PhD Position (M/F): REPROGRAMMING HOST MEMBRANE DYNAMICS AS AN ANTIVIRAL STRATEGY

Job Description

Thesis Subject

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.

Your Work Environment

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..

Constraints and risks

Work will be conducted in a Biosafety Level 3 (BSL-3) laboratory.

Compensation and benefits

Compensation

2300 € gross monthly

Annual leave and RTT

44 jours

Remote Working practice and compensation

Pratique et indemnisation du TT

Transport

Prise en charge à 75% du coût et forfait mobilité durable jusqu’à 300€

About the offer

About the CNRS

The CNRS is a major player in fundamental research on a global scale. The CNRS is the only French organization active in all scientific fields. Its unique position as a multi-specialist allows it to bring together different disciplines to address the most important challenges of the contemporary world, in connection with the actors of change.

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