# Programmable evolution of optogenetic systems

> **NIH NIH R21** · STANFORD UNIVERSITY · 2021 · $236,100

## Abstract

Project Summary: The ability to use light to control biological processes has enabled the careful
dissection of biology and could be developed into future treatments for blindness, cancer, and many
other diseases. Systems that respond to red to near-infrared (NIR) light are particularly useful because
those wavelengths efficiently penetrate tissue, but these systems can be greatly improved by
engineering them to efficiently bind endogenous chromophores or to be more sensitive to light. By
using a new continuous evolution system, OrthoRep, we will evolve the Phytochrome B (PhyB)
optogenetic tool to use biliverdin (which is present in every cell) as a chromophore and evolve versions
that are activated by different wavelengths of NIR light. This will be accomplished by modifying the
Automated Continuous Evolution (ACE) that can automatically apply evolutionary pressure as the gene
of the optogenetic tool continuously mutates. Because PhyB will respond to light by activating a gene
essential for survival, it will be possible to evolve the activation wavelength, the amount of light that is
required to activate the gene, and the level of the activation once illuminated. Evolved PhyB mutants
that have useful properties will be validated/characterized biochemically and for controlling genes in
mammalian cells. The resulting optogenetic tools will enable new opportunities for in vivo optogenetics
and the modified ACE can be used to develop many other types of optogenetic tools, optical sensors,
and more.

## Key facts

- **NIH application ID:** 10318056
- **Project number:** 1R21GM143806-01
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Todd P Coleman
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $236,100
- **Award type:** 1
- **Project period:** 2021-09-15 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10318056

## Citation

> US National Institutes of Health, RePORTER application 10318056, Programmable evolution of optogenetic systems (1R21GM143806-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10318056. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*