Human PDE4D7 as a risk factor for patient stratification in Prostate cancer

Medical Research Council (MRC) Doctoral Training Programme (DTP) Studentships

Positions are available in the College of Medical Veterinary, Medical and Life Sciences associated with MRC/CSO Social & Public Health Sciences Unit and MRC Centre for Virus Research. Our next intake will be for PhD projects commencing October 2017. The MRC DTP offers PhD with Integrated Study studentships funded by the MRC.

This DTP focuses on training PhD students in key MRC skills priorities in quantitative skills (mathematics, statistics, computation, and developing digital excellence) as applied to variety of data sources (from ‘omics’ to health records), and interdisciplinary skills including imaging and stratified medicine.

ALL PROJECTS CAN BE VIEWED HERE: http://www.gla.ac.uk/colleges/mvls/graduateschool/mrcdtpstudentships2017/projects/ - NOTE: DETAIL WITHIN STEP 6 OF APPLICATION PROCESS THE SUPERVISOR AND PROJECT TITLE.

Supervisors
Prof George Baillie - [Email Address Removed]
Prof Philippa Saunders - [Email Address Removed]
Dr Ralf Hoffmann - [Email Address Removed]

Abstract
We have been working the last years on the clinical validation of the prostate cancer biomarker PDE4D7 which is one the long isoforms of the cAMP phosphodiesterase 4D family (Henderson et al. Br J Cancer, 2014). The expression of PDE4D7 is correlated with prostate cancer aggressiveness as well as disease progression as demonstrated on multiple data clinical sets with longitudinal outcome data (Boettcher et al. Br J Cancer, 2015).

In order to define a new mechanism in prostate cancer progression we have identified a novel binding partner for PDE4D7called DHX9. To identify genomic interaction sites for DHX9 in prostate cancer cells DHX9-ChIP-Seq (Chromatin Immunoprecipitation Sequencing) experiments will be performed in collaboration with Edinburgh University. This will be done in different types of prostate cancer cell lines and human xenograft samples representing various stages of the human disease. After NGS sequencing of the precipitated DNA fragments genome wide mapping of sequencing reads will be done to identify gene candidates potentially interacting with DHX9. Interaction candidates will be verified by PCR approaches. GSEA (gene set enrichment analysis) will reveal enriched molecular pathways. Binding sites between DHX9 and candidates genes will be determined and we will test whether the expression level of PDE4D7 has any influence on this interaction and consequently a down-stream effect on the transcription of the candidate gene(s).