Project R-12955

Thrilled by ticks to investigate protein Salp15 in (auto)immune disease (Research)

Ticks are an increasing plague for humans and animals due to the pathogens they can transmit. However, tick saliva contains many interesting proteins that, among other things, affect the immune system and counteract blood clotting and platelet aggregation. These proteins are therefore very interesting for unraveling (patho)physiological molecular mechanisms. In addition, proteins from tick saliva can be used for the diagnosis and treatment of various diseases. The tick protein Salp15 modulates the immune system by binding to the CD4 receptor on T helper cells, lymphocytes that play a key role in adaptive immune responses, but are also involved in autoimmune responses. The aim of this project is to elucidate the structure of Salp15 and to investigate whether Salp15 can be used for therapeutic treatment of (auto)immune diseases. To this end, the mechanism of action and the effects of Salp15 on human CD4+ T cells is being studied by using a multidisciplinary approach. At the Department of Biochemistry of Maastricht University, Salp15 will be chemically synthesized using solid-phase peptide synthesis and native chemical ligation techniques, allowing the modification of the protein at one specific site. In addition, Salp15 will be produced by recombinant expression, so that it can be enriched with 13C and 15N for nuclear magnetic resonance and thus structure elucidation of this protein. Furthermore, the protein-protein interactions between Salp15 and the CD4 receptor on T helper cells will be studied. At the Department of Immunology and Infection, BIOMED institute of Hasselt University, the effects of Salp15 on the phenotype and function of T helper cells will be investigated. Human T helper cells will be used for this. Finally, the effect of Salp15 on the function of T cells in patients with an autoimmune disease will be examined in vitro and humanized animal models of disease in vivo. This project will not only provide insight into the structure-activity relationship of the protein Salp15, but it will also demonstrate the therapeutic potential of this protein.

01 October 2022 - 30 September 2026