Professor Lewis will pursue 4 research projects over the 5 year of the Fellowship. PROJECT 1 will discover and characterise new ion channel blockers from cone snail venom that modulate pain pathways. This project has determined the molecular pharmacology of chi-conopeptides currently in Phase II pain trials and recently patented a new class of omega-conotoxins with a superior efficacy-side effect profile and exciting clinical potential. Project 1 is supported by an NHMRC Program grant (2010-2014) in a collaboration with Prof Alewood, Adams and Christie. PROJECT 2 will characterise the mechanism of GPCR activation using receptor mutants and novel conopeptides to probe extracellular surface conformations linked to the GPCR activation cycle, and is supported by an NHMRC Project grant (2011-2013) in a collaboration with Prof Thomas. PROJECT 3 will discover and characterise spides venom peptides that modulate sodium channels. This project has already identified a number of novel spider venom peptides that target specific sodium channels, and is supported by an ARC Discovery grant (2011-2014) in a collaboration with Prof King and Alewood. PROJECT 4 will dissect the molecular pharmacology of ciguatoxin that underly the diverse sensory disturbances to allow better treatment and detection in a collaboration with Dr Vetter. This Fellowship would leverage (i) well-funded collaborations with top Australian and international scientists and a talented research team supported by a UQ Postdoctoral Fellowship and an NHMRC CDA, and (ii) an outstanding Institute equipped with leading edge technologies for high throughput and high content discovery, and proteomic and transcriptomic analysis. A Fellowship will ensure that this exciting program of research remains at the forefront of international research efforts on toxins, pain pathways and membrane protein structure-function.