Offres de stages postdoctoraux à l'Institut Pasteur

22/05/2012 - The role of intracellular TLR9 trafficking and signaling in an inflammation model

  • Description
A two year position funded by the French National Research Agency  (ANR) is available in the Unit Cytokines & Inflammation at Institut Pasteur Paris, starting june 2012. The project is to study the role of intracellular TLR9 trafficking and signaling in an inflammation model with Dr Noelle DOYEN. Studies will focus on the analysis of the inflammatory responses in TLR9, Asparagine endopeptidase (AEP) and Cathepsin B, L, S, or K (Cat B,L,S,or K) deficient mice in the course of infection by Leishmania major. The role of these proteases in endosomal TLR stimulation has been previously shown. Their role in the trafficking of TLR and their relevance for the onset of innate and adaptive immune responses in L. major infection will be now investigated.
 
TLR9-deficient mice (TLR9-/-) are more susceptible to infection with L. major than wild type (WT) C57BL/6 mice. TLR9-/-mice resolve their lesions and control parasites growth with a much lower efficiency than WT.  Preliminary data suggest that, in vitro, DCs lacking AEP activity infected by L. major are unable to respond, due to the impaired processing of TLR9. TLR9 processing is impaired in macrophages isolated from Catl deficient mice but not in macrophages lacking AEP. We will compare the susceptibility of AEP-/-, TLR9-/- and different Cat-/- mice following inoculation by L. major promastigotes. 
 
In order to establish the impact of TLR9 signaling in DCs and macrophages, we will investigate the development of cutaneous lesion and parasites burden after infection, until the healing of the lesions. We will analyse the recruitment of DCs, macrophages, neutrophils and T lymphocytes as well as proinflammatory cytokines and chemokines expression at the site of infection and in the draining lymph nodes. The orientation of the T cell response by measuring the expression of IFN-and IL-4 in T lymphocytes during the course of infection in TLR9, AEP, and CatL deficient mice will be also compared. 
Purified vertebrate DNA is unable to stimulate TLR9 but it has already been shown that the DNA from some protozoan parasites activate macrophages. Purified L. major DNA also induces the activation of DCs but the mechanism of such activation remains unsolved. Our plans are to determine the origin of the specific TLR9 dependent  activation caused by L. major DNA in DCs and in macrophages. 
 
This project is part of an ANR grant investigated by B. Manoury (Necker hospital U1013, coordinator  of  the project) N. Doyen and L. Touqui, (from the Department of Infection and Epidemiology of Insitut Pasteur, unit Cytokines & Inflammation and unit Innate host defense and Inflammation U 874), respectively. 
 
This project will give important new insights in the field of leishmania research. Annual incidence of cutaneous leishmaniasis is estimated at 1-1.5 million cases worldwide. Overall prevalence of the disease is 12 million people and the population at risk is 350 million people. 
 
The Institut Pasteur, located in the heart of Paris, provides an international and dynamic research environment with state-of-the art imaging and animal colonies facilities.
 
  • Qualification
The applicant should have obtained his/her PhD.
The candidate should have strong experience in cell biology, molecular biology , cellular imaging and conceptual training in immunology and parasitology. The working language is English; strong written and oral communication skills are required.
 
Funding : CNRS postdoc salary scale (2 years) .
 
  • Contatc :
Please send full CV including research interests and 2 or 3 references with contact information to : 
Dr Noëlle DOYEN
Group E3 In Unit of Cytokines and Inflammation
28 rue du Docteur Roux
75724 PARIS Cedex 15
 

04/05/2012 - Post Doc position in Molecular and cellular biology of Lyssavirus infection

  • Description
The capacity of zoonotic RNA viruses to emerge and re-emerge as major agents of human diseases can appear almost limitless. Although current intervention strategies have demonstrated some success, rapid, innovative and effective solutions are needed to reduce the impact of new strains as they emerge. A FP7 program called: Preparedness, Prediction and Prevention of Emerging Zoonotic Viruses with Pandemic Potential using Multidisciplinary Approaches (PREDEMICS: http://predemics.biomedtrain.eu) is providing a platform for global analysis of the factors involved in crossing of the host species barrier and of the causal mechanisms leading to the emergence, maintenance and enzootic expansion of lyssaviruses, the agents of rabies, in animals and finally transmission to humans. Advanced knowledge on fundamental aspects of the viral reproductive and dissemination processes and on virus-host interactions will provide new potential approaches for interventions. Within this program, a three years post doctoral position is available immediately in the Unit Lyssavirus dynamics and host adaptation at the Institut Pasteur in Paris (head: Hervé Bourhy).
Through the development and use of new molecular models and inference tools, you will contribute to the analysis of the genetic diversity and evolutionary dynamics of lyssaviruses within its various hosts. You will focus on the identification of viral genetic determinants involved in cross-species transmission from the dog to other carnivores. You will also investigate the pathogenesis of recombinant viruses obtained by reverse genetics exhibiting the different potential genetic signatures identified. Furthermore, using analyses in vitro and in vivo, youwill characterize and evaluate viral and cellular factors that influence innate immunity and potential host switching.
 
  • Qualification
The position is ideally suited for highly motivated and enthusiastic applicants with a PhD and a strong background in virology, molecular and cellular biology with an established publication record. Strong written and oral communications skills in english are required.
 
  • Additional Information :
Start date : immediately (duration 3 years)
Gross salary: around 2,700 Euros per month
Location : Paris, France
Applicants should send their CV, a list of publication, a summary of their previous research activities (≤3 pages), a personnal statement and the names of three referees to the secretary of the unit, E-Mail : edith.martin@pasteur.fr and use the following reference in the subject of the message: PostDoc PREDEMICS.
Dead line for submission: May, 28th 2012

09/02/2012 - Postdoctoral position in the Laboratory of Trypanosoma Infectious
ProcessesKey words

A postdoctoral fellowship is available to join the laboratory of Trypanosoma Infectious Process at the Institut Pasteur in Paris, France, to work on a project funded by the Foundation for Medical Research (FRM) *. To apply for this position, candidates must have a Ph.D. in biomedical Sciences and a scientific experience in the field of host-microorganism interaction (preferably with parasites) using /in vivo/ immunobiological approaches. Proven skills in cellular biology, particularly with in vitro models of infection, are essential prerequisites for the further optimization and preclinical developmentof chemical compounds. Experience in biochemistry will be appreciated. Proficiency in French and English is required.

Interested candidates should submit their Curriculum vitae and two reference letters to Paola Minoprio, pmm@pasteur.fr, dead-line April 15th 2012.

*FRM Project : «Optimization of proline racemase TcPRAC inhibitors to treat Chagas' disease» ; 12 months postdoctoral fellowship,**from September 1st 2012 - August 31th 2013.

20/12/2011 - Two postdoctoral positions in the Nuclear Organisation & Oncogenesis Laboratory

Key words

Epigenetics, chromatin, post-translational modifications, sumoylation, cellular senescence, inflammation, cancer

Description

Two post-doctoral positions are available in the Nuclear Organisation and Oncogenesis Laboratory at the Institut Pasteur to work on the role of sumoylation in chromatin structure and function in normal and tumor cells. The ubiquitin-like modification by SUMO is emerging as an essential regulatory mechanism of protein function which is involved in most challenges faced by eukaryotic cells. Gene expression appears to be particularly regulated by sumoylation as many known SUMO substrates are transcription factors and cofactors. Moreover, key chromatin proteins, including the core histones, figure among the SUMO targets. The emerging paradigm for the proposed work is that sumoylation controls multiple aspects of chromatin structure and that sumoylated proteins are principal and instructive components of a dynamic chromatin scaffold that can respond to external cues. In this context, the project aims to define the role of sumoylation in chromatin biology, its plasticity upon oncogenic and inflammatory stress and to analyze the possible impact of dysregulating this pathway in cancer. 

Experience and skills of the candidate

Candidates should have proven research skills in epigenetics, chromatin biology and protein biochemistry. Experience in cancer biology and/or computational biology will be a plus. The appointments will be financed by an ERC advanced grant for 3-4 years. The starting dates will be decided in agreement with the selected candidates.  

Contact

Applications in the form of a cover letter with a brief statement of research experience, technical expertise and interests, a CV, a list of publications and contact details of two referees, should be sent to:
Anne Dejean
Nuclear organization and Oncogenesis Lab/INSERM U993
Institut Pasteur, Paris
Tel. 33 / 1 45 68 88 86
Fax 33 / 1 45 68 89 43
adejean@pasteur.fr


24/11/2011 - Two postdoctoral positions in the Lymphocyte Development & Oncogenesis Laboratory

Two postdoctoral positions are available immediately in the Lymphocyte Development & Oncogenesis Laboratory in the Immunology Department at the Institut Pasteur Paris to work on ambitious projects aiming to decipher the mechanisms and pathways leading to genome instability and tumor development in B and T lymphocytes.

Research Keywords:

Cancer, Immunology, Mouse models, Lymphocyte development, Genomics, Genome integrity, DNA repair, DNA damage

Projects outline:

Lymphoid cancers are among the most common human malignancies and characteristically harbor genomic aberrations. We are interested in developing experimental approaches that would provide an understanding of how and which genomic aberrations underlie tumor genesis. It has become apparent that the generation of DNA double strand breaks (DSB) during the programmed process of antigen receptor diversification, including RAG1/2 protein-generated DNA breaks during V(D)J recombination, are key common intermediates in the appearance of lymphoid neoplasm. We have created a series of mouse models carrying aberrant V(D)J recombination leading to the rapid development of lymphoid tumors, reminiscent of human malignancies. In this project, we aim to elucidate the molecular mechanisms, the genomic lesions and the oncogenic pathways underlying B and T cell cancers using a combination of genetically engineered mouse models computational technologies

Candidate requirements:

Candidates should be highly motivated by cancer biology, cancer genomics and genome integrity research fields and be willing to take on intellectual, scientific and technical challenges. The applicant should have a record of delivering high quality research and strong experience in the subjects of cancer, immunology, genomics, mouse models, or lymphoma and leukemia. Experience in transcriptomic and genomic analysis and/or computational biology would be desirable. Preference will be given to candidates with less than two years of experience after his/her Ph.D.

To apply:

 Applicants should send a cover letter with a brief statement of research experience, technical expertise and interests, a C.V., a list of publications and three references to Ludovic Deriano (ludovic.deriano@pasteur.fr)


26/10/2011 - Two postdoctoral positions are available in the Innate Immunity Unit

Two postdoctoral positions are available in the Innate Immunity Unit (http://www.pasteur.fr/recherche/UPDATE) in the Immunology Department at the Institut Pasteur starting January 2012 utilizing 'humanized' mice harboring human lympho-hematopoietic systems for projets relating to preclinical studies of human immunology. HIS mouse models provide an opportunity to decipher the molecular mechanisms controlling human lymphocyte development and function. Progress in this area has been rapid (Manz and Di Santo, Nat Immunol 2009) and research and clinical applications for HIS mice are attracting industrial partners at an unprecendented rate. Three-year positions are funded through the ANR (program RPIB, project 'Im_HIS').

The Innate Immunity Unit has a long-standing interest in the development of xenograft mouse models for the analysis of immune responses to pathogens and cancer. Thanks to a previous award from the Bill and Melinda Gates Foundation (Grand Challenges in Global Health), a series of innovative immunodeficient recipient strain for HIS mouse generation were developed (Huntington et al, JEM 2009; Huntington et al PNAS 2011; Legrand et al PNAS 2011). The successful applicant will use these new HIS models in order to model and study the pathogenesis of human infectious diseases, using state-of-art instruments and in vivo approaches available in the lab and across the institute.

QUALIFICATIONS: Interested candidates must be completing or should have obtained a Ph.D. or M.D. degree with background in Immunology, Molecular Biology, Cell Biology, Physiology or a related discipline. The applicant should have record of delivering high-quality research using immunology, molecular biology, and/or animal models. Experience in transcriptional analysis, multi-parameter flow cytometry and/or mouse models are highly desirable.

SALARY/BENEFITS: These positions are fully supported by the ANR and successful candidates will be offered competitive stipend/salary and benefits commensurate with experience and accomplishments.

TO APPLY: E-mail your CV and at least 3 references to James Di Santo (james.di-santo@pasteur.fr) by November 15, 2011.

 

26/10/2011 - Hypermutation of DNA by APOBEC3 host cell mutators in peritumoral tissue

Prof. Simon Wain-Hobson

Molecular Retrovirology Unit

Institut Pasteur, Paris

 

A 3 year post-doc doctoral position is available. The project is financed in the context of a Medicen-funded project TelVac and involves two companies, and three basic research labs. The post-doctoral work will be carried out in a research lab at Institut Pasteur.

Hypermutation follows from extensive deamination of cytidine residues in DNA and was initially thought to be confined to viral genomes (Vartanian et al. Science 320, 230 (2008); Vartanian et al. PLoS Pathogens 6, e1000928 (2010)). More recently we have shown that mitochondrial can be dited by several APOBEC3 enzymes, and more importantly, nuclear DNA can be hypermutated (Suspène et al. 108, 4858 (2011)). And of course, somatic mutation brings us to cancer. This ties in well with the large number of GC->AT mutations that characterise cancer genomes. This is now the major research interest of the lab.

The project seeks to define the APOBEC3 transcriptome as well as those of related genes and interactors in lung cancer and peritumoral tissue. Considerable tissue culture work on the promoter and interactors will be performed to consolidate and explore the in vivo findings. A good knowledge of molecular and cellular biology is useful.


11/08/2011 - Mechanisms of adaptation of pandemic A/H1N1v (2009) influenza virus to humans / étude de mécanismes d’adaptation du virus grippal pandémique A/H1N1v (2009) à l’homme

As part of a research program that involves several laboratories of the Ile-de-France Region, a post-doctoral position is available for a two-year period in the research group of Dr. Nicolas Escriou (Viral Genomics and Vaccination Unit, Institut Pasteur, Paris, France). The program aims at studying the mechanisms of adaptation of pandemic A/H1N1v (2009) influenza virus to humans. Notably, the program will explore the contribution of innate immunity responses and identify viral determinants involved in this process.

The post-doctoral fellow will be responsible for the development and implementation of the guinea pig animal model, and will contribute to the development of the viral reverse genetics system. He/She will perform transcriptome analyses in infected cells and animals. This program involves experiments in BSL2 and BSL3+ research facilities.

The research interests of the Viral Genomics and Vaccination unit, headed by Dr Frédéric Tangy at the Institut Pasteur in Paris, are focused on the study of functional virus-host interactions, virulence determinants and their role in pathogenesis, as well as the development of innovative therapeutic and prophylactic strategies based on measles virus and targeting notably AIDS and respiratory viruses. The unit is part of CNRS URA 3015.

Dans le cadre d’un Programme collaboratif financé par la région Ile de France réunissant plusieurs équipes franciliennes, un poste de chercheur post-doctoral (géré par le CNRS) est ouvert pour 24 mois dans l’équipe du Dr. Nicolas Escriou (Unité de Génomique Virale et Vaccination, Institut Pasteur, Paris, France). Le programme consiste en l’étude de mécanismes d’adaptation du virus grippal pandémique A/H1N1v (2009) à l’homme, et notamment en l’évaluation du rôle de la réponse immunitaire innée et l’identification des déterminants viraux associés.

Le chercheur post-doctoral aura la responsabilité de la mise au point et de la mise en oeuvre du modèle animal cobaye nécessaire au programme et il contribuera au développement des systèmes de génétique inverse virale ainsi qu’à la réalisation des analyses transcriptomiques chez l’animal et dans la cellule infectée. Ce programme implique la mise en oeuvre d’un ensemble de technologies variées en milieu confiné de niveaux 2 et 3+.

Les activités de l'unité de Génomique Virale et Vaccination, dirigée par le Dr Frédéric Tangy à l’Institut Pasteur à Paris, sont centrées sur l’étude des interactions fonctionnelles virus / hôte, l'analyse des déterminants de virulence et des processus pathologiques associés, ainsi que le développement de nouvelles stratégies thérapeutiques et prophylactiques reposant sur le vecteur rougeole, notamment pour le virus du SIDA et les virus respiratoires. L’unité fait également partie de l’URA 3015 du CNRS.

The Applicant / Le candidat

 We are looking for enthusiastic and highly motivated candidates with a background in molecular virology or viral immunology fields. Prior experience with animal models is preferred. Prior experience in transcriptomics and innate immunity would be an asset but is not strictly required. The successful candidate should be available from October 1st 2011.

Nous recherchons un collaborateur post-doctoral enthousiaste et motivé, possédant une expérience dans le domaine de la virologie moléculaire ou de l'immunologie virale. Une expérience préalable de l’expérimentation animale est fortement souhaitée. Des compétences dans les domaines de la transcriptomique et de l’analyse des réponses immunitaires innées seraient un atout mais ne sont pas strictement requises. Le candidat devra être disponible à partir du 1er octobre 2011.

Net salary: around 2,100 Euros per month. / Salaire : Autour de 2100 € nets mensuels.


Contact

Please send full CV including research interests and 2 or 3 references with contact information to:
 Dr. Nicolas Escriou (nicolas.escriou@pasteur.fr) no later than August 24rd 2011.

Les candidatures comprenant un CV détaillé ainsi que le nom de deux références sont à envoyer à : Dr. Nicolas Escriou (nicolas.escriou@pasteur.fr) avant le 24 août 2011.


01/07/2011 - Role of intracellular TLR9 trafficking and signaling in an inflammation model

A two year position funded by the French National Research Agency (ANR) is available in the Unit Cytokines & Inflammation at Institut Pasteur Paris, starting september 2011. The project is to study the role of intracellular TLR9 trafficking and signaling in an inflammation model. Studies will focus on the analysis of the inflammatory responses in TLR9, Asparagine endopeptidase (AEP) and Cathepsin L (CatL)deficient mice in the course of infection by Leishmania major. The role of these proteases in endosomal TLR stimulation has been previously shown. Their role in the trafficking of TLR and their relevance for the onset of innate and adaptive immune responses in L. major infection will be now investigated.

TLR9-deficient mice (TLR9-/-) are more susceptible to infection with L. major than wild type (WT) C57BL/6 mice. TLR9-/-mice resolve their lesions and control parasites growth with a much lower efficiency than WT. Preliminary data suggest that, in vitro, DCs lacking AEP activity infected by L. major are unable to respond, due to the impaired processing of TLR9. TLR9 processing is impaired in macrophages isolated from Catl deficient mice but not in macrophages lacking AEP. We will compare the susceptibility of AEP-/-, TLR9-/-and CatL-/-mice following inoculation by L. major promastigotes.

In order to establish the impact of TLR9 signaling in DCs and macrophages, we will investigate the development of cutaneous lesion and parasites burden after infection, until the healing of the lesions. We will analyse the recruitment of DCs, macrophages, neutrophils and T lymphocytes as well as proinflammatory cytokines and chemokines expression at the site of infection and in the draining lymph nodes. The orientation of the T cell response by measuring the expression of IFN-γ and IL-4 in T lymphocytes during the course of infection in TLR9, AEP, and CatL deficient mice will be also compared. Purified vertebrate DNA is unable to stimulate TLR9 but it has already been shown that the DNA from some protozoan parasites activate macrophages. Purified L. major DNA also induces the activation of DCs but the mechanism of such activation remains unsolved. Our plans are to determine the origin of the specific TLR9 dependent activation caused by L. major DNA in DCs and in macrophages.

This project is part of an ANR grant investigated by B. Manoury (Necker hospital U1013, coordinator of the project) N. Doyen and L. Touqui, (from the Department of Infection and Epidemiology of Insitut Pasteur, unit Cytokines & Inflammation and unit Innate host defense and Inflammation U 874), respectively.

This project will give important new insights in the field of leishmania research. Annual incidence of cutaneous leishmaniasis is estimated at 1-1.5 million cases worldwide. Overall prevalence of the disease is 12 million people and the population at risk is 350 million people.

The Institut Pasteur, located in the heart of Paris, provides an international and dynamic research environment with state-of-the art imaging and animal colonies facilities.

The Applicant

The applicant should have obtained his/her PhD less than 2 years ago.
The candidate should have strong experience in cell biology, molecular biology , cellular imaging and conceptual
training in immunology and parasitology. The working language is English; strong written and oral
communication skills are required.
 

Funding

CNRS postdoc salary scale (2 years) .

Contact

Please send full CV including research interests and 2 or 3 references with contact information to:
Dr Noëlle DOYEN
Group E3 In Unit of Cytokines and Inflammation
28 rue du Docteur Roux
75724 PARIS Cedex 15
http://www.pasteur.fr/ip/easysite/pasteur/en/research/scientific-departments/infection-and-epidemiology/units-and-groups/cytokines-e-inflammation/index
email: noelle.doyen@pasteur.fr


23/05/2011 - Molecular and cellular biology of Lyssavirus infection

• Description
A three year post doctoral position is available immediately in the Unit Lyssavirus dynamics and host adaptation at the Institut Pasteur in Paris (head: Hervé Bourhy). This unit is involved in research on virus-host adaptation and crossing of the species barrier. This research involves studies on the natural genetic evolution of lyssaviruses and on the molecular basis of lyssavirus virulence.
RNA virus infections kill millions of humans annually, largely due to the lack of suitable vaccines and drugs to control them. This problem is addressed in a FP7 program called: Small molecule Inhibitor Leads Versus Emerging and neglected RNA viruses (SILVER). Within this program you will focus your activities on selected medically important rhabdoviruses and paramyxoviruses for which the development of drugs is considered essential. The aim is to identify the most promising viral protein targets and antiviral compounds. A pipeline strategy has been developed to enable the inclusion in SILVER of viruses at all levels of existing knowledge.
You will have the opportunity to participate in this collaborative project and to use different techniques from virology, cell biology, and functional genomic. Studies will focus on the discovery of compounds with antiviral activity using cell-culture based assays for virus replication, the identification of viral targets and characterization of mechanisms of action of newly discovered antiviral inhibitors, the use of insect and mammalian cell based expression systems to enable the structural analysis of the L polymerase from selected paramyxoviruses and rhabdoviruses and the evaluation of selected antiviral molecules in animal models.

• Qualification
The position is ideally suited for highly motivated and enthusiastic applicants with a PhD and a strong background in virology, molecular and cellular biology, with an established publication record. Strong written and oral communications skills in english are required.

• Additional Information :
Start date : immediately (duration 3 years)
Gross salary: around 2,600 Euros per month
Location : Paris, France
Applicants should send their CV, a list of publication, a summary of their previous research activities (<3 pages), a personnal statement and the names of three referees to the secretary of the unit, E-Mail : edith.martin@pasteur.fr and use the following reference in the subject of the message: PostDoc SILVER.
Website of the unit: http://www.pasteur.fr/recherche/RAR/RAR2009/Dylah-en.html
 

19/11/2010 -  Molecular mechanisms involved in development and function of innate lymphoid cells (ILCs)

Description


A postdoctoral position is available in the Innate Immunity Unit  in the Immunology Department at the Institut Pasteur starting January 2011 to study the molecular mechanisms involved in development and function of innate lymphoid cells (ILCs). ILCs are an emerging family of hematopoietic effector cells that play important roles in immunity and tissue remodeling during fetal and adult life (Spits and Di Santo, Nature Immunology 2010, in press). This three-year position is funded through the ANR (program Blanc, project ’Gut_ILC’).
The Innate Immunity Unit is interested in understanding the molecular events that generate functionally diverse ILC subsets and the roles for these innate effectors in tissue homeostasis, and immune responses against infectious pathogens and cancer. The laboratory has a long-standing interest in natural killer (NK) cell development and function (Di Santo, JP. Annu Rev Immunol 2006) and more recently has discovered novel populations of innate IL-22-producing cells that intervene at mucosal surfaces (Satoh-Takayama et al, Immunity 2008; Satoh-Takayama et al, JEM 2010). The successful applicant is expected to study the molecular mechanisms of ILC development and the roles for ILC subsets in animal models of diseases, using state-of-art instruments and in vivo approaches available in the lab and across the institute. 


QUALIFICATIONS


Interested candidates must be completing or should have obtained a Ph.D. or M.D. degree with background in Immunology, Molecular Biology, Cell Biology, Physiology or a related discipline. The applicant should have record of delivering high-quality research using immunology, molecular biology, and/or animal models. Experience in transcriptional analysis, multi-parameter flow cytometry and/or mouse models are highly desirable but not required. 

SALARY/BENEFITS


These positions are fully supported by the ANR and successful candidates will be offered competitive stipend/salary and benefits commensurate with experience and accomplishments. 

TO APPLY 


 E-mail your CV and at least 3 references to James Di Santo (disanto@pasteur.fr) by December 15, 2010.


12/08/2010 - Role in vivo of chemokine immobilisation on proteoglycans

Description

The project will investigate the role in vivo of chemokine immobilisation on proteoglycans, using the essential chemokine CXCL12 as the paradigm of haptotactic proteins. In particular, the project will explore the role of chemokine/proteoglycan interactions in homeostasis of bone-marrow homing of haematopoietic cells, lymphocyte trafficking and pathological situations associated with tissue regeneration, where CXCL12 plays a hierarchic role of paramount importance. To this purpose an animal model where the chemokine CXCL12 has been selectively disabled to bind on glycosaminoglycans while maintaining intact the agonist capacity, has been developed. The animal model is already available and relies in a number of preliminary results probing the existence of an original phenotype. Furthermore, the project will assess the role played by CXCL12/HS interactions in the physiopathology of tissue repair, and analyze the therapeutic potential of CXCL12 isoforms differing by their capacity to interact with heparan-sulphate proteoglycans.

The project will be conducted under the supervision of Fernando Arenzana-Seisdedos, head of the INSERM U819 unit and Viral Pathogenesis laboratory at the Institut Pasteur in Paris. The project is supported by a 2010-grant from the Agence National pour la Recherche 2010 (ANR-BLANC/Chemrepair).

Experience and skills of the candidate.

The applicant is expected to be highly motivated and enthusiastic and to work independently. The candidate will be in charge, as a priority, of the immunological aspects of the program and subsequently, of the exploration of the regenerative capacities of the muscle in the mutant animals. A strong background in immunology and confirmed expertise animal models are requested. Experience in cellular biology and microscopy imaging techniques will be appreciated and positively evaluated. Gross Salary: 2300 euros/month. Starting from October 2010.

Contact

Applications should be addressed to :
Dr. Fernando Arenzana-Seisdedos
INSERM U818, Institut Pasteur
28, rue Dr. Roux,
Paris 75724 cedex 15.

e-mail address: farenzan@pasteur.fr
telephone: 33 145688263
fax: 33 145688941


12/08/2010 - Etude des mécanismes moléculaires qui sous-tendent l'accroissement de la résistance des virus R5 aux chimiokines au cours de l'infection VIH

Description

 L’étude des mécanismes qui régissent l’entrée du Virus de l’Immunodéficience Humaine de type 1 (VIH-1) dans les cellules cibles est une activité récurrente de notre laboratoire. Lors de cette étape, la sous-unité de surface de la glycoprotéine d’enveloppe du VIH-1, ou gp120, interagit avec le récepteur CD4 puis selon le tropisme viral, avec le corécepteur CCR5 (virus R5) ou CXCR4 (virus X4 ou R5/X4). Les virus R5 sont préférentiellement transmis et prévalent pendant la phase chronique, asymptomatique de l’infection, alors que ceux qui utilisent CXCR4 émergent après quelques années chez la moitié des individus infectés, ce qui est concomitant à l’apparition des signes cliniques du SIDA. Les corécepteurs appartiennent à la famille des récepteurs couplés aux protéines G et sont les récepteurs de chimiokines capables d’activer les protéines G et de mobiliser diverses signalisations intracellulaires. La liaison des chimiokines sur les corécepteurs inhibe aussi l’entrée virale parce qu’elle occlue stériquement celle de la gp120 et parce qu’elle conduit à l’endocytose du corécepteur. Des données de notre laboratoire et de la littérature suggèrent cependant que les virus R5 échappent à l’inhibition par les chimiokines de CCR5 (R5-CCKs) au cours de l’infection. L’objectif principal de ce projet sera d’identifier les mécanismes moléculaires qui sous-tendent le développement de la résistance des virus R5 à l’action des chimiokines au cours de l’infection.
A cette fin, les gp120 d’isolats primaires issus d’un suivi longitudinal sur plusieurs années seront clonées et séquencées. Nous évaluerons l’hypothèse que des variations de la composition nucléotidique du gène env des virus R5 au cours de l’infection VIH sont associées à des modifications de l’efficacité de certaines étapes de l’entrée virale qui pourraient rendre compte de la résistance de ces virus aux R5-CCKs. Pour cela, nous mettrons notamment en œuvre des expériences de pharmacologie et de virologie moléculaires pour la caractérisation des propriétés de liaison aux récepteurs des enveloppes purifiées et radioactives et l’étude de la capacité de différents types de R5-CCKs à inhiber la liaison au corécepteur et l’infection. En outre, l’utilisation de récepteurs CCR5 mutants nous permettra d’évaluer l’hypothèse que l’acquisition de la résistance aux chimiokines est liée à l’utilisation de domaines différents du corécepteur. Nous évaluerons si ce processus s’accompagne aussi de modifications des propriétés fonctionnelles des gp120 . 

EXPERIENCE PROFESSIONNELLE ET QUALIFICATIONS : 

Le candidat devra avoir une forte expérience dans les domaines de la biologie et de la virologie moléculaires. Des connaissances dans le domaine de la pharmacologie des récepteurs couplés aux protéines G seraient un plus. Le candidat devra être très motivé, enthousiaste, savoir travailler de manière autonome mais également être doué d’un fort esprit d’équipe et de qualités relationnelles. 

Contact

Un CV, incluant les domaines de recherche, les techniques expérimentales connues et une liste de publications, et les coordonnées de référents sont à envoyer à : Dr Bernard Lagane (lagane@pasteur.fr ) or Dr Fernando Arenzana-Seisdedos (farenzan@pasteur.fr ), 

Institut Pasteur

Unité de Pathogénie Virale
28 rue du docteur Roux
75724 Paris cedex 15


2/08/2010 - Role of the recombination between enteroviruses in the evolution and emergence of new epidemic strains.

Description

A post-doctoral position is available to study a new model of viral evolution leading to the emergence of epidemic and pathogenic vaccine-derived poliovirus strains through the recombination between vaccine poliovirus strains and coxsackie viruses. The project (ANR) includes the analysis of enterovirus isolates collected in the field (molecular epidemiology), the rational design of strains using genetic engineering technics and the characterization of recombinant viruses. An animal model is available to assess strains pathogenicity. Collaboration with laboratories of the Pasteur Institute International Network and possible short term periods abroad are envisaged.

Recent publications on the subject:

- Jegouic et al.. (2009). Recombination between polioviruses and co-circulating coxsackie A viruses: role in the emergence of pathogenic vaccine-derived polioviruses. PLoS Pathog 5(5), e1000412.

- Rakoto-Andrianarivelo et al., (2007). Co-circulation and evolution of polioviruses and species C enteroviruses in a district of Madagascar. PLoS Pathog 3(12), e191.

- Riquet et al.. (2008). Impact of exogenous sequences on the characteristics of an epidemic type 2 recombinant vaccine-derived poliovirus. J Virol 82(17), 8927-32. 

Contact

To apply, send a full C.V., a brief description of previous works (2 pages max.), the names and addresses of two referees to: 

Francis DELPEYROUX, 
PhD WHO Collaborating Centre of Research on Enteroviruses & Viral Vaccines. 
Biology of Enteric Viruses, 
Inserm U994, 
Institut Pasteur, 
75 724 Paris-cedex 15 - France 
e-mail: francis.delpeyroux@pasteur.fr
Tel: (33) 1 40 61 33 22


21/07/2010 - Role of Chromatin architecture and noncoding RNAs in cellular senescence and tumorigenesis

Description

Applications are invited to fill a postdoctoral position studying the tumor suppressor mechanism cellular senescence in mammalian cells. The potential candidate should have a strong background in general cell and molecular biology techniques and in particular hands-on knowledge in chromatin- as well as small, noncoding RNA research. A basic understanding of bioinformatics would be an asset. The starting date will be decided in agreement with the selected candidate.

Contact

Please, send a letter of intent along with a complete CV including a list of publications and the contact details of three referees to:

Dr. Oliver Bischof
Institut Pasteur
Unité Nuclear Organization and Oncogenesis; INSERM U993
25-28, rue du Docteur Roux
75724 Paris Cedex 15
France

Tel. 33 / 1 40 61 33 07
Fax 33 / 1 45 68 89 43
obischof@pasteur.fr


17/02/2010 - Research on the APOBEC3 cytidine deaminases and the replication of retroviruses and DNA viruses

Description


Three year post-doc position available at the Institut Pasteur, Paris (Molecular Retrovirology Unit) 

The research fellow will carry out research on the APOBEC3 cytidine deaminases and the replication of retroviruses and DNA viruses with particular attention to the cell biology of the deaminases.

Candidates should hold a recent PhD and have experience in molecular and cell biology. The three year position is available as of now. Fluency in English is essential, while a knowledge of French would be useful but is not required.

Contact

A CV and names and addresses of two referees should be submitted by email to Pr. Simon Wain-Hobson (simon.wain-hobson@pasteur.fr)


12/01/2010 - Mechanisms of restriction of HIV-1 replication in human macrophages

Description

Macrophages are major targets of human immunodeficiency virus type 1 (HIV-1) infection. We have previously shown that the induction of the CDK inhibitor p21Waf-1/Cip1 by FcγR-aggregation and other stimuli inhibits the reverse transcription and integration of HIV-1 and related primate lentiviruses in human macrophages (1-3). In continuation with these studies we will now investigate the molecular mechanism by which p21 inhibits retroviral replication.

The candidate is expected to have a strong background in molecular biology and virology. Candidates with practical experience in biochemical analysis of protein interactions and RNA biochemistry will receive strong consideration. The successful candidate will be required to work in the BSL3 facility with competent HIV-1. 

The position is expected to start August 2010, for a 2-years period.

Candidates will join the research team “Factors of natural resistance to HIV-1 infection” of Dr. Gianfranco Pancino, in the Regulation of Retroviral Infections Unit (Director: Prof. Françoise Barré-Sinoussi, Nobel Prize in Medicine 2008)
http://www.pasteur.fr/ip/easysite/pasteur/en/research/scientific-departments/virology/regulation-of-retroviral-infections/regulation-of-retroviral-infections.

Publications relative to the subject :
1. Perez-Bercoff D, et al. Fcγ receptor-mediated suppression of human immunodeficiency virus type 1 replication in primary human macrophages. J Virol. 2003 ;77:4081-94.
2. David, A, et al. The Engagement of Activating Fcγ Receptors Inhibits Primate Lentivirus Replication in Human Macrophages. J. Immunol., 2006, 177:6291-300.
3. Bergamaschi A, et al. The CDK inhibitor p21Cip1/WAF1 is induced by Fc{gamma}R activation and restricts the replication of HIV-1 and related primate lentiviruses in human macrophages. J Virol. 2009 Dec;83(23):12253-65. Epub 2009 Sep 16.
4. Bergamaschi A, et al. The human immunodeficiency virus type 2 Vpx protein usurps the CUL4A-DDB1 DCAF1 ubiquitin ligase to overcome a postentry block in macrophage infection. J Virol. 2009 May;83(10):4854-60. Epub 2009 Mar 4.

Contact

Applications should include a CV, a letter of interest, and contact information of two referees, and submitted by e-mail to: Gianfranco Pancino

 


5/11/2009 - Migration of primary glioblastoma cells

Description

An exciting opportunity exists for a post-doctoral scientist to be part of a collaborative research program between the Cell Polarity and Migration Group (Dr. S Etienne-Manneville) at the Institut Pasteur and the largest center of glioma treatment in France, the Neuro-oncology group (Pr. JY Delattre, Dr. M Sanson) at the Pitié-Salpétrière. The postdoc fellow taking up the position will be based in the Institut Pasteur in Paris.

Glioblastomas are highly angiogenic and invasive tumors and prognosis remains very poor. Invasion is major obstacle for glioblastoma treatment and a growing body of pre-clinical data suggests that anti-VEGF therapy may promote tumor infiltration. It is crucial to understand the molecular events responsible for glioblastoma invasive properties in order to identify attractive targets for developing novel anti-glioblastoma chemotherapeutics.
The key aims of this project are:
- the development new imaging-based assays to analyse the migration properties of primary glioblastoma cells.
- the establishment an in vitro migration assay for drug screening.
- the identification of a molecular signature of invasive gliomas.

We are looking for very motivated scientists with interest and background in cell biology and/or cell imaging. Candidate with experience in vivo studies are also encouraged to apply. The 2-year position is available anytime from January 1010.

Contact

Enquiries and applications (CV and references) may be made to

Sandrine Etienne-Manneville
Cell Polarity and Migration Group
sandrine.etienne-manneville@pasteur.fr
Tel : 01 40 61 39 05


24/09/2009 - Biologie structurale des systèmes de transfert d'ADN au travers de l'enveloppe cellulaire bactérienne.

Description

 

Un emploi post-doctoral est disponible pour travailler sur les systèmes de transfert d’ADN utilisés par les bactéries Gram-positives au cours de la conjugaison et transformation bactérienne. De façon plus spécifique, le projet proposé concerne la purification et la caractérisation structurale (en utilisant la cristallographie RX et/ou la microscopie électronique) de sous-unités ou de complexes protéiques issus des systèmes de conjugaison trouvés chez Staphylococcus aureus et Enterococcus faecalis.

Le/la Candidat/e doit être titulaire d’un doctorat. De solides compétences en biologie moléculaire, biochimie des protéines membranaires ainsi qu’en cristallographie RX ou microscopie électronique sont requises. Un contrat à durée déterminée de 3 ans financé par l’Institut Pasteur est proposé. Le poste est disponible début 2010 et la date de début du contrat sera déterminée avec la personne sélectionnée.

Contact

Un dossier de candidature sous la forme d’un CV, une liste de publication, un bref résumé de l’activité de recherche (4 pages max) ainsi que les coordonnées de deux personnes référentes doit être envoyés par Email à :

Dr Rémi Fronzes
Groupe de recherche G5 “Biologie structurale de la sécrétion bactérienne » Département de Biologie Structurale et Chimie.
Institut Pasteur,
25-28 rue du Docteur Roux
75724 Paris Cedex 15
France

Tel: 00 44 20 7631 6864

Email : r.fronzes@mail.cryst.bbk.ac.uk

Date limite : 1er décembre 2009.


16/07/2009 - Molecular mechanisms involved in the regulation of hepatitis B virus transcription and persistence

Description

Applications are invited for a Post-Doctoral Research Assistant at the Oncogenesis and Molecular Virology Unit at Institut Pasteur, Paris, France.

The hepatitis B virus (HBV) is a small DNA virus that induces acute and chronic liver diseases, and represents a major risk factor for the development of hepatocellular carcinoma. An important step in the regulation of HBV replication is the transcription of pregenomic RNA from covalently closed circular DNA (cccDNA) organized in a chromatin-like structure.

The current project of the laboratory is to further understand how epigenetic modifications regulate transcription of this minichromosome at the different stages of viral infection. We will also investigate whether the transcriptional regulatory protein HBx is involved in such modifications through the recruitment of its cellular partners such as histone acetyltransferases (HATs).

Candidates should have a PhD and should have a proven laboratory track record in all aspects of virology, molecular biology and cell culture. The starting date will be decided in agreement with the selected candidate. The appointment will be financed by a grant from INCA.

Contact

Applications in the form of a CV, publication list and contact details of two referees, should be sent to :

Dr Christine Neuveut
Oncogenese et Virologie moleculaire / U 579 INSERM
Batiment Lwoff
Institut Pasteur
28 rue du Dr roux
75015 Paris
France

Tel. 33 / 1 45 68 88 51
Fax 33 / 1 45 68 89 43
email : christine.neuveut@pasteur.fr

 


Borrelia burgdorferi sensu lato and Ixodes ricinus interactions involved in pathogen transmission to the mammalian hosts

Description

A postdoctoral position is available in the National Reference Centre for Borrelia, Mo-lecular Genetics of Bunyaviruses Unit, in Institut Pasteur, Paris, France.
This research opportunity is to identify, in the European tick-pathogen system (Ixodes ricinus- Borrelia burgdorferi sensu lato), protein interactions of benefit to the tick, the bacterium, or both. Briefly, this main objective will by addressed by complementary peptidomic, proteomic approaches and functional assays, plus the assessment of the effects on virulence and dissemination of European Borrelia strains in an animal model of Lyme borreliosis.

The position is supported by an Institut Pasteur funding guaranteed for at least two years as part of a “Transversal Research Program”. The candidate should have a Ph.D. in a relevant field (e.g. Molecular microbiology or entomology, Genetics, Bio-chemistry, Biology, etc.), and strong experience and documented ability in molecular biology and biochemistry. Applicants should submit by e-mail a letter of motivation and a CV, a summary of research activities (4 pages max) and two letters of professional references.

Contact

Dr Murielle Cornet
Centre National de Référence des Borrelia
Unité de Génétique Moléculaire des Bunyavirus, Institut Pasteur
25, rue du Dr Roux
75724 Paris Cedex 15, France
Tel 33 1 45 68 83 37
e mail : muriel.cornet@pasteur.fr

Or Valérie Choumet
Unité de Génétique Moléculaire des Bunyavirus, Institut Pasteur
25, rue du Dr Roux
75724 Paris Cedex 15, France
Tel 33 1 45 68 86 30
e mail : valerie.choumet@pasteur.fr