Rahul Samant
Cellular accumulation of misfolded proteins is a hallmark of ageing. In young cells, the proteostasis network limits toxicity by activating one or more systems for misfolded protein clearance. We focus on how these clearance systems are integrated within the network to maintain proteome health during youth, and how their dis-integration contributes to cellular senescence—another ageing hallmark with strong links to chronic inflammation and organismal frailty.
We currently use two evolutionarily distant cell types—budding yeast and primary human fibroblasts—to identify common, conserved lines of communication between different clearance systems of the proteostasis network, and how these get re-wired during replicative ageing (yeast) and senescence (mammals). Our lab employs multi-disciplinary approaches such as super-resolution imaging, flow cytometry, and mass-spectrometry-based proteomics to measure proteostasis capacity and senescence phenotypes as quantitatively and robustly as possible. As proteostasis modulators hold therapeutic promise in ageing-associated pathologies—with renewed interest in ‘senolytics’ specifically targeting senescent cells—we hope to drive fundamental discoveries that have a direct impact on promoting lifelong health.
We use a multi-disciplinary approach (left panel), using high-resolution imaging, flow cytometry, and mass spectrometry-based proteomics, to probe the relationship between loss of proteostasis and onset of senescence—two of the hallmarks of ageing (middle—adapted from Lopéz-Otín et al., 2013). Our current focus is on the interplay between different protein clearance systems in young vs. senescent cells (right).
Check out Rahul’s talk from Methuselah Health UK’s Conference on Why We Age (2020), entitled “Why we turnover our proteins (and how it gets done)"
Latest Publications
Native mass spectrometry analyses of chaperonin complex TRiC/CCT reveal subunit N-terminal processing and re-association patterns. Scientific reports, 11, 1, 22 Jun 2021 PMID: 34158536 |
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Alternative systems for misfolded protein clearance: life beyond the proteasome. The FEBS journal, 1, 1, 01 Nov 2020 PMID: 33135311 |
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Dosage compensation plans: protein aggregation provides additional insurance against aneuploidy. Genes & development, 33, 1549-5477, 2019 PMID: 31371460 |