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Is there a Role for Activated Akt in Palatogenesis?


Dental School

About the Project

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 ()
For general enquiries about the University of Dundee, contact


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 () 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 UCAS Postgraduate. When applying, please follow the instructions below:

Apply for the Doctor of Philosophy (PhD) degree in the Dental School. This project is suitable for a three-year PhD (application portal: https://digital.ucas.com/coursedisplay/courses/1e6f404e-f563-7944-91e8-2415b17a5347) or a four-year PhD (application portal: https://digital.ucas.com/coursedisplay/courses/979cf9ff-1542-9463-905b-1b48f16ec2da). Select the start date and study mode (full-time/part-time) agreed with the lead supervisor.

In the ‘provider questions’ section of the application form:
- Write the project title and ‘FindAPhD.com’ in the ‘if your application is in response to an advertisement’ box;
- Write the lead supervisor’s name and give brief details of your previous contact with them in the ‘previous contact with the University of Dundee’ box.

In the ‘personal statement’ section of the application form, outline your suitability for the project selected.

Funding Notes

There is no funding attached to this project. The successful applicant will be expected to provide the funding for tuition fees and living expenses, via external sponsorship or self-funding.

References

Brunet, Sharpe & Ferguson, (1995) International Journal of Developmental Biology, 39, 345-55.

Kang & Svoboda, (2002) Developmental Dynamics, 225, 316-21.

Extended list available on request

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