PhD in Cancer Genetics, funded by Sêr Cymru (PhD Studentship)
Reference Number: R2317
Project title: Developing novel reagents to target the DNA damage signal associated with Wnt activated Colorectal cancer
Deregulation of Wnt signaling is a key event in colon cancer. This studentship will pursue the hypothesis that there is a ‘just right’ level of Wnt signaling that is consistent with successful adenoma growth, and that levels of Wnt activity higher than this are actually refractory to tumour growth.
We know that acute activation of the Wnt pathway leads to high levels of DNA damage and high levels of apoptosis. We have also previously shown that excess Wnt activity can restrict adenoma formation because of hyper-activation of acute apoptosis. Taken together, these observations suggest that the DNA damage observed immediately after Wnt activation might offer a therapeutic opportunity if it can be manipulated to increase levels of apoptosis.
We will therefore now explore the possibility of using the ?H2AX damage signal to ablate Wnt deregulated cells and so repress tumorigenesis. ?H2AX is generally known as a marker of DNA double strand break damage, and is expressed in foci of several thousands of copies around sites of DNA double strand breaks.
Our collaborator, Bart Cornelissen at Oxford University, have demonstrated that ?H2AX can be used as a marker to visualize and quantify the extent of DNA damage in tumours in vivo, in living animals, after genotoxic insults such as gamma-irradiation or chemotherapy (Cornelissen et al, 2011). In this project we will investigate the use of 111In-labeled anti-?H2AX-Tat as a radionuclide therapy agent after Wnt activation induced expression of ?H2AX in precancerous lesions in the gastro-intestinal system. Our hypothesis is that 111In-anti-?H2AX-Tat treatment will suppress Wnt driven tumorigenesis.
Start date: 1 October 2014
Number of Studentships: 1
This studentship is generously funded by Sêr Cymru. It consists of full UK/EU tuition fees, as well as a Doctoral Stipend matching UK Research Council National Minimum (£13,863 p.a. for 2014/15, updated each year).
One studentship is available.
Residency: Full awards (fees plus maintenance stipend) are open to UK Nationals and EU students without further restrictions.
Academic criteria: Applicants for a studentship must have obtained, or be about to obtain, a first class or 2.1 degree in biomedical sciences, and/or a Master's degree in a relevant field.
How to Apply
Consideration is automatic on applying for Doctor of Philosophy (Biosciences), with a start date of October 2014 via Cardiff University's Online Application Service. In the research proposal section of your application, please specify the project title and supervisors of this project and copy the project description in the text box provided. In the funding section, please select "I will be applying for a scholarship / grant" and specify that you are applying for advertised funding from Ser Cymru.
The deadline for applications is 10 August 2014.
Cardiff University reserves the right to close applications early should sufficient applications be received.
General information on research within the School of Biosciences can be found via the research pages of the School website.
Further information about the Sêr Cymru programme can be found here.
References: Cornelissen B, Darbar S, Kersemans V, Allen D, Falzone N, Barbeau J, Smart S, Vallis KA. Amplification of DNA damage by a ?H2AX-targeted radiopharmaceutical. Nucl Med Biol. 2012 Nov;39(8):1142-51. doi: 10.1016/j.nucmedbio.2012.06.001. Epub 2012 Jul 18. PubMed PMID: 22819196.