# Cell and Chemical Biology of Microtubules

> **NIH NIH R35** · HARVARD MEDICAL SCHOOL · 2021 · $825,981

## Abstract

Project Summary/Abstract:
We will investigate the cell and chemical biology of microtubules in order to answer fundamental
questions of cell organization and improve treatment of human diseases. Microtubules are
dynamic, linear polymers of the protein tubulin. They physically organize the cytoplasm of most
human cells, and serve as transport tracks for moving cellular components. They are particularly
important during cell division, when they build mitotic spindles which separate chromosomes, and
in neurons, where they provide transport tracks for supplying distant synapses with new building
blocks. We will probe cell division mechanism using frog eggs as a model system. Our work may
help treat infertility and understand mistakes in cell division that give rise to birth defects. We k now
most of the proteins required for cell division, but we do not know how they work together to build
spindles or position cleavage furrows. We will use a new tool, quantitative mass spectrometry, to
simultaneously measure hundreds of proteins in mitotic spindles in frog egg extracts, and how they
compete for binding sites on microtubules. We will also combine microscopy, biochemistry and
mathematical modeling to learn how the spindle communicates with the cell surface to position
cleavage furrows. In neurons, we will investigate how tubulin is transported down axons, and test a
new hypothesis in which stathmin proteins serve as transport adapters. This work will address a
fundamental question in neuronal cell biology, and may help treat motor neuron disease (ALS).
Drugs that target microtubules and are used as medicines can provide important insights into
microtubule biology in adult human tissues. These include paclitaxel, which is used to treat breast
and lung cancer, and colchicine, which is used to treat gout and other inflammatory diseases. We
understand the molecular actions of these drugs on microtubules in detail, but not how they act in
the human body to treat disease. We have developed new hypothesis for the therapeutic action of
both drug classes, and will test these in cell culture and rodent models. This work could lead to
new uses of old drugs, for example we suspect low doses of colchicine might be useful to prevent
heart attacks and slow the progression of lung cancer. It could also lead to replacement drugs that
are more active and less toxic.
PHS 398/2590 (Rev. 11/07) Continuation Format Page

## Key facts

- **NIH application ID:** 10176535
- **Project number:** 5R35GM131753-03
- **Recipient organization:** HARVARD MEDICAL SCHOOL
- **Principal Investigator:** Timothy J Mitchison
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $825,981
- **Award type:** 5
- **Project period:** 2019-06-07 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10176535

## Citation

> US National Institutes of Health, RePORTER application 10176535, Cell and Chemical Biology of Microtubules (5R35GM131753-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10176535. Licensed CC0.

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