# Structural Biology Studies of Ribosome Biogenesis Network

> **NIH NIH R01** · FLORIDA STATE UNIVERSITY · 2021 · $17,308

## Abstract

Description: Ribosome is the evolutionarily conserved molecular machine responsible
for synthesis of proteins. In eukaryotic cells, ribosome is produced in a biophysically
distinct subnuclear compartment, the nucleolus, through a cascade of energy-driven
events. This process underlies a number of genetic diseases and is a major target for
anti-cancer and anti-neurodegeneration therapeutics. However, the physical interactions
of the network required for this process remain largely uncharacterized. This application
will characterize a key molecular complex called R2TP that acts early in ribosome
production by facilitating assembly of several ribosome production enzymes. R2TP has
a wide client base, collaborates with a general protein folding chaperone, heat shock
protein 90 (Hsp90), and delivers clients to the nucleolus. The Li laboratory uses a
combination of structural biology, biochemical, and genetics methods to provide
functional insights on R2TP and its impact on ribosome production. Exceptionally
detailed three-dimensional views of R2TP itself and those R2TP acts upon will be
obtained and analyzed along with the available functional data. Two specific aims are
designed to 1) establish the structure and function cycle of R2TP; 2) elucidate the
physiological role of R2TP. Results of this study will identify new molecular sites for
developing anti-cancer and anti-neurodegenerative drugs through controls of ribosome
production and degradation. The Li laboratory has assembled a team of scientists with
complementary expertise in x-ray crystallography, high-throughput electron
cryomicroscopy, mass spectrometry, biophysics, protein biochemistry, and yeast
genetics in order to maximize the chance of successes while mitigating risks.
Relevance: Aberrant nucleolar morphology and function have been linked to cancers
and Alzheimer's disease in human. Correspondingly, R2TP and its client proteins have
been identified as key regulators of nucleolar morphology. Whereas more than fifteen
types of anti-cancer drugs have been investigated or in clinical trials that target
molecules involved in this pathway, none is known for anti-neurodegeneracy. Though
effective in cell-death assays, the pharmacological basis of many compounds remains to
be explained and some develop resistance in cells. The proposed research provides
platforms for explaining the actions of the existing drugs while discovering new ones.

## Key facts

- **NIH application ID:** 10389719
- **Project number:** 3R01GM124622-04S1
- **Recipient organization:** FLORIDA STATE UNIVERSITY
- **Principal Investigator:** Hong Li
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $17,308
- **Award type:** 3
- **Project period:** 2018-09-10 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10389719

## Citation

> US National Institutes of Health, RePORTER application 10389719, Structural Biology Studies of Ribosome Biogenesis Network (3R01GM124622-04S1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10389719. Licensed CC0.

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