# Single-molecule interrogation of microtubule dynamics mechanisms

> **NIH NIH R01** · UT SOUTHWESTERN MEDICAL CENTER · 2020 · $394,992

## Abstract

The microtubule (MT) cytoskeleton is essential to eukaryotic cells: microtubules are dynamic polymers required
for chromosome segregation and intracellular organization, and are the direct targets of anti-cancer
chemotherapeutics like taxol and the Vinca alkaloids. The dynamic properties of MTs are central to their
function, and they derive from the biochemical properties of individual αβ-tubulin subunits and how they
interact within the MT lattice. The quantitative mechanisms of MT dynamics have been difficult to understand
because the MT end is a complex biochemical environment where individual tubulins adopt different
conformations and can have different numbers of neighbor contacts, and because it has not been possible to
measure individual interactions directly. With the goal of quantitatively examining the contributions of
longitudinal and lateral interactions, nucleotide state, MT end configurations, and lattice-induced
conformational changes to MT assembly and switching, we recently showed that interactions between yeast
αβ-tubulin and the MT end can be observed at the single-molecule level and quantified with high temporal
resolution using interferometric scattering (iSCAT) microscopy. Comparative studies of yeast and human
tubulin are proposed to establish general mechanisms of microtubule dynamics. Aim 1 will use iSCAT to
measure and quantify the interactions of human and yeast αβ-tubulin with the end of a stable microtubule
seed, and how these interactions depend on nucleotide state. Aim 2 will use iSCAT and other techniques to
measure how a mutation that perturbs the αβ-tubulin propensity for conformational change affects biochemical
interactions with the microtubule end and microtubule growth and shrinking kinetics more generally. Aim 3 will
use iSCAT and other techniques to measure how different doses of an αβ-tubulin mutant with its plus-end
“blocked” affect microtubule elongation and catastrophe. The results will be used to construct a biochemical
model for microtubule dynamics that will deepen the understanding of catastrophe.

## Key facts

- **NIH application ID:** 9865751
- **Project number:** 1R01GM135565-01
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Luke W Rice
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $394,992
- **Award type:** 1
- **Project period:** 2020-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9865751

## Citation

> US National Institutes of Health, RePORTER application 9865751, Single-molecule interrogation of microtubule dynamics mechanisms (1R01GM135565-01). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9865751. Licensed CC0.

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