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