Dr Vicky Cowling, Prof Steven Pollard, Dr Joanna Birch
Project Description
How can we target RNA modifications in brain cancers?
Glioblastoma cell proliferation and migration in the brain is largely controlled by which proteins they express. We investigate how gene expression is controlled in glioblastoma cells with the aim of developing therapeutic strategies to target the proteins which control cell proliferation and migration. Our focus is on a structure called the RNA cap, a modification which selects specific RNAs for processing and translation into protein. In neural stem cells, the enzymes which form the RNA cap have a specific configuration which directs gene expression, thereby defining cell identity and promoting proliferation. In this project, the student will investigate how the RNA capping enzymes are configured in glioblastoma cell lines, which have features common with neural stem cells. Mass spectrometry will be used to characterise RNA capping enzymes post-translational modifications and interacting proteins. Biochemical assays will be used to determine the function of novel enzyme configurations. The RNAs which interact with the RNA capping enzymes will be determined using RNA sequencing approaches. The RNA capping enzyme expression and activity will be altered using genome editing and other techniques to experimentally alter these enzymes. The impact of the RNA capping enzymes on gene expression, cell proliferation and cell migration will be analysed in tissue culture and in vivo. Enzyme assays, RNA sequencing methods and mass spectrometry will be used to define the impact of RNA cap regulation in glioblastoma. The student will be supported by postdoctoral researchers in the Cowling, Birch and Pollard labs who have expertise in neural stem cell and glioblastoma cell culture and in gene expression assays. Training will be provided in all experimental techniques, including bioinformatics analysis. The student will also explore the potential drug discovery aspects of their research, via interactions with the host labs and Cancer Research Horizons.
Training offered
- Advances Tissue culture: Culture and differentiation of primary murine neurons, iPS-derived neuronal lines, human glioblastoma multiforma (GBM) cell lines
- In vivo analysis: neuron and GBM proliferation and migration
- Molecular Biology: RNA-protein interaction analysis (CLIP-ART, CLAE)
- Transcriptome analysis: advanced RNA sequencing methods
- Biochemistry training: enzyme assays, chromatography, protein complex analysis (mass spectrometry)
- Bioinformatics analysis: transcriptome analysis, protein structure modelling
For further information on the project or informal enquiries, please contact Prof Vicky Cowling, This email address is being protected from spambots. You need JavaScript enabled to view it.
To place an application, please visit this site at the University of Glasgow.
When submitting your application please upload the completed recruitment form.
Lab Websites
Prof Vicky Cowling
Prof Steven Pollard
Dr Joanna Birch
Papers of interest
mRNA cap methylation in pluripotency and differentiation - https://www.sciencedirect.com/science/article/pii/s2211124716308580
CMTR1 is recruited to transcription start sites and promotes ribosomal protein and histone gene expression - https://academic.oup.com/nar/article/50/5/2905/6536890
Glioblastomas acquire myeloid-affiliated transcriptional programs via epigenetic immunoediting to elicit immune evasion - https://pubmed.ncbi.nlm.nih.gov/33857425/
Inhibition of ATR opposes glioblastoma invasion through disruption of cytoskeletal networks and integrin internalisation via macropinocytosis - https://pubmed.ncbi.nlm.nih.gov/37936324/