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Investigating mechanisms of coordinating actinstructure across multiple levels oforder

Award Number: F32GM154448
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 06/01/2024
PERIOD OF PERFORMANCE END DATE: 02/10/2028

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Investigating mechanisms of coordinating actinstructure across multiple levels oforder - PROJECT SUMMARY: An organism's capacity to develop and grow is heavily dependent on its ability to organize various aspects of structure, ranging from G-actin to F-actin, cross-linked filaments, F-actin networks, and multicellular networks—in short, coordinate structure at multiple levels of order. Despite advances in characterizing proteins that affect actin at different levels of the structural hierarchy, we have limited knowledge of how regulation of actin is integrated across these hierarchical levels. Bitesize, the only Synaptotagmin-like protein in flies, is a membrane-bound protein that has recently been demonstrated to also directly bundle filamentous actin; preliminary data has further demonstrated that Bitesize promotes F-actin assembly. However, the mechanisms driving these actin-organizing behaviors of Bitesize have not been determined; moreover, the manner in which such mechanisms combine to produce a net effect in vivo is unknown. The long-term goal of this work is to elucidate how mechanisms that control different hierarchical levels of actin organization are integrated to facilitate morphogenesis. The overall objective of this proposal is to determine the mechanisms underlying Bitesize's organization of actin and their combined effect on Drosophila embryo development. My rationale for the proposed work is that Bitesize demonstrates direct interaction with actin, and therefore offers a unique opportunity to study the direct regulation of actin's structural hierarchy at multiples levels through the probing of a single protein. My hypothesis is that Bitesize integrates the regulation of actin assembly and actin bundling via distinct domains along its length. My aims are to: 1) determine the mechanism used by Bitesize to bundle actin, and 2) determine whether Bitesize separately regulates assembly and nucleation of actin. This approach is innovative in its coupling of structure-function analysis of Bitesize’s interaction partners with the in vivo study of btsz gene function in an animal tissue using precise gene edits. My proposed research is significant because it will determine means of coordinating hierarchical structures of actin, and because it is expected to demonstrate new mechanisms of regulating actin, such as stimulation of Dia via formin elongation effector domains, that have not been demonstrated in animals in vivo. This research will be accompanied by training in biochemistry as well as Drosophila embryology and genetics, which will take place in the Martin lab and Schwartz lab in the Department of Biology and Cryo-EM Facility at MIT, as well as in the Goode lab at Brandeis University. Together, this research and training will prepare me to establish an independent lab to investigate fundamental questions related to the formation of functional, hierarchical structures in cells and tissues.


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 = $81,040 )
2026	2026	MASSACHUSETTS INSTITUTE OF TECHNOLOGY	77 MASSACHUSETTS AVE	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Biomedical Research and Research Training	002	2	2/6/2026	NON-COMPETING CONTINUATION	$81,040
2026	2024	MASSACHUSETTS INSTITUTE OF TECHNOLOGY	77 MASSACHUSETTS AVE	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Biomedical Research and Research Training	000	1	11/25/2025	NEW	$0
2026	2024	MASSACHUSETTS INSTITUTE OF TECHNOLOGY	77 MASSACHUSETTS AVE	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Biomedical Research and Research Training	001	1	12/15/2025	NEW	$0
														Subtotal = $81,040

Issue Date FY: 2025 ( Subtotal = $0 )
2025	2024	MASSACHUSETTS INSTITUTE OF TECHNOLOGY	77 MASSACHUSETTS AVE	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Biomedical Research and Research Training	001	1	8/19/2025	NEW	$0
2025	2024	MASSACHUSETTS INSTITUTE OF TECHNOLOGY	77 MASSACHUSETTS AVE	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Biomedical Research and Research Training	000	1	5/21/2025	NEW	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $77,284 )
2024	2024	MASSACHUSETTS INSTITUTE OF TECHNOLOGY	77 MASSACHUSETTS AVE	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Biomedical Research and Research Training	000	1	5/24/2024	NEW	$77,284
2024	2024	MASSACHUSETTS INSTITUTE OF TECHNOLOGY	77 MASSACHUSETTS AVE	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Biomedical Research and Research Training	001	1	5/24/2024	NEW	$0
														Subtotal = $77,284

Grand Total All Awards = $158,324

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Investigating mechanisms of coordinating actinstructure across multiple levels oforder

Award Number: F32GM154448

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 06/01/2024

PERIOD OF PERFORMANCE END DATE: 02/10/2028

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