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Integrative Approaches for Probing Cell Mechanotransduction in Health and Disease

Award Number: R35GM128859
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: 08/23/2018
PERIOD OF PERFORMANCE END DATE: 07/31/2024

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Integrative Approaches for Probing Cell Mechanotransduction in Health and Disease - Project Summary Notch receptors are mechanically activated transmembrane proteins that play important roles in regulating cell fate, differentiation, proliferation, adhesion, and many other critical processes. However, the majority of studies to date have been focused largely on understanding Notch from biochemical and genetic perspectives, and only recently been explored as a mechanoreceptor. Given the varied roles Notch plays in both normal and pathological states, it is necessary to formulate an integrated mechano-chemical perspective of Notch signaling and regulation as such outlook is required to achieve a comprehensive view of this critical pathway. In this project, my lab will leverage our expertise in chemical probe development and molecular tool design in order to address sharply focused mechanistic questions regarding Notch mechanotransduction. In order to distinguish our contributions from those of others, we will pursue a multi-scale understanding of the pathway by combining single molecule studies and high-resolution imaging with the aim of understanding how the activation of the receptor is coupled to biomechanical events that occur within the cell. In particular, new correlative light and electron microscopy will be developed and applied to determine the precise timing and location of events surrounding Notch signal transduction. In addition, in order to address important questions regarding the source and magnitude of the external forces that are experienced by cells, we will also create synthetic versions of Notch and apply them as genetically encoded “tensiometers.” Successful execution of this work will provide deep insights into the synergy occurring between biochemical and mechanical cues as well as increase our overall understanding of the how cells sense and interpret mechanical information.


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 = $449,625 )
2025	2025	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Biomedical Research and Research Training	000	6	12/24/2024	COMPETING CONTINUATION	$449,625
2025	2022	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Biomedical Research and Research Training	001	5	3/13/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $449,625

Issue Date FY: 2022 ( Subtotal = $412,500 )
2022	2022	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Biomedical Research and Research Training	000	5	8/25/2022	NON-COMPETING CONTINUATION	$412,500
														Subtotal = $412,500

Issue Date FY: 2021 ( Subtotal = $753,406 )
2021	2021	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Biomedical Research and Research Training	001	4	7/26/2021	NON-COMPETING CONTINUATION	$412,500
2021	2021	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Biomedical Research and Research Training	000	3	6/18/2021	SUPPLEMENT FOR EXPANSION	$340,906
														Subtotal = $753,406

Issue Date FY: 2020 ( Subtotal = $412,500 )
2020	2020	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Biomedical Research and Research Training	000	3	8/18/2020	NON-COMPETING CONTINUATION	$412,500
														Subtotal = $412,500

Issue Date FY: 2019 ( Subtotal = $412,500 )
2019	2019	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Biomedical Research and Research Training	000	2	8/8/2019	NON-COMPETING CONTINUATION	$412,500
														Subtotal = $412,500

Issue Date FY: 2018 ( Subtotal = $412,500 )
2018	2018	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Biomedical Research and Research Training	000	1	8/23/2018	NEW	$412,500
														Subtotal = $412,500

Grand Total All Awards = $2,853,031

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Integrative Approaches for Probing Cell Mechanotransduction in Health and Disease

Award Number: R35GM128859

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: 08/23/2018

PERIOD OF PERFORMANCE END DATE: 07/31/2024

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