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Deconstructing and recapitulating the genetic basis of gene regulatory network redeployment

Award Number: R00GM147343
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/07/2022
PERIOD OF PERFORMANCE END DATE: 07/31/2028

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Deconstructing and recapitulating the genetic basis of gene regulatory network redeployment - 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.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $247,693 )
2025	2025	KANSAS STATE UNIVERSITY	1601 VATTIER STREET	MANHATTAN	KS	66506	RILEY	USA	Biomedical Research and Research Training	000	3	8/11/2025	EXTENSION WITH OR WITHOUT FUNDS	$247,693
														Subtotal = $247,693

Grand Total All Awards = $247,693

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Deconstructing and recapitulating the genetic basis of gene regulatory network redeployment

Award Number: R00GM147343

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/07/2022

PERIOD OF PERFORMANCE END DATE: 07/31/2028

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