# Studies on Microtubule Binding Proteins

> **NIH NIH R37** · SCRIPPS RESEARCH INSTITUTE, THE · 2020 · $722,911

## Abstract

During cell division, chromosome pairs are collected on a spindle shaped microtubule scaffold. The pairs
 are then separated to the two poles of the spindle. Subsequently the poles move further apart, taking the
 chromosomes with them, and the cell membrane constricts into the spindle midplane, pinching the cell into
two daughters each with an exact copy of the genetic material and half of the cytoplasm of the original. This
description is a greatly simplified version of a very complicated and tightly regulated process. The
microtubules are the central players; they define the basic spindle architecture, they are the tracks that
guide chromosomes to their destinations at the various stages and they are the substrates that molecular
motors use to push the spindle poles apart before the cytoplasm is divided. The process is of fundamental
importance for both healthy and diseased cells. As cancer cells are dividing uncontrollably, the spindle is a
common target for anti-cancer drugs. The proposed work is a series of structure determinations aimed at
visualizing how critically important proteins and macromolecular complexes interact at foci of activity on the
microtubules. The regions of interest are the plus ends of kinetochore and interpolar microtubules. At the
kinetochore, coordinated microtubule assembly and disassembly result in chromosome congregation
followed by separation of the chromosome pairs. Of particular interest are protein complexes responsible for
chromosome attachment to disassembling microtubule plus ends. At the overlap region of interpolar
microtubules, crosslinking proteins and motors determine and regulate spindle length. These crucial protein
complexes will be studied. We will continue work on a protein complex that nucleates microtubule branches.
Finally, we will extend recently completed work on tubulin ligases - enzymes that make posttranslational
modifications to microtubules. The structure determinations will be carried out by cryo-electron microscopy
and image analysis. The structural results we obtain will provide the basis for a mechanistic understanding
of some of the most important events taking place on spindle microtubules during cell division.

## Key facts

- **NIH application ID:** 10004514
- **Project number:** 5R37GM052468-26
- **Recipient organization:** SCRIPPS RESEARCH INSTITUTE, THE
- **Principal Investigator:** RONALD A MILLIGAN
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $722,911
- **Award type:** 5
- **Project period:** 1995-05-01 → 2021-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10004514

## Citation

> US National Institutes of Health, RePORTER application 10004514, Studies on Microtubule Binding Proteins (5R37GM052468-26). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10004514. Licensed CC0.

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