Helminth Secretomes: From Vaccines To Novel Anti-inflammatory Biologics
Funder
National Health and Medical Research Council
Funding Amount
$938,910.00
Summary
Billions of people in developing countries are infected with parasitic worms, but they have been eradicated from industrialised nations. Humans co-evolved with worms, so their recent removal has deprived us of signals required to keep inflammation in check. My research focuses on worm molecules that can be used to (1) develop vaccines to combat these parasitic infections in developing countries, and (2) as a novel platform of anti-inflammatory therapeutics for use in industrialised nations.
Antibodies That Inhibit Erythrocyte Invasion By Plasmodium Falciparum And Their Role In Protective Immunity
Funder
National Health and Medical Research Council
Funding Amount
$389,250.00
Summary
Malaria continues to be a leading cause of death and disease globally, resulting in up to 3 million deaths annually, mainly among children. After repeated episodes of malaria, children that survive develop immune responses that protect them against further episodes. Currently, it is not well understood how these protective immune responses work. Malaria parasites infect red blood cells and multiply inside them, leading to the symptoms and serious complications of malaria. Antibodies that block t ....Malaria continues to be a leading cause of death and disease globally, resulting in up to 3 million deaths annually, mainly among children. After repeated episodes of malaria, children that survive develop immune responses that protect them against further episodes. Currently, it is not well understood how these protective immune responses work. Malaria parasites infect red blood cells and multiply inside them, leading to the symptoms and serious complications of malaria. Antibodies that block the entry of parasites into red blood cells have been found in adults who are immune to malaria, and can be stimulated by certain vaccines, but little is known about this immune response and whether it is effective in protecting against malaria. Many investigators have focussed on the detection of antibodies, but we will focus on the function of antibodies in blocking parasite entry into red blood cells, thereby blocking parasite growth. We will examine how these antibodies develop among children at risk of malaria living in a region of Kenya where malaria is a major cause of death, and whether these antibodies protect children against malarial illness. Malaria parasites produce a variety of different proteins that enable them to stick and then enter red blood cells. We will identify the main proteins that antibodies target to block malaria growth. We will also determine whether variations in the proteins produced by malaria are used to avoid immune responses. Results from these studies will advance our understanding of how the immune system protects against malaria. With this knowledge, vaccines can be designed that will target essential malaria proteins, and reduce or prevent malaria infection and illness.Read moreRead less
Genomic-based Tools To Support The Control Of Urogenital Schistosomiasis And Hepatic Opisthorchiasis
Funder
National Health and Medical Research Council
Funding Amount
$419,180.00
Summary
Over 100 million people are affected by parasitic flukes that promote malignant tumours. Parasite control depends on a single drug, making resistance an imminent threat. I will deliver new genomic tools to unravel the complex interactions between parasites and humans, and explore parasite population diversity on a continental scale. I will then prioritise a panel of anti-parasitic drug targets and vaccine candidates to deliver the next generation of interventions against parasitic diseases.
Secreted Exosome-like Vesicles From The Carcinogenic Liver Fluke
Funder
National Health and Medical Research Council
Funding Amount
$771,543.00
Summary
Parasitic liver flukes secrete microscopic cell-like vesicles into the bile ducts when feeding on infected humans. These vesicles, called exosomes, are taken up by the cells lining the bile ducts and promote them to become pre-cancerous. We will characterise the contents of these fluke exosomes and identify the key molecules on their surfaces that can be used to prevent exosome uptake by cells and ultimately form the basis of a vaccine that prevents fluke infection and subsequent liver cancer.
Targeting Schistosome Calcium Signalling To Improve And Broaden Praziquantel Efficacy
Funder
National Health and Medical Research Council
Funding Amount
$481,661.00
Summary
Schistosomiasis is caused by parasitic worms, treatment relies solely on praziquantel (PZQ). Schistosomes respond and recover from PZQ exposure through modulation of the gene CamKII. We will target this gene to both increase and extend the efficacy of PZQ in both adult parasites and in refractory juvenile parasites. Research will expand into assaying CamKII inhibitors to maximise effectiveness and take this work into animal models of this disease.
Tropical Diseases: Translating Discoveries Into Better Health
Funder
National Health and Medical Research Council
Funding Amount
$19,803,660.00
Summary
Major progress being made in control of many infectious diseases occurring in tropical areas, including malaria worms and the bacteria that causes strep throat. However, currently available tools will not permit their full control or elimination. This program is aimed to improve understanding of these diseases and to develop the much needed tools that will be required for their elimination.
Understanding How A Parasite-derived Peptide Prevents Immune Mediated Demyelination
Funder
National Health and Medical Research Council
Funding Amount
$496,978.00
Summary
Over millennia of co-evolution with humans, parasitic worms have developed the capacity to modulate the human immune system. We have characterised and identified novel molecules secreted by these worms. In this project we will assess the therapeutic potential of the parasite molecules using animal models of relapsing remitting multiple sclerosis.
Cytoskeletal Remodeling Of The Erythrocyte During Malaria Parasite Invasion
Funder
National Health and Medical Research Council
Funding Amount
$559,807.00
Summary
Malaria parasites cause profound human disease through infection of the red blood cell. How parasites break into the red cell is incompletely understood. Foremost, the parasite must induce radical changes in its structural integrity to enter, but to date no study has been able to precisely map these cellular events. In this research program we aim to dissect the entire process using state-of-the-art imaging, molecular biology and proteomics to shine new light on this key step in malaria disease ....Malaria parasites cause profound human disease through infection of the red blood cell. How parasites break into the red cell is incompletely understood. Foremost, the parasite must induce radical changes in its structural integrity to enter, but to date no study has been able to precisely map these cellular events. In this research program we aim to dissect the entire process using state-of-the-art imaging, molecular biology and proteomics to shine new light on this key step in malaria disease establishment.Read moreRead less
A Transmission-Blocking Vaccine To Prevent Toxoplasmosis
Funder
National Health and Medical Research Council
Funding Amount
$850,225.00
Summary
Toxoplasma gondii causes a globally important zoonotic disease. It is transmitted by cats, and finds its way into our food chain via infected meat and contaminated water. We have used a unique functional genomics pipeline to discover proteins crucial for reproduction of Toxoplasma in the cat. We will now test combinations of these proteins to immunise cats and prove that we can develop a vaccine that blocks transmission of this highly significant parasitic disease.
My research team is focused on human parasites of major relevance to the Australian water industry and/or global public health. Our primary focus is the use of advanced technologies to improve understanding of these parasites and to utilize this information to underpin development of new drugs to treat them and novel diagnostic tests to improve their control.