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Studying the mammalian regulatory circuits by developing single-cell multi-omics technologies

Award Number: K99HG011483
ORGANIZATION: NATIONAL HUMAN GENOME RESEARCH INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 12/07/2020
PERIOD OF PERFORMANCE END DATE: 04/24/2022

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Studying the mammalian regulatory circuits by developing single-cell multi-omics technologies - Project Summary/Abstract How the identical genome sequence produces diverse cell types during development remains a fundamental question in biology. Recent technology advancements in single-cell genomics provided excellent opportunities to study the molecular profiles during development and in disease at unprecedented resolution. However, monitoring individual modalities from single cells at a time runs the risk of obtaining only partial pictures from the complex regulatory network. Multi-modal single-cell genomics tools would be desired to overcome this limitation. I recently invented a method for ultra-high-throughput joint analysis of open chromatin and transcriptome from the same single cells (Paired-seq) and demonstrated its potential for comprehensive investigations of the cell- type-specific regulatory programs from heterogenous brain tissues. In this K99/R00 application, I propose to further develop a set of new single-cell multi-omics tools to study the dynamic and cell-type-specific regulatory circuits during mammalian development. I will improve the sensitivities and coverages of Paired-seq and develop a computational method for single-cell multi-omics analysis from the phenotypic level (Aim1). Subsequently, I will further develop a method for high-throughput single-cell joint analysis of histone modifications/transcription factors binding with gene expression (Paired-tag) for analysis of molecular programs from the mechanistic level (Aim2). Finally, I will apply these technologies to study the dynamic and cell-type-specific molecular programs in mammalian developing germ cells, and to identify and validate novel regulators during this process (Aim3). Overall, the results from this proposal will provide new technologies for the study of epigenetic programs in complex tissues and during development at single-cell resolution, and providing more complete views of the gene regulatory circuits during mammalian germ cell development. My career goal is to lead an independent research group focusing on integrating novel experimental and computational technologies to understand the underlying principles controlling mammalian development. During the K99 phase, I will continue to receive experimental and computational training from my postdoctoral mentor Dr. Ren and collaborators/advisory committee at UC San Diego and the Salk Institute. The rigorous mentored support and results obtained in the K99 phase will facilitate my transition to an independent investigator in the R00 phase and lay the foundation for my future career.


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: 2022 ( Subtotal = $60,200 )
2022	2022	LUDWIG INSTITUTE FOR CANCER RESEARCH LTD	8950 VILLA LA JOLLA DR STE C135	LA JOLLA	CA	92037	SAN DIEGO	USA	Human Genome Research	000	2	11/5/2021	NON-COMPETING CONTINUATION	$113,415
2022	2022	LUDWIG INSTITUTE FOR CANCER RESEARCH LTD	8950 VILLA LA JOLLA DR	LA JOLLA	CA	92037	SAN DIEGO	USA	Human Genome Research	002	2	9/15/2022	NON-COMPETING CONTINUATION	-$5,990
2022	2022	LUDWIG INSTITUTE FOR CANCER RESEARCH LTD	8950 VILLA LA JOLLA DR STE C135	LA JOLLA	CA	92037	SAN DIEGO	USA	Human Genome Research	001	2	6/17/2022	NON-COMPETING CONTINUATION	-$47,225
														Subtotal = $60,200

Issue Date FY: 2021 ( Subtotal = $113,415 )
2021	2021	LUDWIG INSTITUTE FOR CANCER RESEARCH LTD	8950 VILLA LA JOLLA DR STE C135	LA JOLLA	CA	92037	SAN DIEGO	USA	Human Genome Research	000	1	12/7/2020	NEW	$113,415
														Subtotal = $113,415

Grand Total All Awards = $173,615

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Studying the mammalian regulatory circuits by developing single-cell multi-omics technologies

Award Number: K99HG011483

ORGANIZATION: NATIONAL HUMAN GENOME RESEARCH INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 12/07/2020

PERIOD OF PERFORMANCE END DATE: 04/24/2022

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