Biology

Sudha Kumari, PhD
Massachusetts Institute of Technology, Cambridge, USA

Efficient cellular communication is a fundamental demand of an effective immune response, where direct cell-cell contacts mediate the majority of the immune cellular recognition events. Such transient cellular junctions, classically termed ‘immunological synapses’, are unique to immune cells. Synapse duration and strength are critical determinants of the quality and magnitude of the subsequent immune response. While the biochemical tool parts required to engage successful immunological synapse are substantially well -characterized; mechanistically how these components orchestrate the lifetime and mechanics of immune cell contacts remains unclear. We investigated this problem using primary T cells as model cells, and a combination of interdisciplinary techniques including genetic perturbations, in vitro cellular mimetic surfaces and high-resolution microscopy. Our results uncovered a novel cytoskeletal pathway that mechanically tunes cell-cell contact stability in T cells. Loss of this cytoskeletal pathway results in short lived synapses, poor T cell immune response, and is associated with an immunodeficiency disease in humans. Furthermore, we find that the aforementioned cytoskeletal mechanism for modulating contact lifetime is not unique to the T cells. A variation of the same mechanism could also be utilized during the immune cell-tumor cell interactions during tumor metastasis, and could restrain the success of tumor cell metastatic seeding into distant organs.
In my talk, I will discuss the aforementioned cytoskeletal mechanism that modulates immune cell contact lifetime, using the two above mentioned case studies: The T cell immunological synapse and the tumor cell- granulocytes aggregation during metastasis. I will also briefly outline the development of an optical clearing technique that enables sensitive and high resolution imaging of immune cell contacts in their native environment, deep within the intact organs.