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Studies of highly prevalent prostate diseases, such as benign prostatic hyperplasia and prostate cancer, are compromised by the lack of clinically relevant models using human prostate tissue. Although primary culture models exist, they are hampered by the small number of cells that can be cultured, viability beyond 2-4 weeks and altered phenotypes. A potential solution is the use of adult cells reprogrammed into embryonic stem cells (ESCs), called induced pluripotent stem cells (iPSCs), which offer a theoretical limitless supply of cells that can be differentiated into prostate cells. Generation of tissue-specific iPSCs is important, as iPSCs show preferential differentiation into the lineages from which they were derived because of methylation imprinting from the parent somatic cell. Our laboratory is the first to generate human prostate iPSCs, using an Oct4-Sox2-Klf4-cMyc polycistronic lentivirus, and we have shown that an early prostate-like phenotype can be regenerated. Of note, iPSCs derived from skin was unable to differentiate into mature prostate cells. These findings confirm prostate iPSC generation, but the full extent of prostate differentiation requires further characterisation.
In this study we will assess if human prostate derived iPSCs can regenerate fully differentiated prostate-like glands in vivo. This will involve the introduction of differentiation and lineage specific fluorescent markers to allow tracing of prostate iPSCs differentiation. Characterisation of this prostate stem cell differentiation model will provide new insights into the mechanisms of prostate disease.
Funding Notes:
Sponsor: MRC (www.mrc.ac.uk)
Value of the Award and Eligibility: Depending on how you meet the MRC’s eligibility criteria, you may be entitled to a full or a partial award. A full award covers tuition fees at the UK/EU rate and an annual stipend of £13,590 (2012/13). A partial award covers fees at the UK/EU rate only.
References:
Person Specification: Candidates must have a BSc (Hons) in an appropriate scientific speciality at either a first or 2:1 level or a Masters degree (Merit or Distinction) in a relevant subject.
You must complete the University's postgraduate application form - http://www.ncl.ac.uk/postgraduate/apply/. Select "Master of Research/Doctor of Philosophy (Medical Sciences) – cancer research” as the programme of study. Only mandatory fields need to be completed (no personal statement required) but you must attach a copy of your CV and a covering letter, quoting the title of the studentship and reference number CR059.