# Mechanisms of translational regulation by the unfolded protein response

> **NIH NIH K99** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2022 · $100,000

## Abstract

Project Summary/Abstract
Summary of Research Project: Protein folding is one of the most critical nodes of cellular health and cells
employ dedicated machineries comprised of transcriptional, co-translational and post-translational mechanisms
to ensure all proteins are correctly folded and the incorrectly folded proteins are rapidly triaged. The
endoplasmic reticulum (ER) is the site of folding and maturation of the majority of transmembrane proteins and
secreted proteins, and its dysfunction is linked to a dozen different diseases including diabetes,
neurodegenerative diseases and cancer. Recent work suggests that IRE1 is physically linked to the
translational machinery. This finding opens an entire new field of translational regulation by IRE1 and possibly
by other UPR sensors. In this proposal, I will gain high-resolution insights in this newly discovered mode of
translational regulation at the ER.
Career Development Plan and Environment: As a graduate student in David Eisenberg’s lab at UCLA, I
investigated the toxic conformational states in the protein aggregation pathway using X-ray crystallography. I
have continued my training in the field of protein folding by taking a cell biological approach working in the lab
of Dr. Peter Walter at UCSF. I will continue my professional development by learning the latest techniques in
CryoEM and functional genomics. Under the mentorship of Dr. David Agard, a pioneer in the methods for
single-particle cryoEM, Dr. Peter Walter, an expert in the field of UPR and IRE1 biology and with advise and
guidance from Dr. Stephen Floor, a functional genomics expert, I will gain significant training that will ultimately
help me transition to an independent research career.
Career Goals: My career goal is to establish a research program investigating the fundamental mechanisms of
protein folding in cells. How cells manage partially folded and misfolded proteins, the mechanism employed to
fine-tune translation of specific genes to prevent overwhelming the protein folding machinery and how cells
correct chronic build-up of protein aggregates are some of the questions that I will address in my independent
research.

## Key facts

- **NIH application ID:** 10449925
- **Project number:** 1K99GM143527-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Smriti Sangwan
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $100,000
- **Award type:** 1
- **Project period:** 2022-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10449925

## Citation

> US National Institutes of Health, RePORTER application 10449925, Mechanisms of translational regulation by the unfolded protein response (1K99GM143527-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10449925. Licensed CC0.

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