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How Membrane Physical Properties and Cortical Actin Regulate Protein Interaction...

How Membrane Physical Properties and Cortical Actin Regulate Protein Interactions During T Cell Signalling 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 a... ver más

31/01/2019

KINGS COLLEGE LOND...

1M€

Presupuesto del proyecto: 1M€

Líder del proyecto

KINGS COLLEGE LONDON No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Fecha límite participación Sin fecha límite de participación.

Financiación concedida El organismo FP7 notifico la concesión del proyecto el día 2019-01-31 No tenemos la información de la convocatoria

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1 Participantes

KINGS COLLEGE LONDON

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Líder del proyecto

KINGS COLLEGE LONDON No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 1M€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto 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.

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