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Sub-Cellular Mass Spectrometry Discoveries: Metabolic Encoding of the Embryonic Body Plan

Award Number: R35GM124755
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: 09/01/2017
PERIOD OF PERFORMANCE END DATE: 01/31/2029

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Sub-Cellular Mass Spectrometry Discoveries: Metabolic Encoding of the Embryonic Body Plan - Abstract A critical process for early development of the vertebrate embryo is induction of the three primary germ layers. Knowledge of the molecules that are produced in each embryonic cell is essential to understanding their function to pattern the embryonic body. Decades of innovative cell biological and embryological studies, assessment of function one gene at a time, and recently deep transcriptomics profiling via next-generation sequencing have exposed the developmental roles of important genes, transcripts, and some proteins. As a result, scientists have defined the spatial and temporal changes of mRNAs and abundant proteins, and some serendipitously identified metabolites of importance, such as folate assisting in closure of the neural tube. However, it has been technologically impossible to utilize high-resolution mass spectrometry (HRMS), the gold standard technology for proteomics and metabolomics (`omics), to study hundreds of metabolites and thousands proteins in single embryonic cells in the vertebrate embryo. Further, in developing systems, a complex correlation between gene transcription and translation as well as posttranslational modifications complicate the use of mRNA information to approximate protein and metabolite levels. Without the availability of single-cell HRMS as a routine laboratory tool or other technologies capable of deep metabolomics and proteomics, scientists at present lack insights into metabolic processes that contribute to early embryonic patterning. The research program proposed here fills this enormous knowledge and technological gap by utilizing ultrahigh-sensitivity HRMS platforms that were custom-designed, custom-built, and validated in the vertebrate frog (Xenopus laevis) embryo, a popular model in cell/developmental biology, to understand noncanonical metabolomic processes that control formation of the germ layers. Most recently, single-cell HRMS in X. laevis has discovered metabolites that are capable of (i) altering the normal cell fates of embryonic cells, (ii) communicating between blastomeres, and (iii) affecting the whole-organismal performance of the resulting tadpole. These findings have shed light on a gap in our basic knowledge of molecules participating in the successful induction of the germ layers. This research program will determine roles that metabolites play in patterning the embryonic body plan. This work will integrate classical embryological manipulations, cell-fate tracking, and fluorescent microscopy with new-generation quantitative mass spectrometry capable of subcellular sensitivity to characterize how targeted metabolic reactions impact reproducible tissue fates in the X. laevis embryo. Because these molecular processes are highly conserved across vertebrates, the data collected from Xenopus are likely to have high relevance to human development. This interdisciplinary research program will help discover metabolic mechanisms governing cell differentiation and embryogenesis.


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 = $470,460 )
2025	2025	UNIVERSITY OF MARYLAND, COLLEGE PARK	3112 LEE BUILDING	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Biomedical Research and Research Training	002	8	12/24/2024	NON-COMPETING CONTINUATION	$374,798
2025	2025	UNIVERSITY OF MARYLAND, COLLEGE PARK	3112 LEE BUILDING	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Biomedical Research and Research Training	003	8	12/26/2024	SUPPLEMENT FOR EXPANSION	$81,995
2025	2025	UNIVERSITY OF MARYLAND, COLLEGE PARK	3112 LEE BUILDING	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Biomedical Research and Research Training	001	7	11/21/2024	SUPPLEMENT FOR EXPANSION	$13,667
2025	2024	UNIVERSITY OF MARYLAND, COLLEGE PARK	3112 LEE BUILDING	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Biomedical Research and Research Training	000	7	11/14/2024	COMPETING CONTINUATION	$0
														Subtotal = $470,460

Issue Date FY: 2024 ( Subtotal = $657,464 )
2024	2024	UNIVERSITY OF MARYLAND, COLLEGE PARK	3112 LEE BUILDING	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Biomedical Research and Research Training	002	7	6/13/2024	COMPETING CONTINUATION	$1
2024	2024	UNIVERSITY OF MARYLAND, COLLEGE PARK	3112 LEE BUILDING	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Biomedical Research and Research Training	003	7	8/20/2024	SUPPLEMENT FOR EXPANSION	$219,628
2024	2024	UNIVERSITY OF MARYLAND, COLLEGE PARK	3112 LEE BUILDING	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Biomedical Research and Research Training	000	7	3/29/2024	COMPETING CONTINUATION	$437,836
2024	2021	UNIVERSITY OF MARYLAND, COLLEGE PARK	3112 LEE BUILDING	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Biomedical Research and Research Training	001	6	6/13/2024	NON-COMPETING CONTINUATION	-$1
														Subtotal = $657,464

Issue Date FY: 2022 ( Subtotal = -$72,155 )
2022	2021	UNIVERSITY OF MARYLAND, COLLEGE PARK	3112 LEE BLDG 7809 REGENTS DR	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Biomedical Research and Research Training	000	6	5/24/2022	SUPPLEMENT FOR EXPANSION	-$72,155
														Subtotal = -$72,155

Issue Date FY: 2021 ( Subtotal = $438,504 )
2021	2021	UNIVERSITY OF MARYLAND, COLLEGE PARK	3112 LEE BLDG 7809 REGENTS DR	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Biomedical Research and Research Training	000	6	9/1/2021	NON-COMPETING CONTINUATION	$366,348
2021	2021	UNIVERSITY OF MARYLAND, COLLEGE PARK	3112 LEE BLDG 7809 REGENTS DR	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Biomedical Research and Research Training	001	6	9/10/2021	SUPPLEMENT FOR EXPANSION	$72,156
														Subtotal = $438,504

Issue Date FY: 2020 ( Subtotal = $485,715 )
2020	2020	UNIVERSITY OF MARYLAND, COLLEGE PARK	3112 LEE BLDG 7809 REGENTS DR	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Biomedical Research and Research Training	000	4	8/17/2020	SUPPLEMENT FOR EXPANSION	$44,784
2020	2020	UNIVERSITY OF MARYLAND, COLLEGE PARK	3112 LEE BLDG 7809 REGENTS DR	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Biomedical Research and Research Training	001	5	8/26/2020	NON-COMPETING CONTINUATION	$368,775
2020	2020	UNIVERSITY OF MARYLAND, COLLEGE PARK	3112 LEE BLDG 7809 REGENTS DR	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Biomedical Research and Research Training	002	5	8/27/2020	SUPPLEMENT FOR EXPANSION	$72,156
														Subtotal = $485,715

Issue Date FY: 2019 ( Subtotal = $527,255 )
2019	2019	UNIVERSITY OF MARYLAND	3112 LEE BLDG 7809 REGENTS DR	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Biomedical Research and Research Training	000	3	7/15/2019	SUPPLEMENT FOR EXPANSION	$158,480
2019	2019	UNIVERSITY OF MARYLAND	3112 LEE BLDG 7809 REGENTS DR	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Biomedical Research and Research Training	001	4	8/22/2019	NON-COMPETING CONTINUATION	$368,775
														Subtotal = $527,255

Issue Date FY: 2018 ( Subtotal = $379,405 )
2018	2018	UNIVERSITY OF MARYLAND	3112 LEE BLDG 7809 REGENTS DR	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Biomedical Research and Research Training	004	3	8/31/2018	NON-COMPETING CONTINUATION	$371,725
2018	2017	THE GEORGE WASHINGTON UNIVERSITY	2121 I ST NW STE 601	WASHINGTON	DC	20052	DISTRICT OF COLUMBIA	USA	Biomedical Research and Research Training	002	1	6/21/2018	NEW	-$1
2018	2017	UNIVERSITY OF MARYLAND	3112 LEE BLDG 7809 REGENTS DR	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Biomedical Research and Research Training	001	2	6/7/2018	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$368,902
2018	2017	THE GEORGE WASHINGTON UNIVERSITY	2121 I ST NW STE 601	WASHINGTON	DC	20052	DISTRICT OF COLUMBIA	USA	Biomedical Research and Research Training	000	1	6/6/2018	NEW	-$361,222
2018	2017	UNIVERSITY OF MARYLAND	3112 LEE BLDG 7809 REGENTS DR	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Biomedical Research and Research Training	003	2	6/21/2018	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$1
														Subtotal = $379,405

Issue Date FY: 2017 ( Subtotal = $369,141 )
2017	2017	THE GEORGE WASHINGTON UNIVERSITY	2121 I ST NW STE 601	WASHINGTON	DC	20052	DISTRICT OF COLUMBIA	USA	Biomedical Research and Research Training	000	1	8/17/2017	NEW	$369,141
														Subtotal = $369,141

Grand Total All Awards = $3,255,789

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Sub-Cellular Mass Spectrometry Discoveries: Metabolic Encoding of the Embryonic Body Plan

Award Number: R35GM124755

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: 09/01/2017

PERIOD OF PERFORMANCE END DATE: 01/31/2029

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