# Biology and Biochemistry of the Microtubule Cytoskeleton

> **NIH NIH R35** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2024 · $243,063

## Abstract

PROJECT SUMMARY/ABSTRACT
Biology and Biochemistry of the Microtubule Cytoskeleton
Microtubules are cytoskeletal polymers that are vital for a wide range of cellular functions. They serve as tracks
for microtubule-based motor proteins (i.e., kinesin and cytoplasmic dynein), and perform work when their ends
attach to subcellular structures such as kinetochores. Most microtubule-based processes rely on assembly of
microtubules into higher order structures such as the mitotic spindle. This in turn depends on cellular factors
such as microtubule-associated proteins (MAPs) and microtubule motors, which bind microtubules and organize
them in three-dimensional space. How MAPs and motors drive assembly of microtubule-based arrays is not fully
understood, particularly under conditions of stress. In addition, the complexity of the microtubule system is
augmented by post-translational modifications (PTMs) that are “written” onto microtubules; PTMs alter the affinity
of MAPs and motors for the microtubule lattice, providing a mechanism to create functionally distinct subsets of
microtubules. Our research is focused on understanding how MAPs and motor proteins engage the MT
cytoskeleton to orchestrate essential cellular processes. To address this and fill gaps in our knowledge we: (i)
Discovered a second pathway that drives assembly of the mitotic spindle, and developed inhibitors against a
motor protein that plays a key role in this pathway; (ii) Developed a screening pipeline to identify proteins that
bind to microtubules in a manner that depends on tubulin PTMs; and (iii) Identified a mechanism that may explain
how tubulin PTMs are written onto the microtubule lattice. The research proposal benefits from our expertise and
will combine in vitro reconstitution and cell biology approaches to address long-standing questions: (a) How do
MAPs and motor proteins work together to build the mitotic spindle?; (b) What are the functional outputs of tubulin
PTMs?; and (c) How are MTs selected for post-translational modification? Our research will provide new insights
into fundamental mechanisms that regulate the biological and biochemical properties and functions of the
microtubule cytoskeleton and uncover general principles that inform on other cellular processes (e.g.,
microtubule organization in neurons).

## Key facts

- **NIH application ID:** 10842069
- **Project number:** 1R35GM153209-01
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Ryoma Ohi
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $243,063
- **Award type:** 1
- **Project period:** 2024-04-01 → 2029-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10842069

## Citation

> US National Institutes of Health, RePORTER application 10842069, Biology and Biochemistry of the Microtubule Cytoskeleton (1R35GM153209-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10842069. Licensed CC0.

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