# The identification of fundamental molecular regulators of ribosomal DNA and nucleolar organization in fission yeast

> **NIH NIH F30** · UNIVERSITY OF KANSAS MEDICAL CENTER · 2024 · $56,974

## Abstract

Project Abstract
Ribosome production relies on a nuclear organelle called the nucleolus. Within this structure, ribosomal DNA
(rDNA) is transcribed to form RNA transcripts that associate with ribosomal proteins. Nucleolar architecture is
altered in many human diseases including numerous cancers, prompting several studies to search for
regulators of nucleolar morphology. While these studies rely on analysis of nucleolar proteins or ribosome
production to identify molecular regulators, few studies have defined cell cycle-specific mechanisms for
regulating nucleolar structure. Furthermore, no studies have examined the impact of rDNA spatial organization
on nucleolar morphology despite rDNA loci’s known role as Nucleolar Organizer Regions. The long-term goal
is to understand conserved regulatory mechanisms of rDNA and nucleolar organization. The overall objectives
of this proposal are to (i) to identify molecular regulators of rDNA spatial organization and (ii) define the
processes driving cell cycle-regulated nucleolar morphology. The central hypothesis is that the spatial
organization of rDNA is regulated, in part, by chromosome organizing proteins and ribosome biogenesis;
furthermore, these ribosome biogenesis processes are cell cycle-regulated, driving dynamic reorganization of
nucleolar morphology during interphase. The rationale for this study is that identification of conserved
molecular regulators of rDNA and nucleolar organization in fission yeast will provide a template for future
research in higher organisms. This central hypothesis will be tested by two specific aims: 1) identify molecular
regulators of rDNA spatial organization in fission yeast; and 2) define the processes driving cell cycle-regulated
nucleolar morphology. For aim 1, a novel tool for analysis of rDNA spatial organization in live cells has been
developed in fission yeast. This tool will be used to quantify rDNA spatial organization by fluorescence
microscopy in candidate mutants with altered chromosome organization and DNA topology factors. This
analysis will be expanded by a genome-wide high-throughput imaging screen to broadly identify regulators of
rDNA spatial organization. Aim 2 will apply fluorescence microscopy, cell biology, and molecular biology
approaches to examine the role of cell cycle-regulated ribosome biogenesis factors in interphase nucleolar
morphology. These studies examine rDNA and nucleolar morphology in fission yeast, a model system notable
for its application to higher organisms and ease of genetic manipulation. To understand the relationship
between nucleolar morphology and human disease, the regulatory mechanisms behind rDNA and nucleolar
organization must be identified. This study applies innovative imaging tools with advanced cellular and
molecular biology techniques to broadly identify fundamental molecular regulators of rDNA and nucleolar
morphology, providing a framework for future studies in human cells.

## Key facts

- **NIH application ID:** 10993993
- **Project number:** 3F30GM140716-04S1
- **Recipient organization:** UNIVERSITY OF KANSAS MEDICAL CENTER
- **Principal Investigator:** Alexandria Jane Cockrell
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $56,974
- **Award type:** 3
- **Project period:** 2021-01-03 → 2025-01-02

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10993993

## Citation

> US National Institutes of Health, RePORTER application 10993993, The identification of fundamental molecular regulators of ribosomal DNA and nucleolar organization in fission yeast (3F30GM140716-04S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10993993. Licensed CC0.

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