Call for Candidates to head a research group in the Institut Pasteur in Microbiology
3 years-postdoctoral positions available in the LabEx IBEID groups
Study of Chikungunya virus replication and entry into mammalian cells in the "Virus and Immunity" research unit directed by Olivier Schwartz at the Institut Pasteur
Chikungunya virus (CHIKV) is a re-emerging mosquito-borne alphavirus responsible for a recent, unexpectedly severe and long-lasting epidemic in the Indian Ocean region. Although many alphaviruses have been well characterized, the biology and pathogenesis of CHIKV are less understood. Very little is known about the cellular and molecular mechanisms of CHIKV entry and replication in mammalian cells. Our laboratory has completed, in collaboration with Institut Pasteur Korea, a genome-wide siRNA screen to identify cellular proteins involved in CHIKV replication.
The project is aimed at characterizing the role of selected proteins identified in this screen. The proteins will be silenced and/or expressed in relevant cells and the impact on viral replication and host/virus interplay will be studied, using state-of-the-art techniques in cellular and molecular biology, real-time imaging, virology and immunology.
Candidate requirements : Strong expertise in cellular biology, virology or immunology
To apply : Applicants should send their CV, a motivation letter and 3 references to Olivier Schwartz (firstname.lastname@example.org) Unité Virus et Immunité, Institut Pasteur, 28 rue du Dr Roux 75015 Paris.
Comparative genomic and phylogeographic analysis of two epidemic and multidrug resistant bacterial populations: Shigella dysenteriae type 1 (Shiga’s bacillus) and Salmonella Kentucky ST198 in the "Enteric Bacterial Pathogens" research unit directed by François-Xavier Weill at the Institut Pasteur
The LabEx IBEID seeks a Postdoctoral Scholar to perform comparative genomics on two epidemic and multidrug resistant bacterial populations: Shigella dysenteriae type 1 (Shiga’s bacillus) and Salmonella Kentucky ST198 from global collections (1915 to 2013).
The successful candidate will work under the supervision of Dr. François-Xavier Weill (http://www.pasteur.fr/ip/easysite/pasteur/en/research/labex/integrative-biology-of-emerging-infectious-diseases--ibeid-/principal-investigators/weill) and in collaboration with S. Le Hello, Institut Pasteur, S. Brisse, Institut Pasteur, K. Holt, University of Melbourne and N. Thomson, Wellcome Trust Sanger Institute.
The “Unité des Bactéries Pathogènes Entériques » (BPE Unit) is a Unit with both Research and Public Health activities. The research of the BPE Unit focuses on the biodiversity of enteric bacterial pathogens (population structures of Salmonella, Shiga toxin-producing E. coli, Shigella, and Vibrio, dynamics of particular populations, including those resistant to antibiotics) and on development of new molecular typing or subtyping methods for Public Health purposes.
Work on this project would include genetic and genomic analyses from a large number of strains (130-150 Shigella dysenteriae type 1 and 50-70 Salmonella Kentucky ST198) and 10-12 large multidrug resistant plasmids with a focus on bioinformatics using Illumina (strains) and 454 (plasmids) sequences, phylogenetic analyses, and microbiological lab work (omnilog phenotype microarray analyses, biofilm assays, development of strain-specific PCR or genotyping assays). The successful candidate will also be responsible for presenting and publishing the study results.
Candidate requirements : Qualified applicant must have a Ph.D. in bioinformatics, microbiology, computer science, or a related field with background and strong interest in microbial evolution. The ideal candidate will already have some experience working with large genomic data sets, experience with basic molecular biology techniques and oral and written communication skills as demonstrated by publications as first author in English language peer-reviewed journals and oral presentations at international meetings. Prior programming or scripting expertise is a plus.
To apply : Applicants should send their CV, a motivation letter and 3 references to François-Xavier Weill (email@example.com) Unité des Bactéries Pathogènes Entériques, Institut Pasteur, 28 rue du Dr Roux 75015 Paris
Importance of trypanosome motility during the early infection in the mammalian host in the "Trypanosome Cell Biology" research unit directed by Philippe Bastin at the Institut Pasteur
Human African Trypanosomiasis or sleeping sickness is a neglected tropical disease caused by the flagellated protist Trypanosoma brucei. Nagana is a similar disease in cattle due to closely related trypanosome species. The injection of these extra-cellular parasites by the bite of the tsetse fly induces a local inflammatory response. Trypanosomes then apparently transit via the lymphatic system before invading the bloodstream where they proliferate and cause the typical symptoms of the disease. However, very little is known about the early steps of infection, especially the mechanisms of trypanosome differentiation, proliferation and passage to the bloodstream.
The principal aim of this project is to establish the importance of the trypanosome flagellum that has been proposed to be a key virulence factor. In this context, the early steps of T. brucei development upon natural transmission of a fluorescent strain by a tsetse fly bite will be monitored using state-of-the-art intravital imaging technologies. Functional investigations with conditional knockout parasites will be performed to discover the role of flagellum motility in migration towards specific tissues and avoidance of host immune cells by using mutants deprived of flagellar motors. Overall, these studies will result in the first integrated view of the early steps of trypanosome infection and will be crucial to improve early diagnosis and treatment of this disease that is always fatal in the absence of treatment.
Candidate requirements : Candidates with at least a PhD in Biological Science, especially in Parasitology or Cell Biology are encouraged to postulate. Highly motivated and autonomous candidates are wanted. Skills in medical entomology and in vivo imaging would be appreciated.
To apply : Applicants should send their CV, a motivation letter and 3 references in the same pdf file to Brice Rotureau (firstname.lastname@example.org) Trypanosome Cell Biology Unit, Institut Pasteur, 25 rue du Dr Roux, 75015 Paris.
Pandemic Risk of Emerging Infectious Diseases in the " Epidemiology of Emerging Diseases" research unit directed by Arnaud Fontanet at the Institut Pasteur
Early, reliable detection of the pandemic potential of emerging infectious diseases is a problem of paramount interest. Despite considerable attention devoted to the control of new influenza viruses and coronaviruses, a systematic approach to using surveillance data for monitoring the evolving risk that an emerging pathogen will cause an epidemic is still missing. We propose to develop such a method to be applied to MERS-CoV, H7N9 or other emerging and pandemic-threatening pathogen.
Candidate requirements : (i) Ph.D. in applied mathematics, physics, engineering, computer science or a related quantitative field, (ii) solid mathematical background, (iii) excellent programming skills in low-level languages, (iv) excellent communication skills. Experience in mathematical biology is desirable.
To apply : Applicants should send their CV, a motivation letter, relevant reprints and 3 references (name, e-mail, address, phone, and fax no.) to Romulus Breban (email@example.com) Unité d’Epidémiologie des Maladies Emergentes, Institut Pasteur, 28 rue du Dr Roux 75015 Paris
Pathogenesis of enterovirus 71, a human emerging encephalitogenic virus in the "Biology of Infection" research unit directed by Marc Lecuit at the Institut Pasteur
Enterovirus 71 (EV71) is a human emerging virus closely related to poliovirus. EV71 has a worldwide distribution that is currently expending, and is a major cause of encephalitis associated with significant mortality in Asia. It causes a benign disease, hand, foot, and mouth disease (HFMD), and frequently lethal encephalitis, in particular in young children. In summer 2012, the emergence of EV71 in Cambodia led teams of Institut Pasteur of Phnom Penh, Shanghai and Paris to put together a task force. We have since worked on the identification of viral and host factors responsible of severe and fatal disease.
EV71 isolates from benign HFMD and from fatal encephalitis have been sequenced and mouse models for the disease have been developed. All isolates are closely related and differ from each other by a small number of nucleotides. We have characterized a genetically modified mouse model susceptible to EV71 infection in which a differential susceptibility to HFMD and encephalitis isolates is observed. We will use this model to map the viral determinants responsible for severe disease, and investigate their role in EV71 replication and cell and tissue tropisms. We have also shown that weaning mice of a genetically modified mouse strain are resistant to EV71 infection, in contrast to weaning wild-type mice of the same genetic background. We will investigate in this animal model the immune components that account for the increased severity of human EV71 infection in children. Finally, we will develop and characterize humanized transgenic mice expressing the two known human-specific EV71 receptors (SCARB-2 and PSGL-1) and will use them to study further viral and host factors implicated in human EV71 infection and pathophysiology.
This project will improve the understanding of the molecular bases of EV71 virulence and of the host factors involved in EV71-associated disease, in particular those implicated in disease severity in children. These findings will also constitute a basis from which develop antiviral strategies against EV71, and tackle a major public health threat for both developing and developed countries.
Candidate requirements : PhD, virology or cell biology. Applicants should ideally possess skills in virology, molecular biology and cell biology. Experiments on mice and mouse tissues would be appreciated. Applicants should be highly motivated and show an ability to work within a team.
To apply : Applicants should send their CV, a motivation letter and 3 references to Therese Couderc (firstname.lastname@example.org) Biology of Infection Unit, Institut Pasteur, Inserm 1117, 28 rue du Dr Roux 75015 Paris
Identification of tick molecules that contribute to tick-borne pathogens transmission in the "Biologie moléculaire et immunologie parasitaires et fongiques" research unit directed by Nadia Haddad at the National Veterinary School of Alfort.
Ticks, second only to mosquitoes, are the most important vectors of viral, bacterial and parasitic pathogens that affect humans and animals worldwide. Conventional control of tick-borne diseases is unsatisfactory, and new control strategies that are compatible with values of sustainable development and capable of addressing pathogen diversity and even anticipating pathogen emergence must be sought. One attractive solution is the development of vaccine strategies that target conserved components of ticks that play key roles in vector infestation or vector capacity. The primary rate-limiting step in this endeavour is identification of tick components that assure such functions and that represent protective antigenic targets. Indeed, and despite their importance, molecular interactions between ticks and the pathogens they transmit remain a “black box”.
The immediate goal of the project is to discover tick proteins that are implicated in pathogen transmission and to elucidate their function. The vaccine potential of these proteins will then be evaluated in different models. For this purpose, we have identified Ixodes ricinus proteins (by high throughput sequencing) that are highly expressed in tick salivary glands, and notably during bacterial infection. The transcriptome of the salivary gland of I. ricinus will be datamined to assign functional roles to tick proteins, and the implication of selected candidates in bacteria transmission will be evaluated by RNAi. The function of the most interesting genes will then be studied. Recombinant proteins corresponding to highly-expressed secreted proteins of functional interest will be produced, and their capacity to elicit an immune response tested in mice. Finally, the capacity of promising candidates to afford protection against ticks and TBP will be assessed in several challenge models of infection (mice, sheep, bovine). Ultimately, this project should provide 1) a better knowledge of molecular mechanisms underlying pathogen transmission by I. ricinus, the most important vector in Europe 2) immediate leads for better control of TBD and 3) knowledge to instruct development of next generation vaccines against TBD.
Candidate requirements : The successful candidate will have well-developed skills in bioinformatics and notably as regards prediction of protein function. Skills in molecular biology and murine immunology are also sought, but, if lacking, may be acquired in the host laboratory.
To apply : Applicants should send their CV, a motivation letter and 3 references to Sarah Bonnet (email@example.com) USC INRA Bartonella-tiques, UMR BIPAR ENVA-ANSES-UPEC, 23 Avenue du Général de Gaulle, 94706 Maisons-Alfort cedex, France.
Legionella pneumophila nucleomodulins: characterization and identification of their targets in the host in the " Biology of Intracellular Bacteria" research unit directed by Carmen Buchrieser at at the Institut Pasteur.
Understanding how pathogens induce chromatin modifications to affect their host is currently an emerging topic. Similar to viruses, bacteria may act in the nucleus by translocating genetic or epigenetic modulating factors, recently called “nucleomodulins”.
Using various tools we aim to identify and functionally characterize L. pneumophila proteins that target the host nucleus (nucleomodulins) and that are predicted to encode specific enzymatic activities. Recently we have identified and characterized the translocated effector RomA and have shown that RomA indeed targets the nucleus of the cell it infects and that it possesses specific methyltransferase activity against histone H3. We have now identified other Legionella effectors that encode a nuclear localization signal and are thus predicted to target the nucleus.
The aim of this project is to decipher the function of these newly identified, putative nuclear effectors and to characterize the host response induced by these Legionella nucleomodulins. Our long-term goal is to understand the global impact of nuclear modulations exerted by L. pneumophila during infection.
Candidate requirements : The successful candidate is expected to have a solid background in molecular biology and an expertise knowledge in cellular biology. Knowledge on host-pathogen interactions and eukaryotic signaling pathways involved in host-pathogen interactions is highly welcomed.
Requirements : PhD in relevant field - Appropriate experience in research and high motivation - Excellent scientific, organizational skills, reliable person - Initiative and independent work abilities - Excellent interpersonal and scientific communication skills, able to work in collaboration - Good English language skills for presentations and writing scientific papers
To apply : Applicants should send their CV, a motivation letter and 3 references to Carmen Buchrieser (firstname.lastname@example.org) Unité de Biologie des Bactéries intracellulaires, Institut Pasteur, 28 rue du Dr Roux 75015 Paris
Experimental evolution of arboviruses during natural transmission: identifying evolutionary trajectories and predicting emergence events in the "Viral Populations and Pathogenesis" research unit directed by Marco Vignuzzi at the Institut Pasteur.
Arboviruses (arthropod borne) make up a large list of clinically relevant human pathogens that obligately cycle between invertebrate (e.g., mosquitoes, ticks) and vertebrate hosts (e.g., birds, mammals). The virus must thus overcome a variety of physical and genetic barriers that both constrain and shape its evolution. The emergence of new adaptations that extend the virus' host range can lead to new epidemics, as was witness during the Indian Ocean islands outbreak of chikungunya virus in 2005/06. We have developed an approach coupling in vivo experimental evolution with deep sequence viral population analysis that has permitted us to identify these adaptive emergence events during a single replication cycle in vivo. The proposed work will mechanistically characterize new adaptive mutations identified in chikungunya virus, and experimentally identify similar adaptive events in other arboviruses.
Candidate requirements: Ph.D. in virology.
To apply :