About the Project
Neuroendocrine cells act as an interface between the nervous and endocrine systems, releasing hormones into the blood as a result of neuronal signals. Tumours arising in these cells are designated neuroendocrine tumours (NETs). NETs can be benign or malignant and occur in multiple organs including the pituitary (Thakker, et al. 2012). Pituitary tumours are common and represent the most frequently encountered intracranial tumours, with the majority (>65%) secreting excessive hormones (e.g. prolactin, growth hormone, adrenocorticotropic hormone, and thyroid stimulating hormone) that result in specific endocrine symptoms e.g. excessive growth, and are referred to as functional. The remaining ~35% do not secrete hormones (called non-functioning), meaning they escape early detection, and can therefore be much larger at diagnosis and may cause e.g. vision defects. Pituitary tumours occur as part of a hereditary (i.e. familial) disorder, or as non-familial (i.e. sporadic) disease (Yates, et al. 2014), however despite a number of causative genes being identified, including MEN1 and AIP, the genetic mechanisms underlying the causes for the majority (>60%) of pituitary tumours remain to be elucidated
Our group has previously performed whole exome sequencing on multiple individuals with non-functioning pituitary tumours (Newey, et al. 2013), however this did not identify a key gene involved in driving pituitary tumour development. The analysis has therefore been extended to performing whole genome sequencing on multiple individuals, as well as families with pituitary tumours, to identify novel genetic mutations that may be causing pituitary tumour development. This analysis has identified over 400 candidate genes with mutations.
The objective of this DPhil project is therefore to select and characterise the function of the identified mutations from our whole genome sequencing, and determine the mechanisms by which they may contribute to tumourigenesis. The student will assess the effects of the mutation both in vitro using cell lines, and by developing in vivo models, using methods similar to those previously described (Gorvin, et al. 2014; Lines, et al. 2016; Newey et al. 2013), with the aim of gaining greater insight into the genes and pathways involved in pituitary tumourigenesis, which is important for correct diagnosis and treatment.
Funding Notes
Funding for this project is available to basic scientists through the RDM Scholars Programme, which offers funding to outstanding candidates from any country. Successful candidates will have all tuition and college fees paid and will receive a stipend of £18,000 per annum.
For October 2017 entry, the application deadline is 6th January 2017 at 12 noon (midday).
Please visit our website for more information on how to apply.