Discovery Early Career Researcher Award - Grant ID: DE230101173
Funder
Australian Research Council
Funding Amount
$374,318.00
Summary
Inhibiting adenylate-forming enzymes via a new reaction-hijacking mechanism. This project aims to identify and validate the adenylate-forming enzymes that are susceptible to reaction-hijacking inhibition in malaria parasites. This class of enzymes can be induced to synthesise their own nucleoside sulfamate inhibitor conjugates via a novel mechanism. This project expects to provide new knowledge about the molecular basis of this novel inhibition mechanism and susceptible target enzymes in the par ....Inhibiting adenylate-forming enzymes via a new reaction-hijacking mechanism. This project aims to identify and validate the adenylate-forming enzymes that are susceptible to reaction-hijacking inhibition in malaria parasites. This class of enzymes can be induced to synthesise their own nucleoside sulfamate inhibitor conjugates via a novel mechanism. This project expects to provide new knowledge about the molecular basis of this novel inhibition mechanism and susceptible target enzymes in the parasites. Adenylate-forming enzymes play critical roles in a diverse range of biochemical pathways, such as protein translation and fatty acid metabolism. The project seeks to deliver a new paradigm for the design of future antiparasitic agents.Read moreRead less
Isolation and analysis of novel caspases. Apoptosis is an evolutionarily conserved cellular process which must be tightly controlled for normal development and to avoid disease. Rapid progress has been made recently in the elucidation of apoptotic pathways, but many important components are likely still unknown. The caspases constitute the effector arm of apoptotic signalling pathways and some members play important roles in cytokine maturation. We aim to identify novel caspases using an innovat ....Isolation and analysis of novel caspases. Apoptosis is an evolutionarily conserved cellular process which must be tightly controlled for normal development and to avoid disease. Rapid progress has been made recently in the elucidation of apoptotic pathways, but many important components are likely still unknown. The caspases constitute the effector arm of apoptotic signalling pathways and some members play important roles in cytokine maturation. We aim to identify novel caspases using an innovative technique, and to characterise their function and regulation. Molecules identified in this project may be candidate targets for therapies which modulate apoptosis for treatment or prevention of disease, or diagnostic reagent development.Read moreRead less
Structural and functional characterisation of compounds that inhibit the malarial aminopeptidases. Malaria is the world's most prevalent parasitic disease. Due to the rapid spread of drug resistant parasites there is a need to develop new antimalarial drugs. In this proposal we will characterise new targets and novel methods of inhibition that will form the basis of a new mechanism for antimalarial drugs.