Molecular insight into antibody-antigen interactions
Antibodies are effector proteins of the adaptive immune system recognizing foreign molecules (antigens) such as microbes, cancer, autoantigens, or vaccine particles. Antibody therapeutics have led to impressive medical breakthroughs in infection, cancer, and autoimmunity. The interface on the antibody that establishes the binding contact with the antigen is called paratope. The antigen part of the 3D-binding interface is called the epitope. Deciphering the rules of paratope-epitope interaction is crucial to achieving the long-standing dream of in silico therapeutics and vaccine design. We are using medium and high-resolution techniques (HDX-MS, X-ray crystallography and cryoEM) to map paratop-epitop interfaces on already established and clinically relevant antibody-antigen (Ab-Ag) complexes (SARS-Cov2, influenza, receptors on cancer cells…). In collaboration with other experimental and computational labs in the area our work will help better understand present antibody-based therapeutics and provide guidance for the design of future ones
In this project, Master student will
make Ab-Ag complexes,
measure hydrogen-deuterium exchange (HDX) in Ab and Ag alone and in Ab-Ag complex and use mass spectrometry to identify regions where exchange is taking place
map HDX regions on already existing structures of Ab and Ag
potentially design X-ray crystallography or cryo-EM experiments to solve the structure of Ab-Ag complex