# Understanding the role of the conserved KIN-20 protein in regulating gene expression and development in C. elegans

> **NIH NIH R15** · COLGATE UNIVERSITY · 2021 · $404,572

## Abstract

PROJECT SUMMARY
Proper timing of gene expression is essential for cellular and organismal development. The C.
elegans heterochronic pathway, which regulates developmental timing, is thought to be an
ancestral form of the circadian clock in other organisms. Within this pathway, multiple genes
interact to mediate proper development. Misregulation of these genes causes inappropriate cell
growth and ultimately death in C. elegans, and cancer and other developmental disorders in
humans. An essential member of the circadian clock is the Period protein whose homolog, LIN-
42, is an important regulator of developmental timing in C. elegans. LIN-42 functions as a
transcriptional repressor of multiple genes including the conserved lin-4 and let-7 microRNAs,
which are also essential members of the heterochronic pathway. Like other Period proteins, levels
of LIN-42 oscillate throughout development. In other organisms this cycling is controlled in part
by phosphorylation and subsequent degradation. KIN-20 is the C. elegans homolog of the
Drosophila Period protein kinase Doubletime. Worms containing a large deletion in kin-20 have a
significantly smaller brood size, develop slower than wild type C. elegans, and display
uncoordinated locomotion. We have previously shown that KIN-20 impacts lin-42 mutant
phenotypes and LIN-42 protein levels, and that KIN-20 is important for post-transcriptional
regulation of mature let-7 and lin-4 microRNA expression. However, the mechanisms by which
KIN-20 regulates LIN-42, microRNA biogenesis, and development in C. elegans remain
poorly understood. Accordingly, this proposal seeks to understand these mechanisms through
three integrated specific aims. In Aim 1, we will characterize the relationship between KIN-20 and
LIN-42 to better understand how KIN-20 regulates LIN-42. In Aim 2, we will determine the role of
KIN-20 in microRNA production. In Aim 3, we will investigate the role of KIN-20 in development.
Altogether our findings will enhance our understanding of the molecular mechanisms underlying
developmental timing and thus elucidate new targets for diseases associated with cellular
developmental defects including cancer. Importantly, the experiments described here will be
performed by undergraduate students, which will significantly enhance the ability of Colgate
University to provide undergraduate students with significant opportunities for independent
research in preparation for careers in developmental biology and the biomedical sciences.

## Key facts

- **NIH application ID:** 10114434
- **Project number:** 1R15HD104101-01
- **Recipient organization:** COLGATE UNIVERSITY
- **Principal Investigator:** Priscilla Van Wynsberghe
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $404,572
- **Award type:** 1
- **Project period:** 2021-04-12 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10114434

## Citation

> US National Institutes of Health, RePORTER application 10114434, Understanding the role of the conserved KIN-20 protein in regulating gene expression and development in C. elegans (1R15HD104101-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10114434. Licensed CC0.

---

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