Thursday, November 21, 2024 11/21/2024

Unraveling heterogeneity of molecular mechanisms in cellular motility and morphodynamics by machine learning

Award Number: R35GM133725
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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PROJECT SUMMARY/ABSTRACT Live cell imaging has revolutionized the study of dynamic cellular processes, enabling researchers to gain valuable functional insights that would be impossible to obtain from static images. The recent advances in microscopy technology have made it possible to acquire an unprecedented amount of live cell image data at high spatiotemporal resolutions. However, this abundance of data has brought new challenges, particularly concerning phenotypic and causal heterogeneity. This heterogeneity can complicate the analysis and interpretation of the data, making it challenging to identify critical mechanistic details and understand how cellular processes function in different conditions. To address this issue, we have been developing machine learning platforms that can deconvolve the heterogeneity of live cell images at subcellular and cellular levels. However, there are still many challenges in analyzing live cell heterogeneity in greater detail. First, conventional feature selection/learning that aids in classifying known phenotypes could eliminate biologically meaningful heterogeneity. Second, current cell biology research focuses primarily on mechanisms that produce similar average effects across various populations, which could suffer from causal heterogeneity. Even with the significant progress made in single-cell biology, the discovery of causal mechanisms at the single-cell resolution is still not fully achieved. Finally, the substantial heterogeneity in cell motility and morphodynamics poses a challenge to obtaining integrated and systematic understandings of these processes, despite their clear significance in fields such as tissue regeneration and cancer metastasis. To overcome these challenges, we propose to advance current machine learning methods to i) identify features that preserve subtype heterogeneity while being discriminative between known phenotypes, ii) acquire causal datasets of live cell images by tracking cells before and after optogenetic treatment, and iii) deconvolve the causal heterogeneity of single live cells by integrating time-series modeling and deep learning. We will apply these methods to map out single-cell mechanisms governing cellular motility and morphodynamics of various cell types, which will be valuable resources for the cell biology community. Then, we will characterize how mechanical and metabolic perturbations can shape the heterogeneous landscapes of cell motility and morphodynamics, providing new insights into the underlying mechanisms integrating these processes.


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 = $0 )
2025	2024	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Biomedical Research and Research Training	000	7	11/5/2024	COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $452,217 )
2024	2024	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Biomedical Research and Research Training	000	7	9/11/2024	COMPETING CONTINUATION	$452,217
														Subtotal = $452,217

Issue Date FY: 2023 ( Subtotal = $442,500 )
2023	2023	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Biomedical Research and Research Training	000	6	9/8/2023	NON-COMPETING CONTINUATION	$442,500
														Subtotal = $442,500

Issue Date FY: 2022 ( Subtotal = $618,001 )
2022	2022	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Biomedical Research and Research Training	000	5	9/19/2022	NON-COMPETING CONTINUATION	$442,500
2022	2022	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Biomedical Research and Research Training	001	5	9/20/2022	SUPPLEMENT FOR EXPANSION	$175,501
														Subtotal = $618,001

Issue Date FY: 2021 ( Subtotal = $826,715 )
2021	2021	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Biomedical Research and Research Training	004	4	8/23/2021	NON-COMPETING CONTINUATION	$442,500
2021	2021	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Biomedical Research and Research Training	005	4	9/20/2021	SUPPLEMENT FOR EXPANSION	$318,600
2021	2020	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Biomedical Research and Research Training	001	3	1/12/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$442,500
2021	2020	WORCESTER POLYTECHNIC INSTITUTE	100 INSTITUTE RD	WORCESTER	MA	01609	WORCESTER	USA	Biomedical Research and Research Training	000	2	1/11/2021	NON-COMPETING CONTINUATION	-$376,885
2021	2020	CHILDREN'S HOSPITAL CORPORATION, THE	300 LONGWOOD AVE	BOSTON	MA	02115	SUFFOLK	USA	Biomedical Research and Research Training	003	3	7/11/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$9,924
2021	2019	WORCESTER POLYTECHNIC INSTITUTE	100 INSTITUTE RD	WORCESTER	MA	01609	WORCESTER	USA	Biomedical Research and Research Training	002	1	7/11/2021	NEW	-$9,924
														Subtotal = $826,715

Issue Date FY: 2020 ( Subtotal = $376,885 )
2020	2020	WORCESTER POLYTECHNIC INSTITUTE	100 INSTITUTE RD	WORCESTER	MA	01609	WORCESTER	USA	Biomedical Research and Research Training	000	2	9/21/2020	NON-COMPETING CONTINUATION	$376,885
														Subtotal = $376,885

Issue Date FY: 2019 ( Subtotal = $232,688 )
2019	2019	WORCESTER POLYTECHNIC INSTITUTE	100 INSTITUTE RD	WORCESTER	MA	01609	WORCESTER	USA	Biomedical Research and Research Training	000	1	8/29/2019	NEW	$232,688
														Subtotal = $232,688

Grand Total All Awards = $2,949,006

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Unraveling heterogeneity of molecular mechanisms in cellular motility and morphodynamics by machine learning

Award Number: R35GM133725

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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