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DMS/NIGMS 1: Multiscale modeling of Notch signaling during long-range lateral inhibition

Award Number: R01GM152810
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: 09/25/2023
PERIOD OF PERFORMANCE END DATE: 08/31/2026

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DMS/NIGMS 1: Multiscale modeling of Notch signaling during long-range lateral inhibition - The spatiotemporal distribution of morphogens contributes to the organized development of tissues and organs. One model of morphogen distribution is active transport, which includes cell based mechanisms like signaling filopodia. Signaling filopodia facilitate contact between distant cells in order to allow signaling to occur, and support several cell signaling paradigms during development. The proposed project will use multi-scale modeling and biological experiments to test the hypothesis that Notch signaling occurs via filopodia-filopodia mediated cell-cell contacts in vivo. This hypothesis will be tested in three objectives. (1) Investigate the mechanism of Notch activation on filopodia. A mechanical model of distinct modes of filopodia interactions will be used to quantify the forces generated during filopodia mediated signaling to identify the most likely mechanism for Notch activation. (2) Determine how Notch signal is relayed to the cell body. A mathematical model of filopodia in the presence of diffusion and active transport of signals will be developed to quantify the relative importance of each mechanism. We will support our model with genetic approaches and quantitative live imaging. (3) Create a multi-scale vertex model of Notch signaling during bristle cell patterning. We will combine the above molecular and cellular submodels of Notch signaling to create a truly multi-scale vertex model of the patterning thorax. This framework will support an in silico, real-time investigation of patterning dynamics via signaling filopodia to identify potential molecular regulators of this process. The success of this proposal will result in a foundational understanding of the mechanisms that drive long-range lateral inhibition during tissue patterning. We will introduce the first multi-scale mechanical model of the fly thorax that allows for cell-driven dynamics of filopodia and real-time activation of Notch. The experimental work proposed here addresses a major gap in our understanding of tissue development and homeostasis: how active cell processes contribute to the distribution and activation of signals.


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 = $194,584 )
2025	2025	CLARKSON UNIVERSITY	8 CLARKSON AVE	POTSDAM	NY	13676	SAINT LAWRENCE	USA	Biomedical Research and Research Training	000	3	8/13/2025	NON-COMPETING CONTINUATION	$194,584
														Subtotal = $194,584

Issue Date FY: 2024 ( Subtotal = $196,114 )
2024	2024	CLARKSON UNIVERSITY	8 CLARKSON AVE	POTSDAM	NY	13676	SAINT LAWRENCE	USA	Biomedical Research and Research Training	000	2	9/5/2024	NON-COMPETING CONTINUATION	$196,114
														Subtotal = $196,114

Issue Date FY: 2023 ( Subtotal = $198,008 )
2023	2023	CLARKSON UNIVERSITY	8 CLARKSON AVE	POTSDAM	NY	13676	SAINT LAWRENCE	USA	Biomedical Research and Research Training	000	1	9/20/2023	NEW	$198,008
														Subtotal = $198,008

Grand Total All Awards = $588,706

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DMS/NIGMS 1: Multiscale modeling of Notch signaling during long-range lateral inhibition

Award Number: R01GM152810

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: 09/25/2023

PERIOD OF PERFORMANCE END DATE: 08/31/2026

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