PhD Studentships at University of Nottingham, UK

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Establishment of a pre-clinical screening programme to determine therapeutic efficacy of TCM-based compounds in both a malignant and chemo-prophylactic setting

Department of Division of Pre-Clinical Oncology

Deadline: 31 March

Specific Background

Traditional Chinese medicines (TCM) have shown long-established clinical benefit and this studentship is aimed at examining their role in an oncology setting.

Through collaboration with the Shanghai Research Centre for modernisation of TCM, access will be gained to well-characterised/purified active components extracted from herbs known to exert clinical benefit in cancer patients.

The aim of this project is to establish a chemoprophylactic screen allowing prediction of the efficacy of these active molecules alone and in combination in a clinical setting.

Predictive pre-clinical tumour modelling is essential for effective clinical drug development.

A refined approach will be by using reporter genes to give a read-out of cellular characteristics in real-time both in vitro and in vivo.

To establish in vitro and in vivo screens for TCM which are validated against established chemoprophylactic and chemotherapeutic agents.

Research Methodology:

Cell lines: Will include a panel of different types, representative of each tumour type in terms of mutational profile, as well as pre-malignant lines.

  • Phase I (all compounds): Establish compound potency in relation to positive control agents using proliferation and mitochondrial-based screens.

  • Phase II (compounds associated with potency): Systematic combination of agents showing sub-mM potency.

  • Phase III (lead compounds): Determination of mechanism of action which will include apoptosis assays, transcription factor reporter and kinase assays to identify blockade of signalling cascades, expression of angiogenic factors and modulation of hypoxia-associated factors such as HIF1alpha.

    The project would be suitable for an undergraduate with experience in biomolecular sciences.

    Experience in molecular biology, tissue culture and in vitro assays would be desirable, along with an interest in traditional Chinese medicine.

    In addition, theoretical knowledge of reporter and kinase-based assays would be useful.

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