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Role of Vesicular Trafficking Proteins in Regulating Centrosomes

Award Number: R15GM152965
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: 07/01/2024
PERIOD OF PERFORMANCE END DATE: 08/08/2024

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Role of Vesicular Trafficking Proteins in Regulating Centrosomes - Role of vesicular trafficking proteins in regulating centrosomes PROJECT SUMMARY/ABSTRACT Centrosomes are comprised of a pair of cylindrical centrioles and associated pericentriolar material (PCM). Their major function is to organize a bipolar mitotic spindle to mediate accurate chromosome partitioning. Centrosome dysfunction and abnormal centrosome numbers are associated with diseases such as primary microcephaly and cancer. Hence, it is important to understand the cellular mechanisms that regulate centrosome biology. Previous studies have revealed that a centrosome-associated membrane structure called the centriculum plays a critical role in regulating centrosome function. However, the mechanism by which membranes and membrane-associated proteins regulate centrosomes is unknown. Prior studies have suggested roles for the membrane-associated endocytic proteins clathrin and dynamin in regulating centrosome number and PCM assembly, respectively. However, our understanding of the mechanism by this occurs is unclear. This proposal uses C. elegans as a model system to elucidate how the vesicular trafficking proteins clathrin (clathrin heavy chain is CHC-1 in C. elegans) and dynamin (DYN-1 in C. elegans) regulate centrosomes. Our long-term goal is to understand how membranes and membrane-associated proteins regulate centrosome biology. The overall objectives in this application are to understand how the membrane-associated endocytic proteins CHC-1 and DYN-1 collaborate with the core centrosome proteins ZYG-1 and SPD-2, respectively to regulate centrosome number and PCM assembly. Our central hypothesis is that CHC-1 and DYN-1 regulate ZYG-1 and SPD-2 protein localizations respectively, either in an endocytosis-dependent or in an endocytosis-independent manner to ensure a properly built and functioning centrosome. Our hypothesis will be tested by pursuing two specific aims: 1) Determine the mechanism by which CHC-1 and ZYG-1 interact and elucidate the effect of perturbing this interaction on centrosome duplication and ZYG-1 localization. 2) Test the hypothesis that DYN-1 plays a critical role in PCM assembly by controlling the amount of SDP-2 recruitment via vesicular trafficking. We will utilize cell and molecular biology techniques and C. elegans genetics to test our specific aims. The research proposed in this application is innovative because we are the first to investigate the contribution of the membrane-associated vesicular trafficking proteins CHC-1 and DYN-1 to centrosome biology in an in vivo model system. Developing therapeutic interventions for any disease begins with understanding the fundamental mechanisms underlying disease-associated processes at the level of basic science. The proposed research is significant because the dysregulation of centrosome number and function is associated with a host of diseases, making a more comprehensive understanding of how centrosome processes are regulated at the mechanistic level imperative.


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 = -$4,700 )
2025	2024	UNIVERSITY OF TULSA	800 S TUCKER DR	TULSA	OK	74104	TULSA	USA	Biomedical Research and Research Training	002	1	8/1/2025	NEW	$2
2025	2024	NORTH CAROLINA AGRICULTURAL AND TECHNICAL STATE UNIVERSITY	1601 E MARKET ST	GREENSBORO	NC	27411	GUILFORD	USA	Biomedical Research and Research Training	001	2	7/23/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$417,507
2025	2024	UNIVERSITY OF TULSA	800 S TUCKER DR	TULSA	OK	74104	TULSA	USA	Biomedical Research and Research Training	000	1	7/22/2025	NEW	-$422,209
														Subtotal = -$4,700

Issue Date FY: 2024 ( Subtotal = $426,000 )
2024	2024	UNIVERSITY OF TULSA	800 S TUCKER DR	TULSA	OK	74104	TULSA	USA	Biomedical Research and Research Training	000	1	6/27/2024	NEW	$426,000
														Subtotal = $426,000

Grand Total All Awards = $421,300

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Role of Vesicular Trafficking Proteins in Regulating Centrosomes

Award Number: R15GM152965

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: 07/01/2024

PERIOD OF PERFORMANCE END DATE: 08/08/2024

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