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From functional conservation to functional necessity of cis-regulatory modules

Award Number: R15GM135884
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: 09/16/2019
PERIOD OF PERFORMANCE END DATE: 06/30/2020

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From functional conservation to functional necessity of cis-regulatory modules - 1. PROJECT SUMMARY Our long-term research goal is to understand the function-evolution relationship in cis-regulatory modules (CRMs) such as enhancers and promoters. The main goal of this proposal is to test the hypothesis that CRMs with pleisiomorphic/ancestral activities represent essential CRMs for gene expression. This hypothesis focuses on conservation of molecular function to identify functionally important CRMs. Our preliminary quantitative analyses have shown the prevalence of CRMs that can drive reporter expression in distantly related species. Building upon the preliminary results and harnessing the power of our high-throughput methods for CRM analysis, this project will examine the necessity of CRMs with ancestral activities for expression of genes in sea urchin embryos. Aim 1 will identify CRMs with ancestral spatial activities by testing an unbiased set of 5,000 CRMs from the purple sea urchin, Strongylocentrotus purpuratus, in two distantly related echinoderms: the pencil urchin Eucidaris tribuloides and the sea star Patiria miniata. Because there is virtually no detectable sequence homology in non-coding regions between the purple urchin and the other species, trans-species CRM activities detected in this analysis are presumably ancestral. Aim 2 will examine the necessity of CRMs for gene expression in the purple urchin embryos by two complementary approaches: deletion of a select set of 30 CRMs by CRISPR, and massive perturbation of CRMs by knock-down of key regulatory genes. We will compare the results from Aim 1 and Aim 2 to test our central hypothesis. We will also test whether the observed prevalence of trans-species CRM activities is due to evolutionary constraints on CRMs and gene regulatory circuits. This project fulfills the goals of AREA program by primarily involving undergraduate and graduate students in research, specifically in functional and evolutionary analyses of CRMs that might be important for early embryonic development and related diseases. We anticipate that findings from this project can serve as an empirical foundation for rapidly identifying functionally important CRMs and related gene regulatory networks. This research may also lead to a general approach for using functional conservation rather than sequence conservation to study function-evolution relationships over almost any timescale without being limited by an inability to detect sequence homology.


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: 2022 ( Subtotal = -$364,615 )
2022	2019	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	303 COOPER ST	CAMDEN	NJ	08102	CAMDEN	USA	Biomedical Research and Research Training	000	1	5/17/2022	NEW	-$364,615
														Subtotal = -$364,615

Issue Date FY: 2021 ( Subtotal = $0 )
2021	2019	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	303 COOPER ST	CAMDEN	NJ	08102	CAMDEN	USA	Biomedical Research and Research Training	002	1	9/24/2021	NEW	$364,621
2021	2019	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	303 COOPER ST	CAMDEN	NJ	08102	CAMDEN	USA	Biomedical Research and Research Training	001	1	9/5/2021	NEW	-$364,621
2021	2019	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	303 COOPER ST	CAMDEN	NJ	08102	CAMDEN	USA	Biomedical Research and Research Training	000	1	8/12/2021	NEW	$0
														Subtotal = $0

Issue Date FY: 2019 ( Subtotal = $453,072 )
2019	2019	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	303 COOPER ST	CAMDEN	NJ	08102	CAMDEN	USA	Biomedical Research and Research Training	000	1	9/16/2019	NEW	$453,072
														Subtotal = $453,072

Grand Total All Awards = $88,457

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From functional conservation to functional necessity of cis-regulatory modules

Award Number: R15GM135884

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: 09/16/2019

PERIOD OF PERFORMANCE END DATE: 06/30/2020

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