The role of exosome-like vesicles in host-parasite interactions

BACKGROUND:

Parasitic nematodes are estimated to infect more than 1.5 billion people globally, causing a substantial disease burden. Understanding how these parasites infect their host is an important step towards developing novel ways of controlling and treating nematode infections. Our research seeks to understand the molecular and genetic basis of nematode parasitism, including how the parasite interacts with the host at a molecular level. Parasitic nematodes secrete molecules into their host to manipulate the host environment for their own benefit. Recently, it has been discovered that nematodes package proteins and small RNAs into exosome-like vesicles (ELVs) which they secrete into their host. These molecules can directly target components of the host immune response including host genes and proteins.

We have identified ELVs secreted by the parasitic life cycle stage of Strongyloides nematodes, a gastrointestinal parasite of humans and other animals. The Strongyloides ELVs contain a cocktail of proteases which have a putative role in parasitism. We hypothesise that these proteases manipulate host molecules and immune cells important in the anti-nematode immune response. We are currently expanding this work to also look at the role of small RNAs (e.g. microRNAs) secreted in these ELVs, that could potentially target and regulate the expression of host genes.

PROJECT:

The project aims to address key questions important to understanding the role of ELVs in host-parasite biology, including

• Are ELVs secreted at different stages throughout the infection process?
• Do the contents of the ELVs (proteins and small RNA) change at different stages in infection?
• What components of the host immune response, host cells, or host gene expression do these ELVs target and manipulate?

The PhD project will involve (i) collecting the secreted ELVs from Strongyloides nematodes at different infective life cycle stages and characterising the ELV contents including proteins (using mass spectrometry) and small RNAs (using RNAseq), and (ii) determining the host immune response or other aspects of the host biology that secreted ELVs target and manipulate. You will receive state-of-the-art training in lab-based techniques including transcriptomics, proteomics, small RNA biology, analysis of cell lines exposed to Strongyloides-derived ELVs, immunobiology and co-immunoprecipitation assays.

SUPERVISOR AND LAB:

The successful candidate will join the group of Dr Vicky Hunt - please see our lab website for an overview of the research we do on Strongyloides and other nematodes: www.vickyhuntlab.org

The project will be carried out in collaboration with international experts on nematode genetics and exosome-like vesicles - Dr. Taisei Kikuchi and Dr. Kazunori Murase (University of Miyazaki, Japan), and there will be potential opportunities for visiting these labs in Japan.

CANDIDATE:

We are seeking candidates with a strong interest in infection biology, particularly host-parasite interactions, and an eagerness to understand the molecular basis of parasitism. Candidates should have, or be about to obtain, a First or Upper Second Class UK Honours degree in a relevant field of biological sciences. Experience working in a molecular biology, immunobiology or infection biology lab is preferred, but not essential.

APPLICATIONS:

Informal enquiries are welcomed and should be directed to Dr Vicky Hunt, [Email Address Removed]

Formal applications should be made via the University of Bath’s online application form:
https://samis.bath.ac.uk/urd/sits.urd/run/siw_ipp_lgn.login?process=siw_ipp_app&code1=RDUBB-FP02&code2=0013

Please ensure that you quote the supervisor’s name and project title in the ‘Your research interests’ section.

More information about applying for a PhD at Bath may be found here:
http://www.bath.ac.uk/guides/how-to-apply-for-doctoral-study/

Anticipated start date: 30 September 2019.