Spatial Organization of Biological Fuctions | BPS Thematic Meeting

Spatial Organization of Biological Functions Meeting

Thursday Speaker Abstracts

SPATIOTEMPORAL PERTURBATION OF THE T-CELL ACTIN CYTOSKELETON Srishti Mandal 1 ; Alka Chahal 2 ; Michael Mak 3 ; Sarit Agasti 2 ; Sudha Kumari 1 ; 1 Indian Institute of Science, Bengaluru, India 2 Jawaharlal Nehru Centre for Advanced Scientific Research, Bengaluru, India 3 Stonybrook University, New York, NY, USA Immune cells, such as T-cells, must perform immunosurveillance for healthy immunity. A crucial step during T-cell immunosurveillance that underlies the adaptive immune response is the formation of a specialized cell-cell contact interface, between a T-cell and its target, known as the immunological synapse. It is a highly dynamic interface where precise recruitment and regulation in space and time of surface receptors and signaling molecules, integrated with constant remodeling and repositioning of cytoskeletal elements, dictates an optimal immune response. The actin cytoskeleton is one such indispensable element, and T-cells are known to display a diverse repertoire of actin architectures and dynamics, however, the structure-function relationship between actin networks and their roles during synapse progression, is poorly established. Indeed, how the unit filament network may enable a vast variety of functions at a given time and place at the synapse, remains an outstanding question. A primary reason for this gap is that the tools for perturbation of selective actin architectures in a spatiotemporally controlled fashion are currently lacking. The routine ablation of the cytoskeleton using pharmacological inhibitors or genetic perturbations does not provide spatial or temporal control and leads to gross network perturbation. To address the mechanistic gap, we developed a novel photo-sensitive inhibitor, that can ablate actin in a defined space, at a given time, on demand. I will present unpublished data on characterization of the novel perturbation agent, using in-silico, in-vitro, and ex-vivo assays, in which actin was manipulated at an unprecedented spatiotemporal resolution at multi-cell, single-cell, and subcellular levels. Finally, I will present the insights into T cell synapse biology and sub-cellular actin dynamics achieved using the inhibitor with implications for not just immune cells, but for other cellular systems where a temporally controlled and spatially scalable manipulation is desired.

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