Doctorant

Is the Job related to staff position within a Research Infrastructure?: No

Offer Description

The PhD candidate will be based at the IPBS site. The project will be carried out within the “Phagocyte Architecture and Dynamics” team (Renaud Poincloux and Christel Vérollet), with access to all the resources and methodologies available within the team and the institute.

The proposed research programme will be conducted under the supervision of Drs. Fabrice Dumas and Christel Vérollet. Our team has established a collaboration with the group of Dr. P. Escribá in Spain, a pioneer in the development of the MLT concept.

Safety conditions will comply with the internal regulations of IPBS.

Macrophages play a central role in HIV-1 persistence by supporting productive infection, cell-to-cell viral transmission, and the sequestration of viral particles within specialized compartments known as viral-containing compartments (VCCs). Interactions between macrophages and infected CD4⁺ T lymphocytes further promote viral dissemination through specialized actin-rich membrane structures, including tunneling nanotubes (TNTs) and virological synapses. Since all these processes depend on plasma membrane remodeling and membrane–cytoskeleton interactions, the macrophage membrane may represent an attractive target for the development of host-directed antiviral strategies.

Membrane lipid therapy (MLT) is an innovative approach that exploits the ability of certain lipids, particularly polyunsaturated fatty acid derivatives (D-PUFAs), to alter membrane organization and cellular signaling. MLTs have demonstrated therapeutic potential in cancer and other diseases, but their antiviral potential remains largely unexplored. Our preliminary data show that certain D-PUFAs inhibit HIV-1 infection in a cell-type-dependent manner, providing a strong rationale for investigating how membrane lipid remodeling may interfere with HIV-1 infection and persistence, particularly in macrophages.

The overall objective of this PhD project is to determine whether and how MLT compounds can inhibit HIV-1 infection of macrophages while preserving their physiological functions. Demonstrating this functional selectivity is an essential prerequisite for considering membrane lipid remodeling as a host-directed antiviral strategy.

We will evaluate a panel of D-PUFAs for their ability to inhibit infection and selectively target HIV-1-infected macrophages, using both monocyte-derived macrophages and alveolar macrophages, which are more physiologically relevant. We will also investigate the effects of these compounds on key macrophage functions, including podosome formation, migration, and phagocytosis.

The most promising compounds identified will then be selected for mechanistic studies, in which we will investigate their effects on macrophage fusion, VCC formation, and cell-to-cell viral spread. By identifying membrane-dependent mechanisms that can be exploited to disrupt HIV-1 infection and persistence in macrophages, this project will provide proof of concept for MLT as a novel antiviral strategy.

Beyond HIV-1, these findings could also provide a basis for exploring the broader antiviral potential of membrane lipid remodeling against other viruses.

Where to apply

Website: https://emploi.cnrs.fr/Offres/Doctorant/UMR5089-CHRVER-006/Default.aspx

Requirements

Research Field: Biological sciences — Education Level: PhD or equivalent

Research Field: Medical sciences — Education Level: PhD or equivalent

Research Field: Pharmacological sciences — Education Level: PhD or equivalent

Languages: FRENCH — Level: Basic

Research Field: Biological sciences — Years of Research Experience: None

Research Field: Medical sciences — Years of Research Experience: None

Research Field: Pharmacological sciences — Years of Research Experience: None

Additional Information

Website for additional job details: https://emploi.cnrs.fr/Offres/Doctorant/UMR5089-CHRVER-006/Default.aspx

Work Location(s)

Number of offers available: 1

Company/Institute: Institut de Pharmacologie et Biologie Structurale

Country: France

City: TOULOUSE

Contact

City: TOULOUSE

Website: http://www.ipbs.fr