# Perturbing and Sensing Changes to Complex Pathways

> **NIH NIH P41** · UNIVERSITY OF WASHINGTON · 2021 · $312,823

## Abstract

Project Summary
In TR&D 1, we develop approaches to make complex changes to cells, and we generate biosensors to report
on the effects of some of these changes. In the first aim, we establish strategies to rapidly and combinatorially
up- or down-regulate a set of genes in a common pathway in order to improve the expression of a desired
protein, and optimize these approaches using a vaccine protein that is commercially made in yeast. In the
second aim, we devise new selections for use in chemostats and turbidostats to identify the effects of small
changes in proteins, in promoters and in untranslated regions of mRNAs. Further, we modify the turbidostat
platform to enable ramped selections, allowing feedback on temperature or drug concentration to optimize
selections. In the third aim, we design new proteins that bind to a protein-protein interface and disrupt an
interaction. These inhibitory proteins will allow us to assess the roles of individual members of large protein
families that are difficult to analyze. Finally, in the fourth aim, we generate new biosensors to detect the levels
of a small molecule and of a protein produced in yeast.

## Key facts

- **NIH application ID:** 10141248
- **Project number:** 5P41GM103533-25
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** STANLEY FIELDS
- **Activity code:** P41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $312,823
- **Award type:** 5
- **Project period:** 1997-09-30 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10141248

## Citation

> US National Institutes of Health, RePORTER application 10141248, Perturbing and Sensing Changes to Complex Pathways (5P41GM103533-25). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10141248. Licensed CC0.

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