Dentistry

Clinical PhD in Orthodontics

There are two Clinical PhD Studentships available in Orthodontics at the University of Dundee Dental School. 

Programme:

The Clinical PhD Studentships involve full-time study over five years for a PhD with simultaneous completion of the 4 year clinical residency resulting in eligibility to sit the Membership in Orthodontics examination at the Royal College of Surgeons of Edinburgh/Glasgow/London.

Research projects:

Development of an alternative alveolar bone graft for cleft lip and palate

Background: Patients presenting with clefts extending into the maxillary alveolar ridge, may be treated by bone grafts. Secondary alveolar bone grafts (ABG), regarded as the gold standard of ABG, were first introduced by Boyne and Sands 1972 (1) and are performed at the stage of mixed dentition (2). However, there are significant problems associated with the use of such grafts, mainly that a second surgical site is required which has its own morbidity associated. 

Identification of genes involved in F. nucleatum virulence & investigation of the response of eukaryotic cells to invasion

Background: The term ‘Periodontal disease’ is applied to a range of pathological changes to periodontal tissue. Our best understanding of this multi-factorial disease places a key role on microbial communities and central to these communities are Fusiform bacteria such as Fusobacterium nucleatum (FN). These long filamentous organisms are unparalleled in their ability to adhere to a range of different oral bacteria, and have been shown to invade epithelial cells (Edwards et al., 2006). Recent in vivo studies have also demonstrated invasion of the placenta and colon tumours.

Palatogenesis: Is there a Relationship between TGFβ3 and Hyaluronan Synthase Expression in vitro?

Project background: TGFβ3 plays an important role in palatogenesis and the corresponding homozygous null (-/-) mouse exhibits a defect in the fusion of the palatal shelves, resulting in clefting of the secondary palate. Palatal shelf elevation is considered to be driven by regional accumulation and hydration of glycosoaminoglycans, principally hyaluronan (HA). In vitro, addition of TGFβ3 to adult fibroblasts stimulates HA synthesis. HA is synthesised by three enzymes, Hyaluronan synthases (Has 1,2,3).

EGF and TGFα Motogenic activities are mediated by the EGF receptor: Identification of the signalling pathways involved in oral cancer

Background and Aims: Cells need to migrate away from their microenvironment to enable the tumour to metastasise. The growth factors Epidermal Growth Factor (EGF) and Transforming Growth Factor α (TGFα) stimulate the migration of fibroblasts into 3D collagen gels. Experiments using a number of growth factors concluded that some stimulated Akt phosphorylation whilst others reduced the phosphorylation of this pathway, but all stimulated migration; suggesting that multiple pathways are important for cell motility.

Is there a Role for Activated Akt in Palatogenesis?

Project background:  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. TGFβ-3 may signal via two pathways; SMAD pathway or 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, thus no palatal fusion is seen.

The interaction between the Growth Factor VEGF and the Signal Transduction Molecule Akt in Oral Cancer

Project Background: The growth factor VEGF and a signal transduction pathway protein, Akt, may have an important role in oral tumours. Oral cancer patients from Dundee have been shown to have an increased expression of VEGF both in their tissue and in their serum. It has also been reported that Akt is activated in response to growth factors and this activation may be blocked by inhibitors.

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