High-Resolution Imaging to Unravel the Molecular Etiology of Disturbed T-Cell Antigen
T-cell defects account for ~30% of inherited human immune deficiencies. While recent progress in genome sequencing has helped identify gene defects in patients with compromised T-cell antigen sensitivity, the precise molecular underpinnings remain often elusive. This complicates the search for best therapy options for patients with frequent infections and/or organ-destructive autoimmunity. Here we propose a cutting-edge molecular imaging platform to unravel disease-causing mechanisms in patient T-cells. We will devise a planar supported lipid bilayer (SLB) system, which closely mimics the physiological context of T-cell recognition and greatly facilitates single molecule and superresolution microscopy.
We expect that high-resolution functional imaging will enable us to quantitate binding, signaling and redistribution defects of key receptors, effector proteins and cytoskeletal components and help us stratify human T-cell disorders according to TCR-proximity. We will integrate imaging with state-of-the-art high-throughput genomics to identify causative mutations and with interaction proteomics to place identified genes into regulatory networks, which we will in turn verify by functional high-resolution imaging. Ultimately this hybrid approach will fill a critical gap for patients suffering from inherited T-cell defects of so far unknown etiology, enabling discovery of new genes involved in T-cell function and the development of personalized therapeutic strategies.
This thematic programme concentrates on projects, endowed chairs and Vienna Research Groups in the research fields of biology, biotechnology, medicine, veterinary medicine, pharmacy, bioenginering and related fields. One focus is on elucidating molecular mechanisms and methods and/or the development of associated methods; another is on aspects of clinical research.
The Fund also emphasises work to improve links between life sciences and other natural sciences, and in particular modelling issues. Funded research should result, in the medium range, in an improvement of human health and welfare or the protection of our environment.
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