Is there a Role for Activated Akt in Palatogenesis?
28 February 2024
About the project
The project will use a medial edge epithelial (MEE) cell line as an in vitro model. These cells will be used to investigate the effects of exogenous TGFβ-3 and activation of Akt on cell migration, epithelial to mesenchymal transition (EMT) and apoptosis. The resultant data will enable a deeper understanding of the role of TGFβ-3 and the fate of the midline epithelial seam during palatal fusion.
TGF-β3 plays an important role in palatogenesis. The TGFβ-3 homozygous null (-/-) mouse has a cleft palate and treatment of palatal shelves from these knockout mice, ex vivo, with TGFβ-3 causes the palatal shelves to fuse (Brunet et al., 1995). TGFβ-3 may signal via two pathways; the SMAD pathway or the PI-3 kinase/Akt pathway. Blocking of the PI-3 kinase pathway by the inhibitor LY294002 causes the medial edge epithelium to persist in the midline and the basal lamina to remain intact (Kang and Svoboda, 2002), thus no palatal fusion is seen. Epithelial cells of the midline are seen to disappear after fusion and one of the proposed mechanisms for this is epithelial-mesenchymal transition (EMT) which requires PI-3 kinase activity (Kang and Svoboda, 2002). Other possible mechanisms include cell migration and apoptosis. The project will also look for evidence of these events using scratch assays for cell migration and immunocytochemistry with the PAPR-1 antibody for apoptosis.
How to apply
- Email Dr Sarah Jones (email@example.com) to:
- send a copy of your CV
- discuss your potential application and any practicalities (e.g. suitable start date)
- After discussion with Dr Jones, formal applications can be made via our direct application system.