Platelets play a fundamental role in the maintenance of normal blood, vascular integrity and healing. The ’cell based model of homeostasis’ describes this central role leading to the generation of a thrombin burst that leads to platelet aggregation and coagulation, and ultimately the cessation of blood loss. Under pathological conditions platelets can be activated leading to thrombosis resulting in mycocardial infarction, stroke, deep vein thrombosis and pulmonary embolism. In some cases, platelet activation can lead to small fine clots forming resulting in disseminated intravascular coagulation and multiple organ failure. Novel strategies to treat platelet function at the molecular level has proven challenging.
The toxin, derived from the bacterium Bacillus anthracis, has previously been shown to gain access to the intracellular environment where it can modulate molecular events. We have previously shown utility of this system, using a mimetic delivery platform modelled on Anthrax, to mediate delivery of short interfering RNA and antisense oligonucleotides. It has been previously shown that anthrax toxin can modulate platelet activity by targeting mitogen activated protein kinase (MAPK) activity.
This project will investigate the potential of this system to effect delivery of peptides targeting key molecular pathways of platelet activation in an effort to develop novel anti-platelet therapies. Key research methods include molecular biology assays, bacterial cell culture, recombinant protein production and characterisation, bacterial cell cloning, Western blot immunodetection, platelet aggregometry, confocal microscopy and mammalian cell culture.