Elucidation of platelet activation pathways during invasive mould infections

Currently, over one billion fungal infections occur each year of which over two million develop into life-threatening invasive mycoses. At the same time, our current anti-fungal therapies are ineffective, expensive and show substantial side effects. As a result, invasive fungal infections present with unacceptable mortality rates of up to 95%. This shows the clear need for improved treatment regimes for invasive fungal infections.
Recent research has unravelled new unexpected immunological platelet functions in response to infectious agents. Platelet-bacterial aggregation can release protective antimicrobial factors but also lead to thrombus formation, exaggerated inflammatory responses or thrombocytopenia.
One of the hallmarks of invasive mould infections is the formation of thrombi leading to tissue necrosis and tissue damage. Fungal pathogens readily interact with platelets indicating the potential role of fungal mediated platelet activation in aggravating disease progression. However, next to nothing is known about the molecular basis of the interaction between fungal pathogens and platelets.

Hypothesis: We therefore hypothesise that platelet-fungal interactions during invasive infection leads to platelet activation.
To test this hypothesis, we will:
1.) Analyse the ability of fungal pathogens to induce platelet activation and secretion.
2.) Characterise platelet receptor(s) and downstream signalling pathways involved in fungal recognition.
3.) Characterise platelet interactions in blood samples from predisposed patients.
4.) Investigate the interaction between fungal spores and platelets in a zebrafish larval model.