Richa Sardana

I work as a postdoctoral researcher in the lab of Scott Emr at the Weill Institute of Cell and Molecular Biology at Cornell University.

I am fascinated by the question of how proteins are recognized as functional or aberrant/damaged/non-functional by cellular protein quality control mechanisms. How do cellular QC mechanisms make these decisions? What features of the proteins are recognized? And what features of the QC machinery provide them the ability to make the distinction? This becomes even more relevant in pathological conditions where damaged proteins are not efficiently removed resulting in accumulation of protein aggregates inside the cells.

Before coming to Cornell, I worked with Ron Kopito at Stanford University to understand protein quality control mechanisms at the Endoplasmic Reticulum. I did my PhD at UT Austin, where I studied the early steps critical in the biogenesis of the eukaryotic small ribosomal subunit and was advised by Arlen Johnson.

I am passionate about science and art. While science is what fills most of my time, art takes up a large part of my free time.

More about Richa.

A picture of Cornell University's McGraw tower in winter.

Posts

I occassionally post my thoughts on interesting science papers and activities I am excited about. There’s the three most-recent posts below, or here’s all posts by year.

Recent Posts

Happy New Year and check out the Ithaca Murals website

06 Jan 2019
public art murals Ithaca Links

Check out the Ithaca murals website if you haven’t visited it already. Caleb et al. have done a wonderful job putting together a murals map that you could refer to. Great idea for organizing a group mural walk/ bike ride! Ithaca murals website link

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Research paper highlight- Translocon Declogger Ste24 Protects against IAPP Oligomer-Induced Proteotoxicity

14 Mar 2018
Science Journal Club protein quality control yeast

Translocon Declogger Ste24 Protects against IAPP Oligomer-Induced Proteotoxicity.

Kayatekin et. al., Cell 173, 1-12, March 2018

Islet amyloid polypeptide (IAPP) is a small peptide secreted by the pancreatic β islet cells. It is thought to regulate the function of the islet cells by inhibiting insulin secretion. It was discovered (and named) due to its tendency to aggregate into insoluble amyloid fibrils in patients with type 2 diabetes (T2D). Subsequent work showed that the cytotoxicity was contributed by smaller, intracellular oligomeric intermediates of IAPP, not the mature amyloid fibrils. Yet what aspect of cellular biology is impacted by these toxic oligomers has remained unclear.

Kayatekin and colleagues report that IAPP-induced proteotoxicity is in part contributed by the clogging of the endoplasmic reticulum (ER) translocon, and can be rescued by translocon associated transmembrane protease Ste24 in yeast or its human homolog ZMPSTE24. Ste24/ZMPSTE24 were recently discovered to directly interact with clogged translocons and cleave jammed proteins.

In order to understand IAPP toxicity, the authors took advantage of the cell death associated with the expression of an oligomeric version of the IAPP peptide in budding yeast, Saccharomyces cerevisiae. Using complementary genetic screens the authors found that functional Ste24 protease was critical for alleviating IAPP toxicity in yeast. The suppression by Ste24 was specific to IAPP and did not mitigate the toxicity caused by other aggregation prone proteins such as α-synuclein or TDP-43. Emphasizing the conservation of the declogging function, overexpression of the human homolog ZMPSTE24 in yeast lacking Ste24 could efficiently rescue IAPP toxicity. Using their yeast model for assaying declogging capability, the authors analyzed 111 ZMPSTE24 single nucleotide polymorphisms discovered in T2D patients and non-diabetic controls and found an enrichment of loss-of-function mutations among people with T2D (although somewhat mild).

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Check out Traffic Light Cook's cooking motivation

10 Feb 2018
Food Granola Links Personal

Garima Lal who writes this great blog on heathy eating and cooking practices, featured me on one of her ‘Cooking Motivation’ series! Check out the post here.

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Projects

I try to experiment with design and hobby projects and I will try to document them whenever I can. The full list is here.