# Molecular, material, and structural design principles of centrosomes

> **NIH NIH R35** · UT SOUTHWESTERN MEDICAL CENTER · 2021 · $409,896

## Abstract

Project Summary
Centrosomes nucleate microtubule arrays and act as force-coordinating centers to
position nuclei and segregate chromosomes, which are essential activities during early
embryogenesis and neural development. While much is understood about the regulation
of centrosome number, much less is known about molecular mechanisms determining
centrosome size, microtubule nucleation capacity, and resistance to forces. The goal of
this proposal is to reveal how molecular-level interactions between centrosome proteins
determine the activity, emergent material properties, and ultrastructure of PCM, the most
substantial layer of a centrosome.
I hypothesize that PCM is an amorphous hydrogel whose material state (e.g., strength,
elasticity) is regulated by phospho-tunable connections between coiled-coil scaffolding
proteins. I further hypothesize that fine-tuning of scaffold structure and material properties
regulates PCM size, activity, and resistance to microtubule-dependent pulling forces. I
propose to test these hypotheses using two innovative techniques that I recently
developed: a minimal PCM reconstitution system and an optical method to perform nano-
rheology of PCM in living embryos. In addition, I propose to develop in-cell cryo-electron
tomography to visualize PCM ultrastructure with sub-10 nm resolution. These
experiments are designed to 1) identify the minimal components needed to generate
consistently sized, fully active PCM, 2) discover key regulators and material design
principles that allow PCM to resist microtubule-pulling forces, and 3) generate the highest-
resolution structural atlas of native centrosomes to date. This proposal is significant
because it will illuminate how centrosome function is determined and regulated at the
molecular level, which will provide mechanistic insight into human disorders caused by
centrosome dysfunction, such as microcephaly, primordial dwarfism, and various
cancers.

## Key facts

- **NIH application ID:** 10274290
- **Project number:** 1R35GM142522-01
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Jeffrey B Woodruff
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $409,896
- **Award type:** 1
- **Project period:** 2021-08-01 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10274290

## Citation

> US National Institutes of Health, RePORTER application 10274290, Molecular, material, and structural design principles of centrosomes (1R35GM142522-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10274290. Licensed CC0.

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