Bipolar spindle formation in mitosis and meiosis

Genes must be passed on accurately from cell to cell and from parents to children. During eukaryotic cell divisions, cells dramatically change their organisation. DNA carrying genes are packaged into chromosomes and the spindle made of microtubules is assembled to segregate the chromosomes. Two types of divisions, mitotic and meiotic, share common mechanisms but have critical differences including a lack of centrosomes.

The project aims to uncover how a bipolar spindle forms in oocytes which lack centrosomes, and how it differs from mitosis. The student will first determine the proteome of microtubule-associated proteins from Drosophila oocytes, using microtubule co-sedimentation followed by mass-spectrometry. This microtubule interactome of oocytes will be compared with that of early embryos which we previously identified. Oocyte specific microtubule-associated proteins will be prioritised for further study. To understand the functions, in vivo RNAi will be used to deplete the proteins in ovaries, and the spindle morphology and chromosome alignment will be examined in mature oocytes, both in fixed and live oocytes. Their localisation in oocytes will be determined, and molecular properties/activities will be established.

Finally, the student will test whether mutant phenotypes can be explained by molecular defects using computer simulation based on mathematical modelling. Furthermore, the model will be used to make a prediction which can be experimentally tested. Iterative experiment-modelling cycle will lead to better understanding of the spindle formation in oocytes.

During the course of PhD study, the student will use a combination of various approaches to tackle the question, which include genetics, biochemistry, bioinformatics, microscopy and mathematical modelling. The student will use their initiative to independently run their own project through close interaction with colleagues and the supervisor.