Wednesday, May 8, 2024 5/8/2024

Single-cell Metabolomics and Proteomics: The Missing Link to Understanding Vertebrate Embryonic Patterning

Award Number: R35GM124755
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Abstract Understanding embryonic development requires knowledge of all the molecules produced as the zygote differentiates into the three primary germ layers of the embryo. Four decades of innovative embryological manipulations, testing of gene functions one gene at a time, and recently, Next-Generation Sequencing have identified multiple transcripts and abundant proteins that are essential to the patterning of the vertebrate embryo. However, very little is known about the total array of proteins and their post-translational modifications that contribute to the formation of the germ layers, and next to nothing is known about the contribution of small molecules (called metabolites) to these processes. To date, systems biology has defined the spatial and temporal changes of mRNAs, abundant proteins, and metabolites in the whole embryo, but it has been technologically impossible to utilize high-resolution mass spectrometry (HRMS), the gold standard technology for small molecules, to study hundreds-to-thousands of metabolites and proteins in single embryonic cells in the vertebrate embryo. The proposed research program fills this enormous knowledge and technological gap by utilizing novel single-cell mass spectrometry technologies to understand cell molecular processes that contribute to the formation of the three germ layers required for the successful patterning of the vertebrate frog (Xenopus laevis) embryo, a favorite model in cell/developmental biology. Most recently, single-cell mass spectrometry discovered metabolites capable of altering the normal cell fates of embryonic cells, suggesting that the complete molecular players are not yet fully identified or understood for germ layer induction. The proposed research program will determine this missing link in the understanding of molecular mechanisms governing vertebrate development. This work will integrate quantitative single-cell mass spectrometry, cell fate tracking, and gene knock-down experiments to determine how a targeted set of small-molecular reactions impact the formation of signaling centers required for dorsal axis specification. The outcomes of this interdisciplinary approach will help illuminate the role of the proteome and metabolome for the establishment of these important precursors. Because these molecular processes are highly conserved across vertebrates, the data collected from Xenopus are likely to have high relevance to human structural birth defects. The new biochemical information that will be obtained in individual embryonic cells and their progeny (cell lineage) at several critical developmental time points will also advance other research fields that involve cell differentiation (e.g., of stem cells) and the developmental origins of adult disease.


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 = $437,836 )
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
														Subtotal = $437,836

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	002	5	8/27/2020	SUPPLEMENT FOR EXPANSION	$72,156
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
														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	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	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	003	2	6/21/2018	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$1
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
														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 = $2,565,701

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Single-cell Metabolomics and Proteomics: The Missing Link to Understanding Vertebrate Embryonic Patterning

Award Number: R35GM124755

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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