Is there a Role for Activated Akt in Palatogenesis?

Main Aim

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.

For informal enquiries about the project, contact Dr Sarah Jones (s.j.jones@dundee.ac.uk)

For general enquiries about the University of Dundee, contact doctoralacademy@dundee.ac.uk

Our research community thrives on the diversity of students and staff, which helps make the University of Dundee a UK university of choice for postgraduate research. We welcome applications from all talented individuals and are committed to widening access to those who have the ability and potential to benefit from higher education.

QUALIFICATIONS

Applicants must have obtained, or expect to obtain, a first or 2.1 UK honours degree, or equivalent for degrees obtained outside the UK in a relevant discipline.

English language requirement: IELTS (Academic) score must be at least 6.5 (with not less than 5.5 in each of the four components). Other, equivalent qualifications will be accepted. Full details of the University’s English language requirements are available online: http://www.dundee.ac.uk/guides/english-language-requirements.

APPLICATION PROCESS

Step 1: Email Dr Sarah Jones (s.j.jones@dundee.ac.uk) to (1) send a copy of your CV and (2) discuss your potential application and any practicalities (e.g. suitable start date).

Step 2: After discussion with Dr Jones, formal applications can be made via our direct application system. When applying, please follow the instructions below:

1. Apply for the Doctor of Philosophy (PhD) degree in Dentistry (non-clinical): Dentistry research degrees | University of Dundee.
2. Please select the study mode (full-time/part-time) and start date agreed with the lead supervisor.
3. In the ‘personal statement’ section, please outline your suitability for the project selected.
4. In the Research Proposal section, please:

• Enter the lead supervisor’s name in the ‘proposed supervisor’ box
• Enter the project title listed at the top of this page in the ‘proposed project title’ box