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Sara Morais da Silva PhD

Cross-talk between cell cycle proteins and metabolic pathways.
Sara  Morais da Silva, PhD

Senior Research Associate

Wellcome Trust Research Career Re-entry Fellow

Office Phone: +44 (0) 1223 333755

Research Interests

The similarities between Drosophila and the human cell cycle machinery, cellular processes and regulatory pathways make Drosophila an excellent model in which to study the link between the cell cycle and tumorigenesis, given the powerful genetic strategies that can be employed with this organism. The spindle assembly checkpoint (SAC) proteins ensure a correct chromosomal distribution between cells during mitosis. In Drosophila, an impaired SAC together with cell death prevention results in hyperproliferation and tumour growth. As the metabolic response of the cells adapts to proliferation requirements it is clear that there must be a cross talk between cell cycle and metabolic control. Therefore Drosophila genetics will be used to uncover the links between cell cycle, in particular the SAC proteins and cellular metabolism by looking for phenotype alterations in tumour growth.

Main source of funding: Wellcome Trust

Key Publications

Morais da Silva S, Moutinho-Santos T, Sunkel CE, (2013), A tumor suppressor role of the Bub3 spindle checkpoint protein after apoptosis inhibition, J Cell Biol, 201(3):385-93. doi: 10.1083/jcb.201210018

da Silva SM, Vincent JP (2007), Oriented cell divisions in the extending germband of Drosophila, Development, 134(17):3049-54

da Silva SM, Gates PB, Brockes JP, (2002), The newt ortholog of CD59 is implicated in proximodistal identity during amphibian limb regeneration, Dev Cell, 3(4):547-55

Morais da Silva S, Gates PB, Eib DW, Martens GJ, Brockes JP, (2001), The expression pattern of tomoregulin-1 in urodele limb regeneration and mouse limb development, Mech Dev, 104(1-2):125-8

Morais da Silva S, Hacker A, Harley V, Goodfellow P, Swain A, Lovell-Badge R, (1996), Sox9 expression during gonadal development implies a conserved role for the gene in testis differentiation in mammals and birds, Nat Genet, 14(1):62-8

Above: Knockdown of the SAC gene Bub3 promotes tumorigenesis in Drosophila wing discs. (A) Diagramme of larvae imaginal discs and their resulting adult structures. 1.eye-antena disc; 2. Wing disc; 3. Haltere disc; 4. Clypeolabral disc; 5. 1st leg disc; 6. 2nd leg disc; 7. 3rd leg disc. (B) GFP expression in the wing imaginal disc. (B') Wing disc dissected out of a L3 larvae where Bub3 was knocked-down with RNAi and cell death inhibited with P35. Note the hyperplasia. (C, C') Larvae expressing GFP (upper) and expressing Bub3 RNAi, p35 and GFP (lower).(J) Hyperplastic discs were implanted into adult female hosts to assess their proliferative potential. Discs expressing GFP and p35 and Bub3 RNAi were implanted. Note that the implants grew extensively in the Bub3 RNAi p35 discs invading the host abdomen. Bars, 40 μm (B); 80 μm (B').