# Structure-function properties in liquid organelles

> **NIH NIH R01** · KANSAS STATE UNIVERSITY · 2024 · $313,123

## Abstract

Project Abstract
 Biomolecular condensates are emerging as central to cellular functions in a wide variety of con-
texts. These condensates often have liquid properties and are assembled from multivalent, polymer-like
molecules. Together, these observations suggest a disordered network of interactions stabilizing the
condensate. Liquid systems are inherently disordered, which would seem to preclude the level of order
necessary for structure-function properties to emerge. However, preliminary results have shown that,
hidden within the liquid disorder, is a hierarchy of molecular assemblies that give structure to the uid.
Furthermore, this structure within the contacts stabilizing the liquid confers crucial functional features
to the condensates. This means that in order to understand how these condensates function, it is
necessary to identify structure in disordered systems. This poses a challenge to the eld of structural
biology because this hierarchical structure cannot be resolved by workhorse techniques like X-ray, NMR,
and cryo-EM. The proposed research will establish methods to identify and characterize structure within
liquid condensates. These methods are based on theoretical modeling using an iterative re nement
procedure analogous to structure determination by NMR. This will be done in two systems that are each
featured in a speci c aim. The rst system is a model system for phase separation that removes com-
plications with identifying and quantifying interaction sites. In determining the microscopic structure
of this \sticker and spacer" binding system, which is thought to be a common motif in liquid conden-
sates, this aim will establish basic principles of how molecular structure can dictate spatial organization
on lengthscales ranging from the recruitment molecular clients to organelle segregation/colocalization.
The second aim will develop the structural modeling techniques on the nucleolus. This nuclear organelle
serves as the assembly site for ribosomes. The proposed research will use in vitro phase separation data
to understand the primary molecular interactions within the granular component (GC) where rRNAs
and protein assemble into ribosomal subunits. The interactions in the GC are primarily electrostatic,
which is di erent than the sticker and spacer motif that is the focus of Aim 1. Next, these interactions
will be used to build a kinetic theory of ribosome subunit assembly. This model will establish how the
molecular structure of GC components facilitates ribosome assembly. The theories for generated in both
aims will be analytic, meaning that they will allow for a thorough exploration of parameter space and
can be readily applied to other systems.

## Key facts

- **NIH application ID:** 10829434
- **Project number:** 5R01GM141235-04
- **Recipient organization:** KANSAS STATE UNIVERSITY
- **Principal Investigator:** Jeremy David Schmit
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $313,123
- **Award type:** 5
- **Project period:** 2021-05-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10829434

## Citation

> US National Institutes of Health, RePORTER application 10829434, Structure-function properties in liquid organelles (5R01GM141235-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10829434. Licensed CC0.

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