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Mathematical modeling of mechanical and spatiotemporal processes in cellular functions

Award Number: R35GM138370
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: 09/01/2020
PERIOD OF PERFORMANCE END DATE: 02/28/2031

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Mathematical modeling of mechanical and spatiotemporal processes in cellular functions - Project Summary The PI’s laboratory focuses on mathematical modeling of mechanical and spatiotemporal processes in cellular functions. Experiment data on these processes tend to be fragmented, as it remains challenging to simultaneously track the mechanical and spatiotemporal dynamics of multiple molecular species involved in complex cellular mechanisms. Mathematical modeling offers a powerful tool to integrate heterogeneous data with basic laws of physics and chemistry, propose coherent mechanistic frameworks, and guide new experiments. Due to many strong physical constraints, modeling the mechanical and spatiotemporal dynamics often suffers less uncertainty, a common issue in biological modeling. Consequently, such models can provide a central framework to which additional biological details can be gradually added. The PI’s research focuses on two broad biological areas: mitosis and bacterial motility. In mitosis, the PI’s works have brought unique insights into how mechanical and spatiotemporal dynamics of structural and signaling components contribute to proper mitotic spindle assembly and faithful chromosome segregation, and how cells cope with aberrancies in key spindle components, such as centrosome amplification. In bacterial motility, the PI’s works have brought novel mechanistic understanding to force generation and motility regulation in various bacterial motility mechanisms. Over the next five years, the PI’s lab will leverage various modeling techniques to address key gaps of knowledge in two focal topics: multicentrosomal mitosis and growing chain–mediated bacterial sliding motility. Multicentrosomal mitosis has strong implications in cancer as centrosome amplification is prevalent in cancer development. Anti-cancer therapies targeting multicentrosomal mitosis have long been proposed, but with yet limited success. The PI’s research aims to elucidate the mechanism and outcome of single multicentrosomal mitosis through agent-based modeling of multicentrosomal spindle assembly, and the role of multicentrosomal mitosis in cancer development and treatment through stochastic clonal evolution modeling. Growing chain–mediated bacterial sliding motility, a growth-driven motility mechanism enabled by long chains of end-to-end connected cells, could contribute to fast host tissue penetration by Clostridium perfringens and spreading of other chain-forming bacteria. The PI’s previous model revealed a mechanical limitation of this sliding motility. The proposed study will interrogate the mechanism and role of persistent chain-chain interactions that are commonly observed but not understood, as well as exploiting hyperelastic and morphodynamic finite-element modeling to incorporate nonlinear mechanical properties of the cell into more realistic models for the growing bacterial chain. The PI’s research will generate new knowledge and predictive tools to facilitate future health-related innovations in cancer treatment and bacterial control.


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: 2026 ( Subtotal = $422,510 )
2026	2026	VIRGINIA POLYTECHNIC INSTITUTE & STATE UNIVERSITY	300 TURNER ST NW	BLACKSBURG	VA	24060	MONTGOMERY	USA	Biomedical Research and Research Training	001	6	2/20/2026	COMPETING CONTINUATION	$422,510
2026	2024	VIRGINIA POLYTECHNIC INSTITUTE & STATE UNIVERSITY	300 TURNER ST NW	BLACKSBURG	VA	24060	MONTGOMERY	USA	Biomedical Research and Research Training	000	5	2/20/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $422,510

Issue Date FY: 2025 ( Subtotal = $0 )
2025	2024	VIRGINIA POLYTECHNIC INSTITUTE & STATE UNIVERSITY	300 TURNER ST NW	BLACKSBURG	VA	24060	MONTGOMERY	USA	Biomedical Research and Research Training	000	5	8/11/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $86,000 )
2024	2024	VIRGINIA POLYTECHNIC INSTITUTE & STATE UNIVERSITY	300 TURNER ST NW	BLACKSBURG	VA	24060	MONTGOMERY	USA	Biomedical Research and Research Training	000	5	9/11/2024	NON-COMPETING CONTINUATION	$86,000
														Subtotal = $86,000

Issue Date FY: 2023 ( Subtotal = $372,630 )
2023	2023	VIRGINIA POLYTECHNIC INSTITUTE & STATE UNIVERSITY	300 TURNER ST NW	BLACKSBURG	VA	24060	MONTGOMERY	USA	Biomedical Research and Research Training	000	4	9/8/2023	NON-COMPETING CONTINUATION	$372,630
														Subtotal = $372,630

Issue Date FY: 2022 ( Subtotal = $371,720 )
2022	2022	VIRGINIA POLYTECHNIC INSTITUTE & STATE UNIVERSITY	300 TURNER ST NW	BLACKSBURG	VA	24060	MONTGOMERY	USA	Biomedical Research and Research Training	001	3	9/1/2022	NON-COMPETING CONTINUATION	$371,720
2022	2021	VIRGINIA POLYTECHNIC INSTITUTE AND STATE UNIVERSITY	300 TURNER ST NW STE 4200	BLACKSBURG	VA	24061	MONTGOMERY	USA	Biomedical Research and Research Training	000	2	11/5/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $371,720

Issue Date FY: 2021 ( Subtotal = $370,837 )
2021	2021	VIRGINIA POLYTECHNIC INSTITUTE AND STATE UNIVERSITY	300 TURNER ST NW STE 4200	BLACKSBURG	VA	24061	MONTGOMERY	USA	Biomedical Research and Research Training	000	2	8/18/2021	NON-COMPETING CONTINUATION	$370,837
														Subtotal = $370,837

Issue Date FY: 2020 ( Subtotal = $373,180 )
2020	2020	VIRGINIA POLYTECHNIC INSTITUTE & STATE UNIVERSITY	300 TURNER ST NW STE 4200	BLACKSBURG	VA	24061	MONTGOMERY	USA	Biomedical Research and Research Training	000	1	8/12/2020	NEW	$373,180
														Subtotal = $373,180

Grand Total All Awards = $1,996,877

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Mathematical modeling of mechanical and spatiotemporal processes in cellular functions

Award Number: R35GM138370

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: 09/01/2020

PERIOD OF PERFORMANCE END DATE: 02/28/2031

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