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Investigating the molecular mechanism of tanshinone 2A in cancer treatment using a tractable model system

  • Full or part time
  • Application Deadline
    Monday, February 10, 2020
  • Competition Funded PhD Project (European/UK Students Only)
    Competition Funded PhD Project (European/UK Students Only)

Project Description

Identifying new therapeutic approaches for cancer treatment remains a societal priority. Validating tradition medicines, such Tanshinone 2A derived from Red Sage, may provide such an approach as it is widely proposed as a potential cancer treatment, yet its molecular mechanisms in cancer treatment remains unclear. Defining this mechanism will help to validate its clinical use. We will employ the tractable model system, Dictyostelium discoideum, to investigate the molecular mechanism of Tanshinone 2A, focusing on mTOR signalling as its therapeutic target. We have shown mTOR signaling is regulated by Tanshinone 2A in Dictyostelium, and have identified key proteins necessary for this effect, providing unique insight to its molecular mechanism. Structure-activity relationship studies have also highlight compounds with potential for increased potency. The project will also involve critical translational aspects through collaboration with Dr Pardo, as a cancer research expert. In addition to providing key knowledge of cancer treatment and relevant animal/human models to validate discoveries, he will also provide cutting-edge research approaches such as mass-spectrometry-based approaches to identify Tanshinone interactor protein from Dictyostelium and mammalian cell lysates.
This project will therefore provide synergistic advances in biomedical and translational research to help improve cancer treatment and ultimately societal health.

This PhD project will be supervised jointly by:
1. Prof Robin SB Williams, Department of Biological Sciences, Royal Holloway University of London
2. Dr Olivier E Pardo, Department of Surgery and Cancer, Imperial College
Applicants are invited to contact supervisor(s) by email ahead of submitting their application. Further information about applying for a postgraduate course at Royal Holloway can be found here:
https://www.royalholloway.ac.uk/studying-here/applying/postgraduate/how-to-apply/

Applications should be submitted online:
https://admissions.royalholloway.ac.uk/#/HEapplicationForm////////1

Funding Notes

Shortlisted eligible studentship applicants, will be notified within two-three weeks of the application deadline. Formal studentship interviews will usually be held within three-four weeks of the application deadline.
The funding for the project will cover home/EU tuition fees and a yearly stipend.

References

Perry et al & Williams (2019) A new mechanism for Cannabidiol in regulating the one-carbon cycle and methionine levels in Dictyostelium and in mammalian epilepsy models, British Journal of Pharmacology, In Press
Schaf, Damstra-Oddy & Williams (2019) Dictyostelium discoideum as a pharmacological model system to study the mechanisms of medicinal drugs and natural products. Int. J. Dev Biol. In Press
Williams & Andrews (2019) Advice on avoiding the Valley of Death: Insights from a 3Rs model of aversive and emetic compound identification. ALTEX, doi:10.14573/altex.1810182, In Press (see here)Warren, Walker, Williams, 2018. All You Need Is Fats-for Seizure Control: Using Amoeba to Advance Epilepsy Research. Front Cell Neurosci. 12, 199.
Cocorocchio et al., 2018. Curcumin and derivatives function through protein phosphatase 2A and presenilin orthologues in Dictyostelium discoideum. Dis Model Mech. 11.
Kelly et al., 2018. Diacylglycerol kinase (DGKA) regulates the effect of the epilepsy and bipolar disorder treatment valproic acid in Dictyostelium discoideum. Dis Model Mech. 11.
Otto, Sharma, Williams, 2016. Non-Catalytic Roles of Presenilin Throughout Evolution. J Alzheimers disease
Chang et al., 2015a. Seizure control by derivatives of medium chain fatty acids associated with the ketogenic diet show novel branching-point structure for enhanced potency. J. Pharmacol. Exp. Ther. 352, 43-52.
Chang et al., 2015b. Seizure control by derivatives of medium chain fatty acids associated with the ketogenic diet show novel branching-point structure for enhanced potency. J Pharmacol Exp Ther. 352, 43-52.
Ludtmann et al., 2014. An ancestral non-proteolytic role for presenilin proteins in multicellular development of the social amoeba Dictyostelium discoideum. J Cell Sci. 127, 1576-84.
Chang Walker, Williams, 2014. Seizure-induced reduction in PIP3 levels contributes to seizure-activity and is rescued by valproic acid. Neurobiol. Dis. 62, 296-306.
Chang et al., 2013. Seizure control by ketogenic diet-associated medium chain fatty acids. Neuropharmacology. 69, 105-114.
Chang et al., 2012. The antiepileptic drug valproic acid and other medium-chain fatty acids acutely reduce phosphoinositide levels independently of inositol in Dictyostelium. Dis. Model. Mech. 5, 115-124.
Williams et al., 2006. Towards a molecular understanding of human diseases using Dictyostelium discoideum. Trends Mol. Med. 12, 415-424.
Williams et al., 2002. A common mechanism of action for three mood-stabilizing drugs. Nature. 417, 292-295.

How good is research at Royal Holloway, University of London in Biological Sciences?

FTE Category A staff submitted: 24.00

Research output data provided by the Research Excellence Framework (REF)

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