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Supplement For Continuity Through Major Life Event

Award Number: K99GM154059
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 09/10/2024
PERIOD OF PERFORMANCE END DATE: 07/31/2026

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Supplement For Continuity Through Major Life Event - PROJECT SUMMARY Cells are the building blocks that comprise and pattern multicellular organisms from plants to humans, and many types of cells themselves exhibit complex shapes and patterns. While we understand many of the molecular components of cells, we know much less about how they are assembled to create patterns at the cellular scale. RNA regionalization, or spatially distinct localization of transcripts, is known to contribute to cellular morphology and function in various cells such as neurons. Several diseases that arise in the brain, from depression to Alzheimer’s, may also partly be explained by mislocalized RNA. To understand how cells are patterned via RNA regionalization, we must also understand how the genome is spatially organized as nuclear architecture and chromatin structure both influence gene expression. My proposal leverages the strengths of a unicellular system, Stentor coeruleus, that possesses a complex cellular architecture including a mouth and tail, and is capable of regeneration when damaged. Stentor cells also harbor a transcriptionally active macronucleus that spans the 1 mm long axis of the cell with a unique beads-on-a-string configuration and contains more than 50,000 copies of the genome. These properties enable microsurgery to physically separate regions of the cell and its nucleus along a defined axis for sub-cellular and sub-nuclear analyses of RNA and genome regionalization by sequencing, which is not possible in traditional model systems. First, I will examine two independent models for cellular patterning by RNA regionalization. With RNAi and RNA- sequencing in bisected cells, I will determine whether RNA transport promotes cellular asymmetry by defining the cytoskeletal elements and associated motors required for RNA regionalization. With RNA-sequencing in individual ‘nodes’ of the macronucleus, I will also determine if gene expression is regionalized, thereby reducing the distance RNA must travel before it reaches its destination. Then, with chromatin profiling and whole-genome sequencing, I will determine whether the genome is regionalized by spatial chromatin regulation or differential localization of genes themselves and establish whether these are associated with RNA regionalization and ultimately cellular patterning. To conduct this work, I will receive training in cell biology and imaging, chromatin biology and genomics, as well as in tool development in emerging model organisms. This innovative work will serve as the foundation for my independent research program, which aims to advance our understanding of the consequences of disrupted cellular patterning in development and disease.


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 = $41,862 )
2026	2026	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Biomedical Research and Research Training	000	2	1/20/2026	SUPPLEMENT FOR EXPANSION	$41,862
														Subtotal = $41,862

Issue Date FY: 2025 ( Subtotal = $124,767 )
2025	2025	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Biomedical Research and Research Training	000	2	7/10/2025	NON-COMPETING CONTINUATION	$124,767
														Subtotal = $124,767

Issue Date FY: 2024 ( Subtotal = $124,767 )
2024	2024	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Biomedical Research and Research Training	000	1	9/10/2024	NEW	$124,767
														Subtotal = $124,767

Grand Total All Awards = $291,396

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Supplement For Continuity Through Major Life Event

Award Number: K99GM154059

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 09/10/2024

PERIOD OF PERFORMANCE END DATE: 07/31/2026

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