# Directed Evolution of Cell-Type Specific On-Demand Signaling Control Systems

> **NIH NIH DP2** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2021 · $1,339,489

## Abstract

Project Summary/Abstract
This project will expand my recent inventions in directed evolution to create tools for cell-type specific
photoswitchable tuning of G-protein coupled receptors. The human genome encodes >900 G-protein
coupled receptors (GPCRs). Found in every cell, GPCRs contribute to every known biological process;
from our sense of taste, smell, and sight to coordinating hormone, neurotransmitter, and immune
functions. The past one-hundred years of biochemical research on this protein family has produced
346 structural determinations, >100,000 confirmed ligands, and a wealth of signaling assay
platforms. Absent from this impressive roster are any tools for the discrete, cell-type specific tuning
of endogenous receptor activity (Fig 1). Without such tools, we lack the ability to directly connect
discrete GPCR signaling events to cell-type specific physiological outputs. Such tools are essential if
we are to understand how GPCRs dictate human health and disease. In this NIH New Innovator
proposal, I will expand my recently invented platform for mammalian directed evolution to create a
production pipeline for cell-type specific, photoswitchable allosteric modulators of GPCRs. I will then
develop the first of these modulators for the D1 and D2 dopamine GPCRs and use these tools to refine
existing models of dopaminergic reward signaling in the murine brain. The success of this proposal
will benefit every field of biomedical research, creating a pipeline to gain tunable control of not only
any GPCR, but any cell signaling protein.

## Key facts

- **NIH application ID:** 10246098
- **Project number:** 1DP2GM146247-01
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Justin G. English
- **Activity code:** DP2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,339,489
- **Award type:** 1
- **Project period:** 2021-09-23 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10246098

## Citation

> US National Institutes of Health, RePORTER application 10246098, Directed Evolution of Cell-Type Specific On-Demand Signaling Control Systems (1DP2GM146247-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10246098. Licensed CC0.

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