo. We will also investigate whether
CD95 nonapoptotic signaling has important roles in viral infection which has never been studied
previously. This project will collaborate with Dr. Patrick Legembre in INSERM , France who is expert
in CD95 study.
Qualifications:
Academic and work experience: microbiology, cell biology
Skills/competencies : Basic molecular, cellular and biochemistry technique, cell culture
Languages : English
Institute:
Unit/Laboratory/Research Group : Virus-associated Lymphoma
Group Leader : Xiaozhen Liang
Funding opportunities : NCSF, “100 talent” program
INSTITUT PASTEUR, DI, E. COEFFIER
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Title: Study of innate immune responses against hepatitis C virus infection
Supervisor: ZHONG, Jin, [email protected]
Institute within the Institut Pasteur International Network : Institut Pasteur of Shanghai,
Shanghai, China
Host laboratory: Unit of Viral Hepatitis
More information:
http://english.shanghaipasteur.cas.cn/rh/ru/VIRAL/201003/t20100324_52132.html
Rationale:
Hepatitis C virus (HCV) causes acute and chronic hepatitis and liver cancer, and becomes a major
worldwide human health problem. It currently infects more than 170 million people in the world and
38 million people in China. Great progress has been made in the treatment of chronic hepatitis c in
recent years. However, due to the lack of HCV vaccine, HCV infection is still threatening public health.
We are interested in studying the innate immune responses against HCV infection, focusing on how
the virus induces innate immunity, how innate immunity suppresses HCV infection, and how HCV
evades host innate immunity. Hopefully by further understanding how the virus prevails during the
infection and how the host limits the viral infection, we will be able to find a better way to prevent
and treat HCV infection.
Project description:
The innate immune response against HCV infection has been extensively studied. HCV’s RNA genome
contains a Pathogen-Associated Molecular Pattern (PAMP) in its 3’ untranslated region (3’UTR),
which, after being delivered into hepatocytes by transfection, can be recognized by host Pattern
Recognition Receptor (PRR) RIG-I to activate interferon production via MAVS/VISA, an important
adaptor protein in the interferon signaling pathway. However, it is difficult to test this notion in the
context of HCV infection, because the virus-encoded NS3/4A protease suppresses this signaling
pathway by cleaving MAVS/VISA. Recently, we developed a hepatic cell line in which MAVS/VISA is
no longer cleaved by the NS3/4A protease such that the HCV infected cells can produce interferon.
Using this cell line, we found that HCV infection induced interferon signaling is mainly mediated by
MDA5. We will further explore molecular mechanism for how HCV infection activates the interferon
signaling pathway.
INSTITUT PASTEUR, DI, E. COEFFIER
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Title: Function of NLRP3 inflammasome in the skin upon Leishmania challenge
Supervisor: Meng, Guangxun, [email protected]
Institute within the Institut Pasteur International Network : IPS, Shanghai, China
Host laboratory: Unit of Innate Immunity, IP Shanghai
More information:
http://english.shanghaipasteur.cas.cn/rh/ru/InnateImmunity/201003/t20100324_52153.html
Rationale:
An international mixed unit has been organized based on collaborative actions between three teams
at IP Paris (G. Spaeth), IP Shanghai (G. Meng) and IP Korea (J.H. No). My unit in Shanghai will explore
the function of NLRP3 inflammasome in the skin upon Leishmania infection, which is the causative
parasite for Leishmaniasis. Thus, a PhD position is open for this project.
Project description:
Various genetically modified mice are available in the lab and the Leishmania infection system has
been well established. The qualified candidate needs to have a strong background in mice experiment,
well trained in immunology studies, motivated to dissect mechanisms in animal studies in
Leishmania skin infection studies. A high impact publication is expected in the immunology field
upon finishing of this study.
INSTITUT PASTEUR, DI, E. COEFFIER
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Title: Identification and development of novel curative Hepatitis B virus drugs
Supervisor: Dr Ezzikouri Sayeh, [email protected]
Institute within the Institut Pasteur International Network : Institut Pasteur, Paris, France/
Institut Pasteur Korea
Host laboratory: Centre De Bioinformatique, Biostatistique Et Biologie Intégrative/Bioinformatique
Structruale (Bis)/Prof Michael Nilges and Dr Arnaud Blondel. Institut Pasteur Korea, Hepatitis
Research Laboratory/ Dr Marc Windisch
More
information:
https://research.pasteur.fr/fr/team/structural-bioinformatics/;
http://www.ip-korea.org/RDP/HRL.php
Rationale: Hepatitis B virus (HBV) is a major cause of liver disease and hepatocellular carcinoma.
Chronic hepatitis B is currently managed with either nucleoside/nucleotide-based or interferonbased therapies. Most drugs of this class are reported to have viral resistance with breakthrough and
fail to cure HBV infection. Consequently, there is an urgent unmet medical need for the development
of novel inhibitors, which might be used as an alternative or to in combination with already existing
therapies. The recent progress in hepatitis C virus (HCV) therapy with novel direct-acting antivirals
allowing to cure chronic HCV infection has created expectations to cure HBV infection. To address
this needs, we intend to evaluate small molecule compound libraries to identify and characterize
novel HBV interventions.
Project description: In 2012 with the discovery of sodium taurocholate cotransporting polypeptide
(NTCP), a crucial entry receptor, it became possible to study yet unexplored steps in the HBV life
cycle. Moreover, targeting the HBV capsid and preventing the core protein from naturally forming
the capsid has become a new therapeutic strategy for developing effective anti-HBV drugs. By
performing computer-assisted virtual screening against S-NTCP and capsid structures, we will
identify a potential targeting compounds. In addition, using NTCP overexpressing HepG2 cells, we
are planning to optimize and validate an image based screening assay enabling quantification of HBV
infectious activity. Upon miniaturization and adaption to 384-well plate format, this assay should be
amenable to high throughput campaigns screening (HTS) of 10,000 small molecules targeting HBV
entry via NTCP. We will plan also to screen a plausible hits affecting capsid assembly identified
thought virtual screening using HepG2.2.15 cell line.
All this steps are predestinated targets for small molecules by chemoinformatics tools and after in
depth characterization of inhibitors by classical virological methods the generated knowledge will
shed light on the poorly understood HBV life cycle and potentially provide new opportunities for
further drug development.
Qualifications: Academic and work experience: Sayeh Ezzikouri is a Research scientist, in Virology
Unit, Viral Hepatitis Laboratory at Institut Pasteur du Maroc. Dr Ezzikouri got a PhD from Chouaib
doukkali University, Morocco in 2008. He spent 2 years as assistant professor in Kagoshima
University, Japan and published in the area of hepatitis B, C and liver cancer more than 37 paper
especially in epidemiology, virology, animal models, new drugs and genetic susceptibility to hepatitis
infections and disease progression to liver cancer.
Skills/competencies: Cell culture; Molecular Biology & Genetics; Virology; Cell biology; animal model;
Biostatistics
Languages :Arabic, French, English
Institute: Institut Pasteur du Maroc
Unit/Laboratory/Research Group : Virology Unit, Viral Hepatitis Laboratory
Group Leader : Soumaya Benjelloun
Funding opportunities : PTR2016
INSTITUT PASTEUR, DI, E. COEFFIER
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Title: Identification of novel therapeutic targets and anti-cancer drugs from snake and
scorpion venom using image-based phenomic screening
Supervisor: Oukkache, Naoual, [email protected]
Institute within the Institut Pasteur International Network:
1- Institut Pasteur Korea (IP-K), Seoul, Korea
Host laboratory: Cancer Biology research laboratory
More information: http://www.ip-korea.org
2- Institut Pasteur de Montevideo, Uruguay
Host laboratory: IIBCE-Instituto Pasteur de Montevideo
More information: www.pasteur.edu.uy
Rationale: Cancer is the first cause of mortality worldwide. The World Health Organization has
estimated 84 million deaths between 2005 to 2015. The cancer still causes one in five deaths and it’s
estimated that it will reach the 150 million mark before 2020. The challenge of anti-cancer therapies
is to develop potent and non-toxic anti-cancer agents with a double action to block multiplication of
cancer cells but impede the formation the vessels that feed the tumor. The anticancer effects of
scorpion and snakes venoms have been reported for several scorpion and snakes species and in
different cancer types. In Morocco, despite that the venom of snakes and scorpions is an enormous
source of peptide, toxins and enzymes that have a great of therapeutic interest; so far they haven’t
been explored in the search for their biological activities.
Project description: Pasteur Institute of Morocco previously identified and characterized several
molecules from snake and scorpion venoms. In particular, these molecules described in other
venoms as the inhibitor of cancer cells.
This project is part of efforts to identify of novel therapeutic targets and anti-cancer drugs from
snake and scorpion venom using image-based phenomic screening (Technology of IP-K). We
propose to apply this technology to identify the new anti-cancer molecules from snake and scorpion
venoms. These molecules will be screened in different tumor cell lines representing lung cancer,
liver cancer, gastric cancer and breast cancer. IP-K developed a state-of-the art phenotypic HCS
assay to estimate proliferation, migration, and apoptosis of tumor cells. The phenotypic HCS assay
system supports the identification of compounds from scorpion or snake venoms for inhibition of
tumorgenesis. Once we identify compounds of interest, we can further apply IP-K screening tools to
identify potential targets of compounds.
Qualifications:
Academic and work experience:
phD in Biochemistry; Scorpion and Snake venoms
Skills/competencies: Biochemistry; Immunotherapy; Biotechnology; Proteomics and toxicity
analysis
Languages: Arab; French; English and Portuguese
Institute:
Research/Biochemistry/ Venoms and toxins – Pasteur Institute of Morocco
Group Leader: Dr Naoual Oukkache
INSTITUT PASTEUR, DI, E. COEFFIER
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