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FindA University Ltd Featured PhD Programmes

The role of extracellular small RNAs in parasitic nematode infection


Project Description

There is increasing recognition that a variety of cell types from many different organisms secrete RNA into the extracellular space (Sarkies & Miska, 2014). Secreted RNAs are typically encapsulated within membrane-bound vesicles known as exosomes, which protects them from degradation by nucleases in the extracellular environment. Amongst the most abundant RNA species are microRNAs, raising the possibility that extracellular RNA could be a means to transmit gene regulatory information between cells. The mechanism whereby miRNAs become encapsulated into exosomes for secretion, including which RNA-binding proteins are responsible, is unknown. Moreover, there is no clear evidence demonstrating a functional relevance for extracellular RNA in cell-to-cell communication (Sarkies & Miska, 2014).

Recently, parasitic nematodes have been shown to secrete miRNAs in exosomes whilst infecting host organisms (Buck et al., 2014). miRNAs might be secreted by parasites in order to hijack endogenous gene regulatory pathways in the host, but it is not yet clear whether sufficient concentrations of miRNAs within exosomes could be delivered to host cells (Coakley, Buck, & Maizels, 2016). The parasitic nematode Trichinella spiralis, which infects a range of mammalian hosts including humans, is an excellent model to study the function of extracellular miRNAs. T. spiralis possesses both an intracellular and an extracellular stage in their life cycle. T. spiralis larvae infect skeletal muscle and, remarkably, cause terminally differentiated cells to re-enter the cell cycle. The mechanism by which T. spiralis brings about this change is completely unknown.

In this PhD studentship, the student will investigate whether RNAs secreted by T. spiralis might contribute to its pathogenic mechanism. The project will involve close collaboration between the Sarkies laboratory (Faculty of Medicine; MRC Laboratory of Medical Sciences) who have expertise in RNA biology and epigenetics, and the Selkirk laboratory (Faculty of Natural Sciences) who specialise in the molecular biology of parasitic nematode infection. The studentship will involve both experimental and computational analyses of small RNAs in material secreted by T. spiralis. In particular, we will investigate the exact mechanism of secretion employed by the parasite when within muscle cells by characterising an RNA-binding protein that we have discovered in the secreted material. We will also determine the dynamics of miRNA secretion in vivo and investigate their potential role in remodeling of skeletal muscle cells. Together this project will give exciting new insights into the biology of parasitic nematode infection, and characterise an important new paradigm in the study of the role of RNA in host-parasite communication.

To Apply: Please visit our website where an application form can be downloaded. We will only consider candidates who have submitted a full application form by the deadline date.

Funding Notes

This project is ICCS directly funded for UK/EU students only.

If successful the student would receive full tuition fee payment for 3.5 years as well as a tax free stipend amounting to £21,000pa paid in monthly instalments for the duration of their studentship.

References

Buck, A. H., Coakley, G., Simbari, F., McSorley, H. J., Quintana, J. F., Le Bihan, T., … Maizels, R. M. (2014). Exosomes secreted by nematode parasites transfer small RNAs to mammalian cells and modulate innate immunity. Nature Communications, 5(1), 5488. https://doi.org/10.1038/ncomms6488

Coakley, G., Buck, A. H., & Maizels, R. M. (2016). Host parasite communications—Messages from helminths for the immune system: Parasite communication and cell-cell interactions. Molecular and Biochemical Parasitology. https://doi.org/10.1016/j.molbiopara.2016.06.003

Sarkies, P., & Miska, E. A. (2014). Small RNAs break out: The molecular cell biology of mobile small RNAs. Nature Reviews Molecular Cell Biology. https://doi.org/10.1038/nrm3840



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