3.5 Year MRC PhD Programame: Using MS Imaging (MSI) to explore T. cruzi parasite distribution and drug distribution

Treatment of T Cruzi, the causative agent of Chagas disease has proven extremely challenging, in part due to its complex life cycle in mammalian hosts. There is growing evidence that the parasite resides in difficult to access, immune privileged sites such as ovaries, testis and brain in both acute and chronic disease. Furthermore, the parasites are consistently detected in lymph nodes in chronic disease adding further challenge to developing the right properties in a chemotype to deliver the distributional requirements necessary for sterile cure. Exploring and understanding whether lymph acts a reservoir or just a transient pool for parasites will be critical to this end. Consequently, the ability to better detect both parasites and drug in difficult to access tissue and different tissue regions following treatment in mouse models of infection would add significant value in our understanding of this disease and the drug distributional requirements necessary for treating this disease.
Advances in Mass Spectrometry Imaging (MSI) technology now allows for sub-cellular resolution with SIMS, and MALDI or DESI, with a suitable high resolution MS, are often utilised for drug concentration measurements in tissue (1). Furthermore, although the spatial resolution in MALDI is not sufficient for detection of the parasite it may be possible to use a lipid signature to determine whether parasite is present and combine this with ability to determine drug concentration.
This project will utilise a number of MS approaches on a range of tool compounds to help better understand parasite and drug distribution and consequently the properties needed for a small molecule treatment for Chagas disease.

The University of Dundee is delighted to be recruiting for five PhD studentships, funded for 3.5 years, to start in September 2017. These projects bring together leading experts from the School of Life Sciences (SLS), the School of Medicine (SoM) and the School of Science and Engineering (SSE) to train the next generation of scientists at the forefront of international science. The outstanding biomedical research at the University of Dundee was recognised by its high rankings in REF 2014, with Dundee rated as the top University for Biological Sciences in the UK.

Eligibility: Applications for these MRC studentships are invited from excellent UK* students expected to hold (or be about to achieve) at least a 2:1 Honours degree in a relevant subject.
*Some EU students may be eligible for a full award if you meet Research Council residency criteria and other exceptions may apply.

















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