PhD Studentship: NERC GW4+ DTP Studentship for 2024 Entry - Comparative Analysis and Modelling of Cila Motility in a Major Disease-causing Parasite

The GW4+ DTP consists of the Great Western Four alliance of the University of Bath, University of Bristol, Cardiff University and the University of Exeter plus five Research Organisation partners: British Antarctic Survey, British Geological Survey, Centre for Ecology and Hydrology,  the Natural History Museum and Plymouth Marine Laboratory. The partnership aims to provide a broad training in earth and environmental sciences, designed to train tomorrow’s leaders in earth and environmental science.

For eligible successful applicants, the studentships comprises:

• An stipend for 3.5 years (currently £19,237 p.a. for 2024-25) in line with UK Research and Innovation rates
• Payment of university tuition fee;
• A research budget of £11,000 for an international conference, lab, field and research expenses;
• A training budget of £3,250 for specialist training courses and expenses

Project Background

Schistosomiasis is a major water-borne disease that severely impacts human health, infecting 200 million people, leading to 200,000 deaths/year. This devastating parasitic disease is most prevalent in sub-Saharan Africa, where it is transmitted to humans through cercariae larvae in infected lakes/rivers. The parasite is a flatworm with an unusual life cycle. Once ejected from faeces (of infected mammals), schistosome eggs hatch to produce many motile larvae called miracidia which first infects an intermediate host – freshwater snails. This is a short-lived stage in which the larvae swims using a dense covering of cilia to locate the snail host (Fig.1), with naïve snails being preferred. After some time, the next stage – cercariae leave infected snails, and then proceed to infect various mammals (Fig.2). The entire cycle then begins anew.

Much is known about the parasite’s cell and immunobiology, but little in terms of the physical mechanisms of infection. If we can better characterise and model how infection proceeds in the first instance in snails at a deep quantitative level, particularly the process of selection and migration towards the host, then this will ensure that we can better monitor the virulence of different strains. We will also be able to reveal any species-specific interactions between the intermediate host and parasite, and thus predict how these interactions may be affected by environmental perturbations, such as the warming global climate. This project is a unique opportunity to apply mathematical modelling, fluid dynamics and data analysis to a major environmental and global health challenge that is also rich in novel biology.

Project Aims and Methods

• This highly interdisciplinary project will measure, quantify and model the infection process. We will focus on miracidia (which only infects snails), since effective control over the dispersal of snail chemostimulants and infection of the intermediate host will in turn reduce human infections. Specific aims:
• How do the miracidia larvae swim? Microscale movement is counter-intuitive and dominated by viscosity rather than inertia. We will measure and quantify miracidia motility (propulsion and ciliary dynamics) over its short life cycle using the model schistosome S. mansoni. Larval swimming will be investigated in the presence of snail-derived peptides and proteins.
• What sets snail-parasite specificity? This has been observed anecdotally but not quantified systematically. We will assay and compare motility patterns for distinct parings of snail-parasite species (these are only available from the NHM collection), including using live snail hosts.A training budget of £3,250 for specialist training courses and expenses

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