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Identifying biomarkers of treatment response in gestational trophoblastic disease through quantitative proteomics analysis of patient samples

About This PhD Project

Project Description

Gestational trophoblastic disease (GTD) is a spectrum of disorders including the pre-malignant hydatidiform mole (HM) through to malignant choriocarcinoma. Methotrexate (MTX)-based mono-chemotherapy, a low toxicity regimen, cures the vast majority of cases. A multi-parametric scoring system (FIGO) is used to predict patients with MTX resistance that require various more toxic combination therapies. However, this system misclassifies ≈30% of patients with innate MTX resistance, unnecessarily delaying commencement of combination agent chemotherapy. Whilst nearly all patients are ultimately cured, some still die from metastatic/multi-drug-resistant disease. We think these deaths can be eliminated by better stratification of patients and/or through development of novel therapeutic strategies. The student, following training in mass-spectrometry-based proteomics and bioinformatics at our commercial partner, Gemini Biosciences, will perform comparative quantitative proteomics analysis of MTX sensitive vs resistant vs multidrug resistant patient tissue samples to identify new stratification biomarkers and novel therapeutic targets. These will be validated using our unique large GTD patient tissue collection with associated clinical data. Possible therapeutic targets will be further tested in our pre-clinical models of GTD using a broad range of cell and molecular biology techniques in vitro and in vivo. In summary, this PhD provides an outstanding opportunity for multidisciplinary training in a diverse research environment, generating data that should change clinical practice and benefit GTD patient outcomes.

This studentship is part of fully funded Enterprise DTP PhD Studentships to start in October 2019, with a stipend of £18,000 p/a. As part of this support, funding is provided at the end of three years for a 6 month writing up period. The studentship is tied to a specific Collaborative Award in Science and Engineering (CASE) project. The student will benefit from additional training through the CASE commercial partner, Gemini Biosciences, in specific areas such as quantitative proteomics and associated bio-informatics data analysis.

Applicants should have prior wet-lab experience in cell and molecular biology or biochemistry. Experience in proteomics or bio-informatics is not required but would be advantageous.

Applicants must ensure they meet all Imperial PhD entry requirements. All students will belong to the Graduate School, which provides a comprehensive Transferable Skills Programme. Consistently rated amongst the world’s best universities, Imperial College London is a science-based institution with a reputation for excellence in teaching and research, valuing diversity and commitment to equality of opportunity.

Please, email your CV (indicating final grades for undergraduate/postgraduate studies) and 1-page motivation letter to Dr Olivier Pardo () before 25/07/19.

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