Fresh-water snails are hosts of the parasite ©buteo/Shutterstock
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, with naïve snails being preferred. After some time, the next stage – cercariae leave infected snails, and then proceed to infect various mammals . 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.
How do these chemokinetic responses depend on water temperature, an important consequence of the warming climate. We will combine experimental assays, quantitative analyses, and mathematical modelling, to study how motility depends on temperature, in different species.
The current state-of-the-art in studying parasite movement relies on simple, qualitative measures. This project will deliver a new standardised analytical approach to phenotyping larval motility and reveal for the first time the fluid physics of the snail infection process, combining diverse methods including fast live imaging, culturing, microfluidic assays, micromanipulation, timeseries analysis, and modelling.
This is an exciting and novel research direction with many open questions. The student will be involved in the design and scope of this project, tailoring the emphasis to according to their background and expertise.
Candidate requirements
The student must have significant motivation in conducting interdisciplinary research. Prior training in a quantitative discipline and proficiency in bioimaging and wet-lab experiments are highly desirable.
Project partners
This GW4+ partnership is a new collaboration between University of Exeter and the Natural History Museum. The project relies on the world-leading expertise in schistosomiasis related research.
Training
The student will be based at the LSI (Exeter), a major hub for pioneering interdisciplinary research. They will have access to state-of-the-art lab and computational facilities. They will also have the opportunity to conduct a portion of this research at the NHM in London, with access to unique culturing facilities.
Further reading
Bentley et al, Phenotyping single-cell motility in microfluidic confinement, Elife, 11, e76519 (2022)
Poon et al, Ciliary propulsion and metachronal coordination in reef coral larvae, Biorxiv, 2022.09, 19.508546 (2022)
Schistosoma mansoni cercariae swim efficiently by exploiting an elastohydrodynamic coupling, Nature Physics 13 (266-271) (2016)
Ludtmann et al, Protein kinase C signalling during miracidium to mother sporocyst development in the helminth parasite, Int. J. for Protistology 39 1223-1233 (2009).
Museum supervisor
Funded by
