Investigating helminth-host protein-protein interactions to identify novel immunomodulatory factors

• Funding – self-funded/externally sponsored applicants   (PhD Fees can be found here)
• Applications are accepted year round
• Standard Entry dates – January and September
• Applicants are expected to have a degree (equivalent of Honours or Masters) in a relevant discipline.

Parasitic helminths (worms) can modulate the host immune response, to prevent the immune system from ejecting them. Our previous work has identified several families of proteins from an intestinal nematode: these proteins bind with high affinity to proteins of the immune system, either blocking the activity of the immune system, or changing the response induced. There are multiple effects of parasites on the immune system which have never been fully characterised. In this project we propose a new technique to screen for novel parasite-host interactions.  

 We will first collect the secretions of the murine intestinal nematode Heligmosomoides polygyrus bakeri. These secretions (termed “HES”) contain several known immunomodulatory proteins, including HpARI (binds IL-33 (Osbourn, 2017, Immunity)), HpBARI (binds ST2 (Vacca, 2020, eLife)) and HpTGM (binds TGFBR2 (Johnston, 2017, Nat Commun)).  

 We propose that by taking the total secretions of the parasite and mixing these with host cell homogenates, we can identify known and novel immunomodulatory binders. Through the use of gel filtration fractionation and mass spectrometry, we can estimate the molecular weight of each protein or complex in a mixture: if a parasite and host protein complex together they would increase in size on a gel filtration column. We will therefore begin by showing we can detect these size changes by mixing known immunomodulatory proteins with their known targets: HpARI with IL-33, HpBARI with ST2 and HpTGM with TGFBR2. We will then move onto using more complex mixtures of host cell lysates. If successful, this technique would allow us to use the secretions of less well understood parasites (e.g. human hookworms) to identify how these interact with their hosts.  

This project would therefore use protein characterisation (gel filtration, western blot, ELISA), and proteomic techniques (mass spectrometry), as well as bioinformatic analysis of large proteomic datasets to identify new parasite-host interactions.  

These parasite immunomodulatory proteins could have multiple future uses: they may make good vaccine candidates against parasitic infections, or the immunomodulatory proteins could be used as treatments for immune-mediated diseases.  

Our research community thrives on the diversity of students and staff which helps to make the University of Dundee a UK university of choice for postgraduate research.  We welcome applications from all talented individuals and are committed to widening access to those who have the ability and potential to benefit from higher education.