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Nano -structural and -dynamic events in the T-cell activation

Objective

The organization of the T-cell in its resting and activated state, specifically of plasma-membrane molecules involved in the triggering of the T-cell, is a long-standing and contentious research topic in molecular immunology. Understanding the molecular mechanisms involved at the nanoscale, i.e. at spatial scales below the resolution limit of conventional optical microscopy (< 200 nm) will find answers to still open questions, and offer new routes to immunotherapy. The proposed multidisciplinary project aims to bring close together super-resolution STED microscopy and membrane biophysics with molecular immunology. The proposed studies will follow a holistic approach and include the investigation of the functional associations of a multitude of molecules in T-cell triggering, ranging from the T-cell receptor and co-receptors, over other proteins such as kinases and phosphatases, to lipids and the cortical cytoskeleton. Using super-resolution STED and single-molecule microscopy (specifically STED and fluorescence correlation spectroscopy, STED-FCS) I will directly observe, determine, follow and evaluate nanoscale molecular interactions of these molecules from the resting state and early activation of the T-cell until the constitution of the immunological synapse. Besides a sophisticated design of the experimental conditions such as appropriate live-cell fluorescence labeling, biochemical treatments and choice of activating the T-cell, I will improve the STED-FCS technology towards multi-color observations allowing the determination of nanoscale dynamics and interactions of different specific molecules at the same time. With new molecular interactions highlighted, I will be able to better understand how T-cells sense antigen presenting cells and what molecular ramifications are involved during the constitution of the immunological synapse.

Call for proposal

FP7-PEOPLE-2013-CIG
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Coordinator

SCIENCE AND TECHNOLOGY FACILITIES COUNCIL
Address
Polaris House North Star Avenue
SN2 1SZ Swindon
United Kingdom
Activity type
Public bodies (excluding Research Organisations and Secondary or Higher Education Establishments)
Administrative Contact
Richard Glover (Mr.)

Participants (1)

THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD

Participation ended

United Kingdom
EU contribution
€ 100 000
Address
Wellington Square University Offices
OX1 2JD Oxford
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Stephen Conway (Dr.)