# Development Control in C. elegans

> **NIH NIH R01** · UNIVERSITY OF COLORADO · 2020 · $297,357

## Abstract

Project Summary
How animals regulate growth, development and behaviors in response to changes in nutrient
availability and metabolic status is a fundamental biological problem that is closely related to
human diseases and health. While major advances have been made over the last decade in
understanding TOR, insulin receptor and other signaling systems that sense the levels of sugar
and amino acids to control various cellular and physiological functions, the study of the
mechanisms by which cells and animals respond to changes in nucleotide levels to regulate
development and other physiological functions is lacking, even though nucleotide levels have been
shown to impact several cellular processes including cancer progression and certain human
disorders. The goal of this proposal is to discover and analyze the mechanism of such a
nucleotide-responsive regulatory system.
By using genes involved in nucleotide metabolism in both sthe worm and its food source E. coli, we
have established a unique model system where we observe a profound impact of uridine and
thymidine (referred to as U/T) on germline development. Results from our preliminary study,
including a suppressor screen, have indicated two key factors in the U/T sensing system leading to
the hypothesis that an unknown system involving a ribonuclease acts upstream of a Notch
signaling pathway to regulate germline proliferation and pyrimidine metabolic pathways. We will
test this hypothesis by studies under three specific aims: (1) determine how Notch receptor (glp-1)
expression is regulated by U/T levels, including the identification of the U/T-responsive element
and potential upstream regulator; (2) determine if a novel ribonuclease (scdd-1), identified from our
genetic screen, mediates the impact of U/T level on glp-1 expression; (3) investigate the potential
regulation of pyrimidine metabolic pathways by U/T levels scdd-1; and (4) investigate the
mechanism of scdd-1 function.
By connecting nucleotide availability to developmental programs and metabolism, the results from
these studies will likely present an important conceptual advance in the fields of nucleotide
metabolism, development and nutritional science. Such findings may also provoke others to
evaluate the impact of nucleotide quality in food or nutritional supplements on human health,
especially for those with genetic risks for certain metabolic diseases.

## Key facts

- **NIH application ID:** 9861243
- **Project number:** 5R01GM047869-25
- **Recipient organization:** UNIVERSITY OF COLORADO
- **Principal Investigator:** MIN HAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $297,357
- **Award type:** 5
- **Project period:** 1992-08-01 → 2021-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9861243

## Citation

> US National Institutes of Health, RePORTER application 9861243, Development Control in C. elegans (5R01GM047869-25). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9861243. Licensed CC0.

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