Mechanisms of apoptosis in metazoan cells

As in a company restructure, a body remodeling itself during growth must not only recruit, by cell division and specialization, but also retrench, by killing off redundant cells. In adult animals too, normal and pathogenic processes can lead to an overabundance of cells that demands judicious pruning. Intriguingly, all doomed cells basically die by their own hands, undergoing suicide via co-ordinated, multi-step programs - apoptosis. Early work showed that the terminal stages of apoptosis are amazingly well conserved throughout evolution, from worms to humans. For every cell the suicidal tendency is actually an ever-threatening facet of its make-up. Minute-to-minute, each cell weighs up a multitude of internal and external signals, some favouring existence, others oblivion. Recently, the variety of potential signals, and also the differing signal-sensitivities of cells, have drawn attention to an unexplored multiplicity of pathways that converge upon the conserved core. We work on an ideal system to investigate these non-core pathways: human T cells. T cells serve in squads that target specific antigens, then self-destruct, yet manage to leave behind a few operatives primed to handle similar subsequent attacks. Working in unpredictable microenvironments, they respond flexibly to a wide repertoire of survive-or-suicide cues, as is also true for their different developmental stages. Using these adaptable, experimentally amenable cells our lab has helped to confirm that an unexpected group of cellular intermediates - reactive oxygen species - are critical for apoptosis in mature T cells. Our main goal now is to detail how these intermediates engage with previously characterized T cell termination pathways.

Recent Publications:

Marcel N, Perumalsamy L, Shukla S and Sarin A
The lysine deacetylase Sirtuin 1 modulates the localization and function of the Notch1 receptor in regulatory T cells.
Science signaling 2017, 10 (473) eaah4679.;10/473/eaah4679?...

Marcel N and Sarin A
Notch1 regulated autophagy controls survival and suppressor activity of activated T-regulatory cells.
eLife 2016;5:e14023

Sarin A and Marcel N
The NOTCH1-Autophagy Interaction:Regulating self-eating for survival.
Invited article commentary in “Autophagic Puncta” for Autophagy, 2016, Issue 2 (p446-447) doi: 10.1080/15548627.2016.1268303