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Genetic regulatory mechanism in development and differentiation

Award Number: R35GM126975
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: 04/01/2018
PERIOD OF PERFORMANCE END DATE: 03/31/2024

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Genetic regulatory mechanism in development and differentiation - Project Summary/Abstract Determination of cellular identity is crucial in a variety of developmental frameworks. Fate specification typically involves an initial identity/pathway choice, which can be either deterministic or stochastic. Once selected this identity is reinforced and remembered using mechanisms that are often distinct from those deployed in the initial choice. Lastly, the chosen pathway must be faithfully executed so that cells differentiate appropriately. Over the years, we’ve investigated the process of cell fate specification in several distinct developmental contexts using the genetically tractable fruit fly, Drosophila melanogaster as our model system. Depending on the developmental pathway and the “step” in the specification process (e.g., pathway maintenance) the precise molecular mechanisms needed for proper specification can be at many different levels (cell-cell signaling, transcription, splicing, chromosome structure). In the first part of this proposal we examine the specification of primordial germ cells (PGCs) in the early embryo. In mammals PGC specification depends upon inductive BMP and Wnt signals. In contrast, in multicellular animals other than mammals, PGC specification has long been thought to be a cell-autonomous process that depends upon maternally deposited factors. However, we have recently discovered that BMP signals from somatic cells play an important role in PGC specification in the fly. This discovery suggests that the process of PGC specification across the animal kingdom may be much more similar than previously believed. Our proposed experiments are directed towards understanding the functional coordination between the cell autonomous factors and the BMP pathway during acquisition and maintenance of PGC identity. The second part of the proposal is focused on chromosome architectural elements (boundary elements, Polycomb Response Elements and Chromatin Entry Sites). The proposed experiments will examine how these elements function to determine the topological organization of eukaryotic chromosomes. We will also explore how the activities of these elements impact pathway initiation, memory and execution in several distinct developmental pathways.


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: 2024 ( Subtotal = -$12 )
2024	2022	THE TRUSTEES OF PRINCETON UNIVERSITY	1 NASSAU HALL	PRINCETON	NJ	08544	MERCER	USA	Biomedical Research and Research Training	000	5	9/24/2024	NON-COMPETING CONTINUATION	-$12
														Subtotal = -$12

Issue Date FY: 2022 ( Subtotal = $621,104 )
2022	2022	TRUSTEES OF PRINCETON UNIVERSITY, THE	1 NASSAU HALL	PRINCETON	NJ	08544	MERCER	USA	Biomedical Research and Research Training	000	5	3/22/2022	NON-COMPETING CONTINUATION	$558,990
2022	2022	TRUSTEES OF PRINCETON UNIVERSITY, THE	1 NASSAU HALL	PRINCETON	NJ	08544	MERCER	USA	Biomedical Research and Research Training	001	5	7/19/2022	NON-COMPETING CONTINUATION	$62,114
														Subtotal = $621,104

Issue Date FY: 2021 ( Subtotal = $621,104 )
2021	2021	TRUSTEES OF PRINCETON UNIVERSITY, THE	1 NASSAU HALL	PRINCETON	NJ	08544	MERCER	USA	Biomedical Research and Research Training	000	4	3/29/2021	NON-COMPETING CONTINUATION	$621,104
														Subtotal = $621,104

Issue Date FY: 2020 ( Subtotal = $621,104 )
2020	2020	TRUSTEES OF PRINCETON UNIVERSITY, THE	1 NASSAU HALL	PRINCETON	NJ	08544	MERCER	USA	Biomedical Research and Research Training	000	3	3/27/2020	NON-COMPETING CONTINUATION	$621,104
														Subtotal = $621,104

Issue Date FY: 2019 ( Subtotal = $621,104 )
2019	2019	TRUSTEES OF PRINCETON UNIVERSITY, THE	1 NASSAU HALL	PRINCETON	NJ	08544	MERCER	USA	Biomedical Research and Research Training	000	2	3/27/2019	NON-COMPETING CONTINUATION	$621,104
														Subtotal = $621,104

Issue Date FY: 2018 ( Subtotal = $520,848 )
2018	2018	TRUSTEES OF PRINCETON UNIVERSITY, THE	1 NASSAU HALL	PRINCETON	NJ	08544	MERCER	USA	Biomedical Research and Research Training	000	1	3/23/2018	NEW	$520,848
														Subtotal = $520,848

Grand Total All Awards = $3,005,252

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Genetic regulatory mechanism in development and differentiation

Award Number: R35GM126975

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: 04/01/2018

PERIOD OF PERFORMANCE END DATE: 03/31/2024

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