PhD (CIFRE) position – SANOFI & ESRF on cryoEM methods applied to antibodies
PhD thesis title: High resolution Cryo- Electron Microscopy of Antibody / Antigen complexes
More and more research focus is being put on biologics and their development as drugs. These molecules are usually large and flexible and they can interact with various targets located on the surface of cells; Bi-specific antibodies are an example that can potentially bind to two different antigens and which have gained attention due to their potential application in cancer immunotherapy and drug delivery. To fully understand their mechanism, structural knowledge at an atomic level is needed.
While low resolution studies can be obtained using traditional microscopy, high resolution studies of these interactions are usually performed by protein crystallography (or by Hydrogen Deuterium Exchange studies) using fragments of both antibody and antigen. The ESRF is in progress of installing a Krios microscope which, coupled with a direct electron detector and a Volta phase plate will enable us to determine the full structure of the complexes.
The successful candidate will characterise Ag/Biologics complexes from Sanofi, using state-of-the-art microscopes at the cryo-EM platform of the Partnership for Structural Biology (PSB) and will determine the high-resolution structure of one or more of these complexes.
The PhD thesis will last 3 years starting in late autumn 2017, in a collaboration between Sanofi (Vitry sur Seine, France) and the ESRF (Grenoble, France) under the co-supervision of Dr. Magali Mathieu (Sanofi) and Dr. Gordon Leonard (ESRF). This thesis will be CIFRE (Conventions Industrielles de Formation par la REcherche) and the student will be a Sanofi employee (CDD) for the whole duration of the thesis. Most of his/her work will be performed at the ESRF.
The applicant must have a Master Degree (Master2 or MSc) in integrated structural biology or biophysics, some knowledge in cryo-electron microscopy and in molecular and cell biology. He/she should be a team player and have good communication skills.
Bio Structure and Biophysics / iDD France
Centre de Recherche de Vitry/Alfortville