How do human cells ensure the accurate segregation of chromosomes?
Supervisor: Professor Viji Draviam
Aneuploidy (incorrect number of chromosomes) is a hallmark of aggressive cancers, but the underlying molecular cause is unclear. The PhD student will aim to discover molecular mechanisms that prevent aneuploidy in human cells.
When a cell divides into two, its microtubules must properly capture each chromosome at specialised multi-protein structures called kinetochores. Therefore, to understand how aneuploidy arises, we should understand how kinetochores are captured by microtubules. Recent high-resolution microscopy work in the Draviam group showed that kinetochores are first captured along microtubule walls and then brought to microtubule-ends. This is an important cellular event because when the kinetochore is not tethered to microtubule-ends, the growth and shrinkage of microtubule-ends can not push or pull chromosomes.
The PhD student will investigate:
a) how microtubules capture and move kinetochores and;
b) how microtubules impart adequate forces to pull apart chromosomes into two equal sets.
The student will be trained in state-of-art high-resolution live-cell microscopy, biochemistry and molecular biology techniques.
A brief work plan is listed below:
- 1-15 months: The student will generate mutants of outer-kinetochore proteins that interact with microtubules. By expressing these mutants in human cells, the student will determine whether the mutant causes defective segregation of chromosomes.
- 15-30 months: The student will choose mutant phenotypes from year-1 for live-cell analysis for analysing changes in microtubule-mediated pulling of kinetochore and chromosome-microtubule attachment status.
- 30-36 months: The student will generate a written thesis of all successful experiments that help understand kinetochore structure and function.
This multi-disciplinary project is ideal for students interested in working at the interface of cancer and basic biology research.
Eligibility and applying
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, please email Professor Viji M. Draviam (firstname.lastname@example.org).
- 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).