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Ex vivo drug screening using human tissue to personalise cancer therapy and replace murine avatars for high-grade brain tumours


Project Description

Supervisor(s): Principle Investigator; Prof Thomas Helleday, Co-investigators Dr. Spencer Collis, Dr. Juha Rantala, Mr. Ola Rominyi and Dr. Greg Wells


Project details:
Glioblastoma (GBM) is the most common and aggressive brain cancer worldwide, treatment options for patients are extremely limited. This studentship aims to investigate potential new therapeutic options for patients by direct observation of cancer-specific phenotypic responses without the use of murine avatars and independently of molecular biomarkers.

Over the last 15 years biomarkers have driven targeted/precision medicine, unfortunately only a sub-population of patients will be treated based on their genetic or protein biomarker profile. Genetic biomarkers for GBM include; IDH mutations and MGMT promoter methylation status. However, these have no impact on the treatment options available for patients due to the lack of potential therapeutic options. One method of investigating efficacious treatment options in GBM is to use patient-derived xenograft models to provide more direct predictions of drug response for an individual patient. However, this is an extremely timely and costly approach.

This PhD studentship aims to approach this unmet need from a different angle. Ex vivo drug response profiling (ex vivo screening) is a method of screening targeted inhibitors and chemotherapies on a tumour biopsy or surgical tissue, directly from the patient. Using a high throughput drug screen (> 150 compounds), multi-parameter high content microscopy at the single cell level, and sophisticated image analysis algorithms it is possible to develop a patient specific pharmacological profile. Ex vivo screening has the potential to identify new, individualised treatment options for patients with GBM in a cost effective and timely manner.

The student will be trained in all aspects of ex vivo screening methodology including sample preparation, dissociation, tissue culture, high throughput drug screens, immunofluorescence staining, advanced high content microscopy and data analysis. The project will be supervised by a highly experienced and successful team with an excellent publication record.

More Information regarding the team can be found here:
https://www.sheffield.ac.uk/oncology-metabolism/staff/helleday
https://www.sheffield.ac.uk/oncology-metabolism/staff/collis

Funding Notes

Funding:
Funded PhD Project UK/EU

Proposed start date: 01/03/2020

Salary/stipend rate: £15,009

References

Entry Requirements:
Candidates must have a first or upper second class honors degree or significant research experience.

Enquiries:
Interested candidates should in the first instance contact: Dr Greg Wells [email protected], or Dr Spencer Collis [email protected]

How to apply:
Please complete a University Postgraduate Research Application form available here: www.shef.ac.uk/postgraduate/research/apply

Please clearly state the prospective main supervisor in the respective box and select Oncology and Metabolism as the department.

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