TGF-beta is a mammalian cytokine which has a large range of effects on different cells in the body: it is involved in development, immunosuppression, cancer progression and fibrosis, amongst many other pathways. The parasitic nematode Heligmosomoides polygyrus secretes a family of TGF-beta mimics (TGMs) which bind to the TGF-beta receptor (Johnston, 2017, Nat Commun). There are 10 TGMs in the parasite’s genome (Smyth, 2018, Int J Parasitol), some of which have been characterised to agonise the host TGF-beta receptor on immune cells (causing immunosuppression) while others block the host TGF-beta receptor on stromal cells (suppressing fibrosis). Several of the TGMs have not been characterised, and their roles in vivo are not well understood. Additionally to binding the host TGF-beta receptor, the TGMs also bind to co-receptors on host cells (Singh, 2023 Biorxiv), allowing them to target their activity to specific host cells in vivo, something which mammalian TGF-beta cannot do. If we can better understand how the parasite targets the TGF-beta pathway on specific host cells, we could develop new treatments for immune-mediated or fibrotic diseases.

In this project, the PhD candidate will treat immune and stromal cells with different TGM proteins, as well as mutants, chimeras and fusions of these proteins, to determine the activity of these proteins on host responses. We will focus on the signalling downstream of the TGF-beta receptor and the co-receptors that the TGMs ligate, including CD44 and CD49d (van Dinther, 2023, PNAS; Singh, 2023, Biorxiv). We will use a range of biochemical and immunological techniques to determine how the TGMs affect signalling in immune cells including mast cells, innate lymphoid cells and fibroblasts.

Students will be trained in tissue culture, immune cell purification, biochemical signalling assays, flow cytometry and mammalian cell protein expression.

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.

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