# Role of DNA Methylation in Dietary Restriction mediated insulin sensitivity

> **NIH NIH K01** · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · 2020 · $130,545

## Abstract

Summary/Abstract
 The research and career development activities outlined in this application have been designed to equip the
candidate, Dr. Archana Unnikrishnan, with the scientific and technical expertise necessary to become an
independent investigator in the field of aging. The proposed research aims to study the role of DNA
methylation in dietary restriction (DR) mediated insulin sensitivity. The goals of this training program are: 1.
gain hands on experience in the cutting-edge technology available to study DNA methylation; Oxidative
Bisulfite Oligonucleotide Sequencing; 2. determine the role of DNA methylation in the effect of DR on
glucoregulation; 3. determine the effect of DR on the enzymes involved in DNA methylation; and 4. gain
experience in writing grants and have a R01 funded grant by the end of the K01 award. The candidate will
receive training in novel bisulfite based next generation sequencing technology and biology of aging through
intensive coursework and hands on laboratory experience under the supervision of Drs. Arlan Richardson and
Willard Freeman. The candidate will also gain training in proteomic analysis by using mass spectrometry by
collaborating with Dr. Mike Kinter. The other major goal of this application is to enable the candidate, as a
junior faculty, to secure protected time for research activities, establish new collaborations, and develop, and
develop a novel line of research that produces competitive grant proposals for future funding.
 The research objective is to characterize and discover novel changes in DNA methylation that occur with DR
that have an effect on the transcriptome. DR is believed to retard aging and has become the ‘gold standard’ by
which other manipulations that increase lifespan are compared. Many mechanisms have been proposed for
the life-extending action of DR; however, it is still unclear as to the molecular basis of DR’s action. An
important facet of DR that has been largely overlooked by the research community is that DR can have early
effects that create a metabolic memory, which persists even when the restriction is discontinued.
 The purpose of this grant is to gather the first data on the effect of DR on DNA methylation and metabolic
memory that will allow us to test the following hypothesis: DR induces metabolic memory by inducing
changes in DNA methylation (5mC) at specific genomic regions that regulate the expression of genes
that are involved in insulin sensitivity. This hypothesis will be tested in the following aims: 1) assess the
effect of DR on DNA methylation and hydroxymethylation across gene regulatory regions of tissues involved
in glucoregulation; 2) determine the transcriptional phenotype related to the changes in DNA methylation in
tissues involved in glucoregulation; 3) Determine the effect of DR on the pathway involved in DNA
methylation and demethylation.

## Key facts

- **NIH application ID:** 9965714
- **Project number:** 5K01AG056655-03
- **Recipient organization:** UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
- **Principal Investigator:** Archana Unnikrishnan
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $130,545
- **Award type:** 5
- **Project period:** 2018-09-30 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9965714

## Citation

> US National Institutes of Health, RePORTER application 9965714, Role of DNA Methylation in Dietary Restriction mediated insulin sensitivity (5K01AG056655-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9965714. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*