The role of the mitotic spindle assembly checkpoint (SAC) protein BUB3 in tumourigenesis. (360G-Wellcome-107414_Z_15_Z)

£446,052

The spindle assembly checkpoint (SAC) ensures the correct partition of chromosomes during mitosis. Depleting SAC proteins together with apoptosis inhibition leads to tumourigenesis. This project builds on a tumourigenesis model in Drosophila to address the role of SAC in hyperproliferation, metabolic regulation and tumour evolution. Initially I will study candidate genes uncovered by microarray analysis of a tumour generated by knocking down the SAC gene Bub3. As the cells' metabolic response ad apts to proliferation requirements it is clear that there must be a cross talk between cell cycle and metabolic control. To address this hypothesis, an enhancer/suppressor screen looking for metabolic proteins with links to cell cycle will be performed. The tumorigenic model derived from cell cycle defects affecting genomic integrity, will also be used to study tumour evolution. The use of a tumourigenesis fly model will exclude some difficulties of these studies in humans as tumours can be samp led at multiple stages. In addition, the tumour growth will not be limited by the life span of the hosts as the immortalized tumour can grow indefinitely through serial transplantations in inbred flies. Altogether the results will identify novel genomic loci and alterations responsible for tumour growth and cellular survival.

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Grant Details

Amount Awarded 446052
Applicant Surname Da Silva
Approval Committee Basic Science Interview Committee
Award Date 2015-04-13T00:00:00+00:00
Financial Year 2014/15
Grant Programme: Title Career Re-Entry Fellowship
Internal ID 107414/Z/15/Z
Lead Applicant Dr Sara Da Silva
Partnership Value 446052
Planned Dates: End Date 2022-03-18T00:00:00+00:00
Planned Dates: Start Date 2015-09-07T00:00:00+00:00
Recipient Org: Country United Kingdom
Region East of England
Sponsor(s) Prof Sarah Bray