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How are human chromosomes captured and pulled apart into two equal sets?

Supervisor: Dr Viji M Draviam-Sastry

Deadline: 31 August 2015

Funding: self-funded only

Background

An average human being experiences trillions of cell division events. During each round of cell division, cells must ensure the accurate segregation of chromosomes. For this purpose, rope-like microtubules must properly capture chromosomes at specialised multi-protein platform called the kinetochore. The kinetochores acts as a macromolecular machine; mutations in kinetochore proteins can lead to failure in capturing and segregating the genome into two accurate sets, leading to aneuploidy. Aneuploidy is a hallmark of aggressive cancers. To understand why aneuploidy is caused in cancers, it is important to first identify the molecular lesions that can cause aneuploidy. So, our research goal is to identify the important molecular parts of the kinetochore, understand how it works and determine the consequence of its failure.

Recent work in the Draviam group showed that kinetochores are first captured along microtubule walls and then brought to microtubule-ends. This remarkable change in the plane of kinetochore-microtubule interaction is important because only when the kinetochore is tethered to microtubule-ends, the growth and shrinkage of microtubule-ends can be translated into pushing and pulling forces to move chromosomes.

The student will be trained to combine high-resolution live-cell microscopy, biochemistry and molecular biology techniques for determining how microtubules capture kinetochores and impart forces to pull apart chromosomes into two equal sets. For this purpose, the student will first make mutants of outer-kinetochore proteins that interact with microtubules and then explore its impact on chromosome-microtubule attachment and ultimately chromosome segregation. The multi-disciplinary project is ideal for students interested in working at the interface of cancer and basic biology research.

Funding

Research expenses will be covered. Applications are invited from candidates with at least an upper-second class honours degree in an area relevant to the project (e.g. Biochemistry, Molecular/Cellular Biology, Biomedical Sciences). Written and spoken English skills are essential. For more information, email Dr Viji

Application process

  • Informal enquires are encouraged. Please contact Dr Viji with cover letter, CV, and the names and contact details of two academic referees.
  • We encourage you to contact Dr Viji in the first instance, then submit an online application.

References

  • Ochi T et al PAXX, a paralog of XRCC4 and XLF, interacts with Ku to promote DNA double-strand break repair Science 2015 347 (6218): 185-188.
  • Tamura et al., Mitosis phase-specific interactions of EB1 reveal two pools of SKAP associated with distinct mitotic outcomes. (Biology Open 2015 (4): 155-169).
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