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• genetics, genomics and molecular biology
• cell and developmental biology/regenerative medicine

• General Practice
• Obstetrics and Gynaecology
• Pathology

• Clinical Trials
• Health Informatics
• Pharmacology
• Physiology

Research in my laboratory is focused on mechanisms of chromosome segregation in meiosis, the specialised cell division cycle that generates gametes (eggs and sperm). We are particularly interested in centromeres, key chromosomal loci upon which kinetochores assemble to orchestrate chromosome segregation with fidelity. Interestingly, centromeres are not determined by DNA sequence, instead centromeres are defined epigenetically at the protein level by the incorporation of a specialised histone variant called CENP-A. A major interest is to understand how CENP-A is inherited through cell division cycles in germ cells i.e. how is CENP-A chromatin replicated, assembled from new CENP-A molecules and maintained specifically at centromeres? To investigate such mechanisms, we use the fruit fly Drosophila melanogaster as a developmental model system. In this animal model, male and female reproductive tissues (testes and ovaries) are easily accessible and can be manipulated genetically. We combine genetics, biochemical and high-resolution imaging techniques to probe centromere dynamics in male and female germ cells (Dunleavy et al. 2012).

Dunleavy EM*, Beier NL*, Gorgescu W, Tang J, Costes SV, Karpen GH (2012) The cell cycle timing of centromeric chromatin assembly in Drosophila meiosis is distinct from mitosis yet requires CAL1 and CENP-C. PLoS Biol, 10(12): e1001460.

In my laboratory, we are interested understand the function of centromere proteins in meiosis, the specialised cell division cycle that gives rise to gametes (eggs and sperm). Currently, we investigate centromere function the fruit fly model system, but we are eager to corroborate our findings in humans. We have found that mutations in key centromere proteins e.g. CENP-C and CAL1 (called HJURP in humans) can lead to fertility defects or even sterility in flies (Kwenda et al. 2016). We are eager to explore potential correlations between mutations in centromere proteins, or changes in centromere RNA/protein expression, and fertility in human patient samples. In particular, we wish to determine if the key centromere proteins (CENP-A, CENP-C, HJURP) are present on mature sperm using cell biology or biochemical approaches. The PhD candidate would gain experience with molecular and cell biology, genetics, biochemistry and high-resolution fixed and time-lapse imaging.

Kwenda L, Collins CM, Dattoli AA, Dunleavy EM. (2016) Nucleolar activity and CENP-C regulate CENP-A and CAL1 availability for centromere assembly in meiosis. Development. Apr 14;143(8):1400-12.