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Identification and Analysis of Circadian Clock-Controlled Genes

Award Number: R35GM118022
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: 04/01/2016
PERIOD OF PERFORMANCE END DATE: 03/31/2022

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Identification and Analysis of Circadian Clock-Controlled Genes - Project Summary This is a proposal for a one year terminal Supplement to my existing MIRA grant for the purposes of finishing off, where possible, remaining activities and transitioning personnel in anticipation of my exiting full time research. Despite my plans, this transitioning has been made very difficult due to the pandemic. For context, my long term goal has been to describe in the language of genetics and biochemistry the feedback cycles and pathways that comprise intracellular circadian systems –how they work, how they are synchronized with the environment, and how time information generated by them is used to regulate the behavior of cells. This proposal for a one year Supplement focuses on the model system Neurospora, as well as on the mouse and mammalian cell lines, to understand the paradigms underlying circadian control of cell physiology and metabolism. The goal is to transition ongoing work to a state where it can be published or handed off in an orderly manner for completion. One Focus anticipates completion of a global analysis and description of the light-response network in Neurospora, using RNA sequencing, chromatin immunoprecipitation, and bioinformatics to describe the regulatory hierarchy governing the transcriptional response of the cell to light. This response is initiated by the same transcription factor that initiates control circadian response, and description of the light pathway. I believe this is achievable in the final year, is an important first step to describing the circadian transcriptional control network. This work is a restricted subset of the research approach originally anticipated. In the second Focus, we will apply our knowledge of circadian output pathways to mammalian cells, using RNA sequencing to determine the circadian profile of clock-controlled genes in adipocytes and from wt and RIP140 knockout mice. We will use RNA-seq to characterize the transcriptomes of WT and mutant cells and use chromatin immunoprecipitationto begin to dissect the role of this co-activator/co-repressor in the circadian biology of these important cell types. These experiments will probe the significance of circadian regulation to fat metabolism in a mammal, with the hope of gaining insights into the incidence in humans of diabetes, metabolic syndrome, time-of-day differences in immune function. This will complete an important step in this analysis and is achievable in a final year. These projects are complementary and mutually enriching in that they each rely on genetic and molecular techniques to dissect, and ultimately to understand, the response of cells to their environment and the organization of eukaryotic cells as a function of time.


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: 2023 ( Subtotal = -$40,604 )
2023	2021	TRUSTEES OF DARTMOUTH COLLEGE	7 LEBANON ST	HANOVER	NH	03755	GRAFTON	USA	Biomedical Research and Research Training	000	5	10/27/2022	SUPPLEMENT FOR EXPANSION	-$80
2023	2021	TRUSTEES OF DARTMOUTH COLLEGE	7 LEBANON ST	HANOVER	NH	03755	GRAFTON	USA	Biomedical Research and Research Training	001	5	5/15/2023	SUPPLEMENT FOR EXPANSION	-$40,524
														Subtotal = -$40,604

Issue Date FY: 2021 ( Subtotal = $521,495 )
2021	2021	TRUSTEES OF DARTMOUTH COLLEGE	1 HINMAN DARTMOUTH COLLEGE	HANOVER	NH	03755	GRAFTON	USA	Biomedical Research and Research Training	000	5	4/8/2021	SUPPLEMENT FOR EXPANSION	$521,495
														Subtotal = $521,495

Issue Date FY: 2020 ( Subtotal = $630,050 )
2020	2020	TRUSTEES OF DARTMOUTH COLLEGE	1 HINMAN DARTMOUTH COLLEGE	HANOVER	NH	03755	GRAFTON	USA	Biomedical Research and Research Training	000	5	3/27/2020	NON-COMPETING CONTINUATION	$630,050
														Subtotal = $630,050

Issue Date FY: 2019 ( Subtotal = $630,050 )
2019	2019	TRUSTEES OF DARTMOUTH COLLEGE	1 HINMAN DARTMOUTH COLLEGE	HANOVER	NH	03755	GRAFTON	USA	Biomedical Research and Research Training	000	4	3/28/2019	NON-COMPETING CONTINUATION	$630,050
														Subtotal = $630,050

Issue Date FY: 2018 ( Subtotal = $690,668 )
2018	2018	TRUSTEES OF DARTMOUTH COLLEGE	1 HINMAN DARTMOUTH COLLEGE	HANOVER	NH	03755	GRAFTON	USA	Biomedical Research and Research Training	001	3	5/24/2018	NON-COMPETING CONTINUATION	$63,005
2018	2018	TRUSTEES OF DARTMOUTH COLLEGE	1 HINMAN DARTMOUTH COLLEGE	HANOVER	NH	03755	GRAFTON	USA	Biomedical Research and Research Training	000	3	3/28/2018	NON-COMPETING CONTINUATION	$567,045
2018	2018	TRUSTEES OF DARTMOUTH COLLEGE	1 HINMAN DARTMOUTH COLLEGE	HANOVER	NH	03755	GRAFTON	USA	Biomedical Research and Research Training	002	3	9/7/2018	SUPPLEMENT FOR EXPANSION	$60,618
														Subtotal = $690,668

Issue Date FY: 2017 ( Subtotal = $630,050 )
2017	2017	TRUSTEES OF DARTMOUTH COLLEGE	1 HINMAN DARTMOUTH COLLEGE	HANOVER	NH	03755	GRAFTON	USA	Biomedical Research and Research Training	001	2	7/18/2017	NON-COMPETING CONTINUATION	$63,005
2017	2017	TRUSTEES OF DARTMOUTH COLLEGE	1 HINMAN DARTMOUTH COLLEGE	HANOVER	NH	03755	GRAFTON	USA	Biomedical Research and Research Training	000	2	4/3/2017	NON-COMPETING CONTINUATION	$567,045
														Subtotal = $630,050

Issue Date FY: 2016 ( Subtotal = $630,050 )
2016	2016	DARTMOUTH COLLEGE	11 ROPE FERRY ROAD, #6210	HANOVER	NH	03755	GRAFTON	USA	Biomedical Research and Research Training	000	1	3/31/2016	NEW	$630,050
														Subtotal = $630,050

Grand Total All Awards = $3,691,759

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Identification and Analysis of Circadian Clock-Controlled Genes

Award Number: R35GM118022

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: 04/01/2016

PERIOD OF PERFORMANCE END DATE: 03/31/2022

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