Using a neural multicellular tumour spheroid model system this PhD studentship takes a multidisciplinary approach at addressing the influence of oxygen gradients, hypoxia and DNA mismatch repair on the fundamental processes of importance in tumour development.
Multicellular tumor spheroid (MCTS) cultures are excellent model systems for simulating the development and microenvironmental conditions of in vivo tumour growth. Many documented cell lines can generate differentiated MCTS when cultured in suspension or in a non-adhesive environment. While physiological and biochemical properties of MCTS have been extensively characterized, insight into the events and conditions responsible for initiation of these structures is lacking. MCTS are formed by only a small subpopulation of cells during surface-associated growth but the processes responsible for this differentiation are poorly understood and have not been previously studied experimentally. Analysis of gene expression within spheroids has provided clues but to date it is not known if the observed differences are a cause or consequence of MCTS growth. Two mechanisms associated with tumorigenesis are genetic instability (arising from impaired DNA mismatch repair) and hypoxia. This study aims to determine the role of MMR and hypoxia in a neural multicellular tumour spheroid model of tumour initiation and development.
This work is funded by a Gerald Kerkut Charitable Trust PhD studentship (2008-2011)
This work is supervised by Dr Jeremy Webb (SBS) and Dr Jeremy Blaydes (Cancer Sciences, SOM)