# Cellular surfaces as regulators of biomolecular condensate assembly

> **NIH NIH K99** · DUKE UNIVERSITY · 2024 · $104,070

## Abstract

PROJECT SUMMARY. Introduction: Biomolecular condensates, composed of a concentrated network of
proteins and nucleic acids, compartmentalize cellular biochemistry. The establishment of a precise molecular
composition is critical for the biological functions of condensates. In particular, cells must assemble either (a)
coexisting condensates of distinct composition within a shared environment or (b) coexisting sub-layers of
distinct composition within the same condensate. In both cases, the mechanisms by which cells specify
compositional identity are poorly understood. In this proposal, I will examine how two types of biological
“surfaces,” (a) two-dimensional lipid membranes and (b) one-dimensional long noncoding RNA polymers,
establish condensate identity and dictate the formation of distinct layers. I hypothesize that each type of surface
regulates condensate composition and function by modifying RNA structure in distinct ways. Research: In Aim
1, I will examine how membrane surfaces modify RNA structure to control condensate identity and regulate
mRNA translation in the cytoplasm. In Aim 2, I will examine how the structural features of a long noncoding RNA
control the formation of condensates with discrete layers and regulate mRNA retention in the nucleus. The overall
outcome will be an enhanced, mechanistic understanding of how cells assemble key compartments of mRNA
function. Training: I will complete my training with Prof. Amy Gladfelter at UNC Chapel Hill. During the training
period, I will work with innovative collaborators to acquire new skills that will enable me to probe and manipulate
RNA structure and dissect the molecular driving forces of biomolecular condensation. These skillsets will
accelerate discovery during the remainder of my training and form the foundation for my independent lab.
Specifically, I will learn powerful strategies to (1) map RNA structure with Kevin Weeks at UNC; (2) study long
noncoding RNAs with Mauro Calabrese at UNC; (3) examine the spatial regulation of mRNA translation with
Chris Nicchitta at Duke University; and (4) develop mathematical models of biological self-assembly with Krishna
Shrinivas at Harvard University. Environment: Prof. Gladfelter is a supportive and inspiring mentor who fosters
creativity and collaboration. UNC Chapel Hill is a hub for world-class RNA biology and will provide valuable
opportunities to learn from experienced scientists. This K99/R00 award will enable me to pursue exciting new
research directions beyond my core skillsets, form strong collaborations with leading labs, and immerse myself
in new disciplines through a variety of courses, seminars, workshops, and conferences. Impact on Public
Health: The process of biomolecular condensation has generated intense interest in recent years, in part due to
its role in the formation of pathological aggregates that cause neurodegenerative diseases such as amyotrophic
lateral sclerosis. My work will uncover fundamental mechanisms by whi...

## Key facts

- **NIH application ID:** 10932850
- **Project number:** 5K99GM149757-02
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Wilton Thomas Snead
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $104,070
- **Award type:** 5
- **Project period:** 2023-09-21 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10932850

## Citation

> US National Institutes of Health, RePORTER application 10932850, Cellular surfaces as regulators of biomolecular condensate assembly (5K99GM149757-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10932850. Licensed CC0.

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