TCELLTIGIT | Structural characterization of immune signaling protein TIGIT using x-ray crystallography and cryo-electron microscopy

Summary
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.
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More information & hyperlinks
Web resources: https://cordis.europa.eu/project/id/790144
Start date: 01-01-2019
End date: 31-12-2020
Total budget - Public funding: 175 866,00 Euro - 175 866,00 Euro
Cordis data

Original description

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.

Status

TERMINATED

Call topic

MSCA-IF-2017

Update Date

28-04-2024
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Horizon 2020
H2020-EU.1. EXCELLENT SCIENCE
H2020-EU.1.3. EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions (MSCA)
H2020-EU.1.3.2. Nurturing excellence by means of cross-border and cross-sector mobility
H2020-MSCA-IF-2017
MSCA-IF-2017