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Validation of novel biomarkers for improved risk stratification and therapy for the paediatric cancer neuroblastoma


Project Description

Neuroblastoma is the second most common cancer in childhood but still has one of the lowest survival rates of all childhood malignancies. Since 2008, clinicians have been using a patient risk group classification to inform the choice of therapeutic intervention. However, there are still groups of patients wrongly classified as low or intermediate risk, who end up with the wrong treatment and consequently have poor survival or unnecessary side-effects. Here, we propose to validate new markers that will better classify patients, thereby optimising treatment options. We have recently discovered potential new markers by comparing the genes active in aggressive neuroblastoma tumours, which spread throughout the body, and in tumours that are not able to spread, using an in vivo chick embryo model. Using patient databases, we found that 9 out 10 of our top regulated genes act as excellent prognostic markers. However, in clinical practice, gene expression levels are rarely assessed in tumour tissues, instead protein levels are measured. We will therefore select the most promising genes for risk stratification and study their protein expression in neuroblastoma tumours. We will initially measure protein expression in tumours formed in the chick embryo (metastatic compared to non-metastatic) and then investigate the most promising protein biomarkers in patient tissues. We will analyse their expression as a function of patient outcome. We will further elucidate the molecular mechanisms, which can explain their altered expression. This knowledge will allow us to manipulate expression of these biomarkers, providing avenues for further therapeutic intervention.

The project will involve proteomic analysis of the biomarker candidates using Multiple Reaction Monitoring Mass Spectrometry in collaboration with the centre for proteome research, manipulation of the chick embryo model to study tumorigenesis and perform drug testing, immunostaining and imaging of the tumours and functional analysis of drug efficacy by measuring cell proliferation, apoptosis, cell differentiation, gene expression… It is a multidisciplinary project with clinicians, who will provide access to tumour samples and biobank.

The training will include a range of techniques such as basic molecular and cell biology techniques including molecular cloning, tissue culture, the chick embryo model, protein and mRNA expression measurements, cell survival assay and gene expression. In addition, the student will also receive a strong training in proteomic and microscopy within the Liverpool Centres for Proteome research and for Cell Imaging. The supervisory team, which includes scientists and clinicians will closely mentor and train the students whilst providing the opportunity to develop their own ideas. The student will also be trained in scientific communication skills by presenting their work at lab meetings, international conferences and during poster presentations.

Funding Notes

Open to both UK/International students with their own funding/scholarship. Applicants are encouraged to contact the Principal Supervisor directly to discuss their application/project.

Assistance will be given to those who are applying to international funding schemes. The successful applicant will be expected to provide the funding for tuition fees and living expenses as well as research costs of £3000 per year.

A tuition fee bursary may be available for well qualified and motivated applicants with First class degree.

Details of costs can be found on the University website: View Website

To apply send a CV and cover letter to

References

Herrmann, A., Rice, M., Levy, R., Pizer, B. L., Losty, P. D., Moss, D., & See, V. (2015). Cellular memory of itypoxia elicits neuroblastoma metastasis and enables invasion by non-aggressive neighbouring cells. ONCOGENESIS, 4. doi:10.1038/oncsis.2014.52

Herrmann, A., Moss, D., & Sée, V. (2016). The Chorioallantoic Membrane of the Chick Embryo to Assess Tumor Formation and Metastasis.. In Tumour Angiogenesis AssaysBook (Vol. 1464, pp. 97-105). doi:10.1007/978-1-4939-3999-2_9

Swadi, R., Mather, G., Pizer, B. L., Losty, P. D., See, V., & Moss, D. (2018). Optimising the chick chorioallantoic membrane xenograft model of neuroblastoma for drug delivery. BMC CANCER, 18. doi:10.1186/s12885-017-3978-x

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