Characterise a novel DNA repair protein as a target for cancer therapies

Overview

Data generated in the lab has identified a novel DNA repair protein previously described as a key protein in HSP70/90 complexes. Many pathways of tumourigenesis are mediated by Heat Shock Proteins and HSP70/90 are found significantly upregulated in ovarian cancers. The targeting of HSP70/90 are an emerging therapeutic avenue for the treatment of ovarian cancer. Supporting this, an inhibitor of HSP90 has been shown to sensitise breast cancer cells to PARP inhibitors and paclitaxel.

Our preliminary data indicates that this new protein responds to DNA damage localising to DNA damage sites and is co-regulated with DNA repair proteins. In this project you will determine whether you can mediate the sensitivity of ovarian cancer cell lines to DNA damaging agents. To modulate the protein level you will silence expression with siRNA transfection or overexpress with plasmid transfections. You will then assess how this protein affects cancer cell response to common chemotherapeutic agents. Following this you will be able to further assess the target in patient samples with available patient derived xenograftand tissue microarrays this will provide clinical evidence supporting your findings.

This will demonstrate that the modulation of expression of a novel could be a viable treatment option for cancer patients

Approaches, skills and techniques

• Cancer cell line culture.
• Bioinformatic analysis.
• Cancer cell line chemotherapeutic treatment.
• Understanding of cellular signalling.
• Western blot and immunofluorescence protein quantification.

Outcome

This proposal presents an opportunity to provide foundations for the development of new cancer therapies. At the end of this proposal you will have defined the prognostic significance of a novel DNA repair protein.

Keywords

• DNA Repair
• Cancer Therapies

Contact

Contact the supervisor for more information.