# Identification and Analysis of Circadian Clock-Controlled Genes

> **NIH NIH R35** · DARTMOUTH COLLEGE · 2021 · $521,495

## Abstract

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.

## Key facts

- **NIH application ID:** 10365194
- **Project number:** 3R35GM118022-05S1
- **Recipient organization:** DARTMOUTH COLLEGE
- **Principal Investigator:** JENNIFER J. LOROS
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $521,495
- **Award type:** 3
- **Project period:** 2016-04-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10365194

## Citation

> US National Institutes of Health, RePORTER application 10365194, Identification and Analysis of Circadian Clock-Controlled Genes (3R35GM118022-05S1). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10365194. Licensed CC0.

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