Institute of Cancer Genetics 3 year PhD studentship: Pre-clinical cancer studies targeting cellular homeostasis (PhD Studentship)
Reference Number: R871
Key Studentship Information
Project Title: Targeting endoplasmic reticulum stress and autophagy in cancer
This research project is designed to function within a translatable research pipeline led by Prof. Julian Sampson within the well established Medical Genetics Department at Cardiff University will give a solid foundation for a PhD student to carry out this cancer research project. The PhD student will receive day-to-day supervision in the laboratory and weekly project meetings. This is a 3 year research project, where the Ph.D student will become an active member of Dr Andrew Tee’s research team currently consisting of 2 post-docs and 4 PhD students.
The progress of the work would also be discussed in lab meeting as well as shared meeting with other members within cancer genetics. This research group has an excellent track record in human genetic disease research. Collective research from this group has enabled the inception of a translational clinical trial that is co-ordinated through the clinical arm of the research group in tuberous sclerosis (headed by Prof Sampson and Dr Mark Davies). Dr Tee’s lab has the experience and reagents to enable biochemical dissection of the selected cell signalling pathways in this project.
The main focus of this project is to carry out pre-clinical investigations that will support cancer therapy trials. We have made contributions to the understanding of the cellular events: that the Tuberous Sclerosis Complex (TSC) proteins block tumour growth by inhibiting molecular events involving mammalian Target of Rapamycin (mTOR). mTOR plays a broad role in cancer progression being involved in many cellular processes, including protein synthesis, cell cycle progression, cell growth, gene expression, autophagy (recycling of cellular components), mitochondrial biogenesis/glycolysis (cellular energy production), apoptosis (controlled cellular death), angiogenesis (hypoxia-mediated blood vessel growth) and nutrient uptake. Heightened activity of mTOR within cells contributes to the adverse cellular pathology of tumours. Indeed, mTOR is centrally involved in a number of inherited hamartoma syndromes, which includes TSC, Cowden's disease, Neurofibromatosis, Birt-Hogg Dube and Peutz-Jeghers syndrome. These syndromes occur through the loss of function of tumour suppressor proteins that consequentially leads to heightened activity of mTOR and tumour growth.
Project Description:
Autophagy is critically involved in maintaining cells (also known as cellular homeostasis). The focus of the project is to utilise clinically viable drugs to disrupt cellular homeostasis of cancer cells. We will systematically evaluate critical cell processes that are modulated by mTOR involved in cancer cell growth and cancer survival. You will be strategically part of a translational research team at
Abnormal cellular stress is a hallmark of cancer. This can be exploited to selectively kill tumour cells by exacerbating existing stress or by inhibiting stress response pathways. The endoplasmic reticulum (ER) is involved in the folding and processing of proteins. Disruption of ER homeostasis results in ER stress which if severe results in cell death Induction of ER stress leads to upregulation of autophagy which may act as a prosurvival mechanism. Mutations in components of the PI3K/mTOR pathway have been implicated in sporadic cancer and tumour predisposition syndromes. Mutations in these genes may also impair ER homeostasis and autophagy. We plan to assess the effects of ER stress inducing agents and autophagy inhibitors in cells with mutations in components of the PI3K/mTOR pathway in vitro and in vivo.
You will be strategically part of a translational research team at
Supervisors: Prof Julian Sampson, Dr Mark Davies, Dr Andrew Tee
Funding
This funding award is part funded by the school and a generous contribution from the Welsh Gene Park.
Successful applicants will receive an award covering UK/EU tuition fees plus a Doctoral Stipend matching UK Research Council National Minimum (£13,590 p.a. for 2011/12, updated each year).
Students from outside of the EU are welcome to apply but will not be eligible for an award covering the full international tuition fees. Succesful international applicants will recieve support amounting to the UK/EU tuition fee level and must fund the remainder of the international fees from another source.
Start Date: 1st October 2012
Eligibility
Academic Criteria: The ideal applicants would hold a 1st class BSc in a Life Science discipline. Succesful graduates holding a 2:1 degree will also be considered for the position.
Residency: Full awards (fees plus maintenance stipend) are open to UK Nationals, and EU and international students who can satisfy
How to Apply
In the first instance, applicants should send a CV and covering letter to ICG-Admin@cardiff.ac.uk.
Application Deadline: 15th August 2012
Further Information
For more information please contact:
Email: ICG-Admin@cardiff.ac.uk
Tel: +44 (0)2920 687856
Or visit the School of Medicine's website for more details on research opportunities.
