Funded PhD: Cyclin-dependent kinase inhibitors as a novel treatment option for glioblastoma patients

This project aims to assess the clinical applicability of cyclin-dependent kinase inhibitors (CKIs) as a novel treatment option for glioblastoma (GBM) patients.

  • Principal investigator(s) Brona Murphy
  • Research theme Cancer

Project description

Brain tumours are the biggest cancer killer of children and adults under 40. Brain tumours reduce life expectancy by an average of 20 years, the highest of any cancer. Survival rates have improved little in over 40 years.

GBM is the most common and aggressive primary brain tumour. Despite intense efforts to combat GBM with surgery, radiation and chemotherapy, 90–95% of patients succumb to the disease within five years of diagnosis and almost all patients experience disease recurrence, usually within 6–8 months of treatment onset. It is essential that new, better, more-targeted treatments are properly assessed in robust brain tumour models.

This research proposal, built on a solid foundation of published work [1–4 below], aims to assess the clinical applicability of CKIs as a novel treatment option for GBM patients. By combining, 3D cultures, cancer stem cell populations, large scale high-content screening, light-sheet fluorescence microscopy, transcriptomic profiling and in vivo studies using PDX models, this integrative translational project will comprehensively examine the therapeutic potential of CDK inhibitors as a treatment strategy for GBM patients.

Tenure: Four years

Expected start date: December 2021/January 2022 

Specification

Minimum requirements:

  • Minimum upper second class (2.1) honours degree (or equivalent) in in biochemistry, molecular biology, biotechnology or similar 

Desirable candidate specifications include:

  • Masters and/or diploma or other higher degree qualifications
  • Wet lab techniques including
    • Cell culture
    • Western blotting
    • Microscopy
    • Experience in establishing new assays/techniques in the lab

Application process

To apply, please complete the online application form in full.

Applications must include:

Deadline: 12 November 2021 at 17:00

Please note:

  • Unfortunately, we are unable to provide individual feedback to applicants.
  • Shortlisted candidates will be invited for interview.
  • At this stage only successful candidates will be contacted to submit transcripts and other relevant documentation.
  • Only their referees will also be contacted at this stage for a reference.
  • It is the candidate's responsibility to ensure the application is completed in full on time. Late and/or incomplete applications will not normally be assessed.

1. Noonan, J.J., et al., 'Implementing Patient-Derived Xenografts to Assess the Effectiveness of Cyclin-Dependent Kinase Inhibitors in Glioblastoma.' Cancers (Basel), 2019. 11(12)

2. Juric, V., et al., 'Transcriptional CDK Inhibitors CYC065 and THZ1 Induce Apoptosis in Glioma Stem Cells Derived from Recurrent GBM.' Cells, 2021. 10(5)

3. Juric, V., et al., 'Transcriptional CDK inhibitors, CYC065 and THZ1 promote Bim-dependent apoptosis in primary and recurrent GBM through cell cycle arrest and Mcl-1 downregulation.' Cell Death Dis, 2021. 12(8): p. 763

4. Murphy, A.C., et al., 'Modulation of Mcl-1 sensitizes glioblastoma to TRAIL-induced apoptosis'. Apoptosis, 2014. 19(4): p. 629-42