# Deconstructing and recapitulating the genetic basis of gene regulatory network redeployment

> **NIH NIH K99** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2022 · $100,000

## Abstract

PROJECT SUMMARY
 The goal of the proposed research is to understand how gene regulatory networks (GRNs) are modified
to generate structures repeated throughout the body. GRNs organize the activation of hundreds of genes
under the control of one or few transcription factors or signaling molecules. The activation of specific GRNs
designate cell type. The reuse of a GRN in different tissues of the body is thought to generate repeated body
parts such as hair, muscles, or neurons. This is generally hypothesized to proceed by the redeployment of
factors situated high within the GRN to a new context. Despite much effort to identify the mutations that lead to
GRN redeployment, it has remained elusive. The proposed research will identify the genetic changes that led
to the redeployment of a GRN that has been extensively characterized and manipulated in Drosophila.
 Furthermore, I will investigate how the architecture of a GRN can be modified in a tissue-specific
fashion. Most studies have focused only on the upstream factors that control GRNs, but I will use genomic
techniques to investigate how downstream genes in the network are activated by and connected to their
upstream transcription factors. I will determine if the same regulatory elements and direct binding sites are
reused in all tissues or if they vary between tissues. This proposal will use cutting edge transgenic techniques
to not only describe associations but test predictions through genetic manipulation. I will determine which
genetic changes are necessary and sufficient for the redeployment and modification of a GRN. The ultimate
goal will be to edit the genome to redeploy a GRN into a naive background.
 The proposed work will generate one of the most complete models a GRN’s redeployment across
tissues. This model can help us understand what genetic changes may move a GRN into a new tissue and
whether the full GRN will be redeployed in the new context. Human health conditions with large phenotypic
effects such as birth defects have been traced back to mutations in regulatory elements of upstream factors
which lead to ectopic expression and the generation of repeated structures in new locations. The proposed
work will establish a general model for causes of ectopic expression, providing general insights into the
architecture of GRNs governing repeated structures in a variety of systems.

## Key facts

- **NIH application ID:** 10506582
- **Project number:** 1K99GM147343-01
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Gavin Ryan Rice
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $100,000
- **Award type:** 1
- **Project period:** 2022-09-07 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10506582

## Citation

> US National Institutes of Health, RePORTER application 10506582, Deconstructing and recapitulating the genetic basis of gene regulatory network redeployment (1K99GM147343-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10506582. Licensed CC0.

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