Project R-15237

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 proteins that could affect the immune system and counteract blood clotting and platelet aggregation. These proteins are therefore very interesting for unraveling (patho)physiological molecular mechanisms. The tick protein Salp15 modulates the immune system by binding to the CD4 receptor on T helper cells and exhibits an immunosuppressive function. However, little is known about its function on human T cells. With this project we want to elucidate the structure of Salp15 and to investigate whether Salp15 has therapeutic potential in (auto)immune diseases. The mechanism of action and the effects of Salp15 on human CD4+ T cells will be studied by using different approaches. Recombinant Salp15 will be enriched with 13C and 15N for nuclear magnetic resonance and thus structure elucidation of this protein and further protein-protein interactions between Salp15 and the CD4 receptor will be studied. The molecular effects of Salp15 on phenotype and function of human T helper cells will be investigated in detail. Finally, the therapeutic potential of Salp15 will be assessed by studying its function on T cells of patients with autoimmunity in vitro and in humanized animal models of disease in vivo. Thus, this project will provide novel insights into the structure-activity relationship of Salp15 and will elucidate its therapeutic potential for autoimmunity.

01 November 2024 - 31 October 2028