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Matthieu Grégoire, Simon Palayret

Research Interests

 Supervisor: Professor David Klenerman

I am in the third year of the 4-year Infection & Immunity Wellcome Trust PhD programme. I am interested in the very initial triggering of the T cell receptor (TCR), when a T cell recognises an antigen-presenting cell. Different models have been proposed to understand how the extra-cellular signal (binding of the MHC-peptide complex to the membrane TCR) is transmitted through the T cell membrane to an intracellular activation signal (phosphorylation of the TCR, ZAP70 and further Calcium release): the aggregation, the conformational change and the kinetic-segregation models.
During my PhD I have built and characterised a PALM/STORM super-resolution microscope with Dr Steven F Lee to further investigate the formation of the contact between a T cell and either a glass IgG-coated coverslip, a lipid bilayer or an antigen-presenting cell. The super-resolution instrument unravels the very early events leading to TCR triggering giving snapshots of contact zones with a 10 nm resolution. This helps us study undescribed ring structures characteristic of the kinetic-segregation hypothesis, in collaboration with Professor Simon Davis in Oxford. I am finally also developing a method to precisely count the number of proteins in a contact zone to study the aggregation hypothesis.

Keywords

super-resolution ; T cells ; MHC ; single molecule imaging ; TCR triggering ; kinetic segregation ; antigen presentation ; T cell receptor (TCR)

Topics

  • infectious diseases

Key Publications

Etheridge TJ, Boulineau R, Herbert A, Watson AT, Daigaku Y, Tucker J, George S, Jönsson P, Palayret M, Lando D, Laue E, Osborne MA, Klenerman D, Lee SF, Carr AM. Quantification of DNA-associated proteins inside eukaryotic cells using single-molecule localization microscopy. Nucl. Acids Res. 2014;gku726-

Review: Palayret M, Horrocks MH, Klenerman D, Lee SF. The changing point-spread-function: single-molecule based super-resolution imaging. Histochem. Cell Biol. 2014 Jun;141:6(577-85)

Restif O, Goh YS, Palayret M, Grant AJ, McKinley TJ, Clark MR, Mastroeni P.  Quantification of the effects of antibodies on the extra- and intracellular dynamics of Salmonella enterica. J R Soc Interface. 2012 Dec 12;10(79):20120866.

Bell L, Seshia A, Lando D, Laue E, Palayret M, Lee SF, Klenerman D. A microfluidic device for the hydrodynamic immobilisation of living yeast cells for super-resolution imaging. Sensor Actuat. B-Chem. 2014;192(36-41)