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How Membrane Physical Properties and Cortical Actin Regulate Protein Interactions During T Cell Signalling

Objective

The overall aim of this project is to identify key biophysical mechanisms that control the spatial arrangement of signalling proteins and membrane lipids in the regulation of T cell activation. During an immune response, T cells are activated in response to antigenic peptides in a process that requires the formation of multi-molecular signalling complexes. It is known that many T cell signalling proteins (such as the kinase Lck and the scaffold protein LAT) are not randomly distributed within the plasma membrane thus giving rise to lateral organization which affects signalling efficiency. However, the biophysical mechanism(s) that control protein distributions and hence the rate of molecular interactions remains poorly understood. Two of the principal mechanisms are compartmentalisation of the membrane by lipid microdomains (the ‘lipid raft’ hypothesis) and by the cortical actin meshwork (the ‘picket-fence’ model). The two key technologies needed to unravel how protein clustering and the biophysical properties of the lipid bilayer regulate specific interactions at the molecular level have now been developed. These are single-molecule, super-resolution localisation microscopy and quantification of membrane biophysical properties using new-generation environmentally sensitive fluorescent probes. Using these methods, the proposed project will generate unique insights into the biophysical mechanisms that govern the formation of the protein clusters and complexes during early T cell signalling events. This knowledge is critical to our understanding of the molecular basis of T cell activation during the immune response and has potential applications in the development of therapeutic treatments for a range of conditions.

Field of science

  • /natural sciences/biological sciences/biochemistry/biomolecules/lipids
  • /natural sciences/biological sciences/biochemistry/biomolecules/proteins
  • /natural sciences/biological sciences/cell biology/cell signaling

Call for proposal

ERC-2013-StG
See other projects for this call

Funding Scheme

ERC-SG - ERC Starting Grant

Host institution

KING'S COLLEGE LONDON
Address
Strand
WC2R 2LS London
United Kingdom
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 1 402 513
Principal investigator
Dylan Myers Owen (Dr.)
Administrative Contact
Paul Labbett (Mr.)

Beneficiaries (1)

KING'S COLLEGE LONDON
United Kingdom
EU contribution
€ 1 402 513
Address
Strand
WC2R 2LS London
Activity type
Higher or Secondary Education Establishments
Principal investigator
Dylan Myers Owen (Dr.)
Administrative Contact
Paul Labbett (Mr.)