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PhD in Biochemistry and host-pathogen interaction

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Français - Anglais

Date Limite Candidature : mardi 10 août 2021

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General information

Reference : UMR5089-EMILAY-004
Workplace : TOULOUSE
Date of publication : Tuesday, July 20, 2021
Scientific Responsible name : Layre Emilie
Type of Contract : PhD Student contract / Thesis offer
Contract Period : 36 months
Start date of the thesis : 1 October 2021
Proportion of work : Full time
Remuneration : 2 135,00 € gross monthly

Description of the thesis topic

According to the World Health Organization, Tuberculosis remained one of the top 10 causes
of death worldwide in 2018 (1.4 million deaths) (1). M. tuberculosis (Mtb) infects alveolar
macrophages and is extremely successful in establishing a chronic infection in humans.
Indeed, it has evolved strategies to evade immune responses and to persist within the hostile
intracellular environment (2). The current lack of efficient anti-tuberculosis strategies is largely
due to our incomplete understanding of the host-pathogen interactions of Mtb infection. One
characteristic of mycobacteria is the biosynthesis of a highly diverse repertoire of lipids and
glycolipids capable to regulate host immune responses, acting as pathogen-associated
molecular patterns, virulence factors or T cell antigens (3, 4). However, this repertoire of potent
immunomodulators has been essentially characterized by studying bacteria broth cultures and
using conventional biochemistry methods of moderate resolution and sensitivity. We have setup a last-generation lipidomic approach, comprising high sensitivity mass spectrometry and
bioinformatics tools, which allows studying this repertoire in a global and exhaustive way in
diverse conditions (5, 6). Applied to the analysis of in vitro cultures but also to infected cells,
such approach has already highlighted several new molecules of unknown structure and
functions including molecules that are specifically produced by virulent M. tuberculosis strains.
The characterization of such molecules might reveal new immunomodulatory mechanisms and
give rise to new concepts for the development of anti-TB tools. Hence, this project aims at:
- purifying molecules highlighted by lipidomic analyses (cell/mycobacterial cultures, normal and
reverse phase chromatography)
- characterising their structure through the use of state-of-the-art biochemistry tools available
at the IPBS and at the MetaToul platform (bioinformatics, mass spectrometry, MS/MS, NMR,
capillary electrophoresis)
- achieving the functional characterisation of the newly identified bacterial molecules, in
particular their capability to interact with innate immune receptors and to regulate
macrophages inflammatory and microbicide properties (ELISA, reporter cell lines activation
assays and functional bioassays on primary cells)

Work Context

This project will be carried out in the team "Immunomodulation by lipids and mycobacterial glycoconjugates" led by Dr. J. Nigou, in the "Tuberculosis and Infection Biology" department of the Institute of Pharmacology and Structural Biology (IPBS, joint research unit CNRS-Universite Paul Sabatier, Toulouse, France). The student will work under the supervision of Drs. Emilie Layre (CR, CNRS) and Martine Gilleron (DR, CNRS). The IPBS offers a stimulating research environment and benefits from several state-of-the-art facilities on site, including proteomics and mass spectrometry, macromolecular crystallography, liquid and solid state NMR, high resolution imaging of tissues and cells
imaging of tissues and cells, flow cytometry and cell sorting in standard
in standard or level 3 security laboratories and animal facilities.
The IPBS is located on the main campus of the University Toulouse III-Paul Sabatier. which offers multidisciplinary education in the fields of science health, engineering and technology, and is developing one of the most important scientific research centers in France. Founded in 1996, the IPBS is today composed of 16 internationally recognized research groups, which bring together more than 250 scientists, including numerous post-doctoral fellows and national and international PhD students.

Constraints and risks

The student will be trained to perform experiments in closed environment.

Additional Information

This thesis project is funded by a grant from the ANR. Motivated candidates with a Master's degree in Biochemistry, Cell Biology or Analytical Chemistry must provide a CV, an official transcript of their Master's grades, a letter of motivation and the e-mail contact of referees who supervised their work in the laboratory.

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