DISSECTING ACTIN-DEPENDENT CHROMOSOME COHESION IN MAMMALIAN OOCYTES (360G-Wellcome-212503_Z_18_Z)

£100,000

When immature oocytes develop into eggs, a specialised form of cell division called meiosis segregates the chromosomes. Meiotic chromosome segregation errors are remarkably common and can give rise to aneuploidy, a leading cause of human embryo deaths and genetic disorders such as Down’s syndrome. I recently showed that accurate chromosome segregation in mammalian eggs critically relies on actin (Mogessie and Schuh, Science, 2017). I have now obtained data that suggest a previously unknown function of actin in chromosome cohesion, a mechanism that prevents untimely separation of chromosomes. It is known that loss of chromosome cohesion underlies aneuploidy in human and mouse oocytes. Actin-dependent chromosome linking is therefore a novel finding that deserves detailed investigation. Here, I will address actin-dependent cohesion in mouse oocytes by combining advanced microscopy techniques with drug-based loss-of-function assays. I will further dissect this novel mechanism by restricting loss-of-function assays to meiotic chromosomes and their kinetochores. Ultimately, I will examine whether actin can be used to bolster weakened cohesion and prevent aneuploidy in oocytes. Findings from this study will define a new ‘chromosome gluing’ mechanism that can potentially be repurposed to prevent aneuploidy in oocytes of fertility treatment patients.

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Grant Details

Amount Awarded 100000
Applicant Surname Mogessie
Approval Committee Science Seeds Advisory Panel
Award Date 2018-05-21T00:00:00+00:00
Financial Year 2017/18
Grant Programme: Title Seed Award in Science
Internal ID 212503/Z/18/Z
Lead Applicant Dr Binyam Mogessie
Partnership Value 100000
Planned Dates: End Date 2018-12-31T00:00:00+00:00
Planned Dates: Start Date 2018-06-25T00:00:00+00:00
Recipient Org: Country United Kingdom
Region South West