Project Title: Investigating the Potential of Oral Progenitor Cell Populations for the Treatment of Chronic Disease
Project Description: Stem cells hold much promise for the repair and regeneration of damaged and diseased tissues. Our recent work has resulted in the isolation of a novel, stem cell population from the oral mucosa. We have demonstrated that oral mucosal progenitor cells (OMLP-PCs) are both multi-potent and actively immunosuppressive suggesting that they may be beneficial in both tissue engineering applications and directly in the treatment of immune related disorders. This PhD project will further investigate the properties of these OMLP-PCs, focussing on their potential for the treatment of immune related and infectious diseases.
This project will contribute to our growing portfolio of Research Council funded stem cell projects and our international patent filings regarding the isolation and characterisation of OMLP-PCs. This project sits firmly with ongoing research projects in both the Wound Biology Group (P. Stephens and L. Davies) and Mineralised Tissue Group (A. Sloan), meaning that the student will be well supported by numerous postdoctoral researchers and postgraduate students already working in the field of stem cell biology. Both groups are well funded (Research Council funding) and resourced. The student will also be supported in the laboratory by a recently appointed technician who will provide half-time lab support for research in this area.
The student will have an opportunity to develop a wide range of laboratory technical skills during the project (e.g. tissue culture, microbiology) allowing the development of extensive cross disciplinary technical skills equipping the student well for their future career. As the project develops there will also be the opportunity to develop knowledge in both protein and molecular biology, with the student learning RT-PCR, siRNA and electrophoretic techniques such as SDS-PAGE/Western Blotting and proteomics.
Supervisors: Professor Phil Stephens, Dr Lindsay Davies and Dr Alastair Sloan
Project Title: Elucidating novel roles for extracellular matrix proteins in directing stem cell biology
Project Description: Understanding the factors regulating stem cell proliferation and differentiation of injured tissue are basic biological concerns for their successful clinical application in bone and dentine tissue engineering. Whilst growth factors are recognised to provide a prime regulatory role, other extracellular proteins are now becoming recognised as important in modulating cell signalling and providing roles in directing angiogenesis, bone and dentine formation. The aim of this studentship project is to identify and characterise the biological activity of novel extracellular matrix components which may function to aid growth factor signalling of progenitor cells in mineralised tissue repair. The project will involve the fractionation and biochemical characterisation of a range of proteins previously considered as structural components of mineralised tissues. Emphasis of the project will be placed on examining the influence of these components on the behaviour and cell signalling events of mesenchymal stem cells and furthering our understanding of the vital cell signalling roles of the matrix components. The outcomes will support clinical development of novel materials, with a defined protein composition, which enhance bone and dentine repair. The successful applicant will join a team of researchers based in the School of Dentistry with a research focus of elucidating the role of mesenchymal stem cells in the formation of mineralised tissues and how the extracellular environment can be harnessed to enhance tissue engineering approaches through better mimicking of the natural repair processes.
Supervisors: Professor Rachel Waddington and Dr Alastair Sloan
Project Title: Dynamics of dental plaque biofilms in intensive care patients
Project Description: The composition of the oral microflora of individuals in intensive care changes significantly with an increase in the numbers of opportunistic pathogens such as MRSA and aerobic and facultatively anaerobic Gram-negative bacilli. These bacteria cause the vast majority of hospital-acquired infections and are associated with multidrug resistance. Despite the importance of the oral cavity and oropharynx as reservoirs for such organisms, little attention has been given to the mechanisms underlying the altered dynamics of this microflora. Changes in the oral microflora are known to occur with environmental conditions and in the case of patients admitted to intensive care, it has been suggested that the dental plaque changes to one dominated by potential respiratory pathogens such as Pseudomonas aeruginosa and Staphylococcus aureus. The aims of this research are to investigate microbial changes within the oral cavity of intensive care patients, the underlying causes for these and approaches that can prevent them. Results can be used to aid management of respiratory infection by providing early detection of pathogens and in a manner avoiding invasive sampling of the lower airway, as currently practiced. The study will monitor microbial composition of dental plaque and lower airways of intensive care patients using traditional culture and metagenomic analysis. Saliva will also be collected over the sampling period and analysed for flow, pH and proteomic content. Changes in these parameters will be correlated against microbial population shifts and tested using a mixed species biofilm endotracheal/oropharyngeal model. In addition, the model will be used to examine the effect of two main interventional strategies; firstly, the influence of topically applied antimicrobials (oropharyngeal chlorhexidine application has been shown to reduce incidence of VAP in ITU patients); and secondly, the effect of lytic bacteriophages targeted at specific organisms (phage therapy has been used with increasing success in many clinical decontamination scenarios).
Supervisors: Dr David Williams, Dr Melanie Wilson, Professor Mike Lewis and Dr Matt Wise
The deadline date for all three Studentships is 11 May 2012. Start date is 1 October 2012.
Mrs Victoria J Ocock
Admissions, Enrolment and Graduation Officer
Tel: 029 20746917