| Project Detail |
The goal of this proposal is to obtain atomic resolution structures of TIGIT using X-ray crystallography and cryo-electron microscopy. TIGIT inhibits autoimmune responses, and anti-TIGIT antibodies can induce immune response in anti-viral and anti-tumor immunotherapies. No structures exist for the transmembrane (TM) domain of TIGIT, which is the portion of the signaling protein that transmits signals accross the membrane bilayer, and there are no structures of TIGIT bound to anti-TIGIT antibodies. High-resolution structures of full-length TIGIT and TM domain constructs will further our understanding of how TIGIT transmits signals across the cell membrane and modulates T cell activation. Structures of TIGIT TM constructs bound to PVR and anti-TIGIT antibodies will guide the design of anti-TIGIT drugs and antibodies for use in immunotherapy treatments. The candidate will carry out this structural work in the lab of Prof. Martin Caffrey, a world- renowned leader in the field of membrane protein X-ray crystallography.
|
