PhD position – Molecular imaging of senescent cell burden (Grenoble, France)

A PhD position in radiotracer development and cellular senescence biology is open at Laboratoire Radiopharmaceutiques Biocliniques (LRB, UMR INSERM-UGA U1039, https://lrb.univ-grenoble-alpes.fr/) and TIMC laboratory, Translational microbiology - Evolution - Engineering team (TrEE/TIMC, UMR 5525 CNRS-UGA, https://www.timc.fr/en/tree) from the University Grenoble Alpes. The position is funded for 3 years as a doctoral research allowance (Allocation Doctorale de Recherche) from the Chemistry, Biology and Health (CBH) Graduate School of Grenoble Alps University, supported by the French National Research Agency in the framework of the "Investissements d’avenir” program (ANR-17-EURE-0003).

Cellular senescence is involved in many chronic age-related pathologies, and the destruction of senescent cells (SnCs) has shown a beneficial effect in animal models. The destruction of SnCs in vivo is the principle of senolytic therapies, which is a very active field of research. However, there is no non-invasive way to directly evaluate the SnC burden in situ. Single-domain antibodies (sdAbs) are a class of molecules with excellent characteristics for molecular imaging agents. Nuclear imaging modalities are the techniques of choice for molecular imaging due to their high detection sensitivity. This project aims to develop and evaluate a molecular imaging agent based on sdAbs to monitor SnC burden using nuclear imaging. The project will involve the validation of a marker of SnCs in an animal model of cellular senescence, the development of sdAbs targeting the identified marker by phage display, the production and the purification of selected clones, their characterization, radiolabeling and the evaluation of the radiolabeled sdAbs. These studies will help select the sdAb with the best characteristics which will be further optimized and validated for its efficacy in monitoring SnC burden by molecular imaging in the context of a senolytic treatment.