Wrong Parasite, Wrong Host? How Plasmodium Falciparum Erythrocyte Membrane Protein 1 Expression And The Host’s Innate Immune Response Combine To Influence The Inflammatory Response To Malaria In Vitro And In Vivo. Implications For Severe Malaria
Funder
National Health and Medical Research Council
Funding Amount
$707,821.00
Summary
One factor that determines whether some children die of malaria is the type of protein that the parasite expresses on the red blood cell, to help it stick in blood vessels. Our new data suggests that some proteins stimulate excessive host immune response, possibly leading to severe malaria. People's immne response to malaria varies too, and we will discover whether severe malaria occurs when a dangerous parasite strain infects a susceptible host causing an excessive immune response, harming the ....One factor that determines whether some children die of malaria is the type of protein that the parasite expresses on the red blood cell, to help it stick in blood vessels. Our new data suggests that some proteins stimulate excessive host immune response, possibly leading to severe malaria. People's immne response to malaria varies too, and we will discover whether severe malaria occurs when a dangerous parasite strain infects a susceptible host causing an excessive immune response, harming the child.Read moreRead less
Proteasome Inhibitors As Reversers Of Resistance To Artemisinin-based Antimalarials
Funder
National Health and Medical Research Council
Funding Amount
$473,534.00
Summary
Current antimalarial control is highly dependent on Artemisinin Combination Therapy (ACTs), which makes recent reports of decreased clinical efficacy of artemisinins extremely concerning. This project will develop proteasome inhibitors to synergise the activity of artemisinins - effectively reversing resistance. We will confirm that the selected compounds have good bioavailability, low cytotoxicity in human cell lines and efficacy in mouse models of malaria.
Investigating The Therapeutic Potential Of FTY720 For Human African Trypanosomiasis
Funder
National Health and Medical Research Council
Funding Amount
$653,736.00
Summary
FTY720, is a drug currently used to treat multiple sclerosis, which we have shown is also be able to kill the parasite responsible for African sleeping sickness, Trypanosomes. We aim to identify the target the drug acts on in the parasite to have its affect. Our objective is to improve the activity further by chemical modification to produce a potent, orally available and well characterised, non-toxic drug suitable for preclinical development.
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.
Drug targets in the relict plastid of malaria parasites. Malaria is a major world health problem and new drugs are needed urgently. Essential genes are potentially excellent targets for anti-malarial drugs. This project will use a novel strategy to identify genes that the parasite cannot exist without. Function and drug potential of these genes will be explored.
New drugs for malaria that target histone deacetylases. There is no vaccine for malaria and current drugs are failing, contributing to millions of malaria-related deaths each year. The aim of this project is to develop new drugs to address this significant global health issue. This project will focus on drugs that act in novel ways to existing malaria drugs by targeting enzymes that are involved in altering gene expression in the parasite. These kinds of enzymes are recognised drug targets in ot ....New drugs for malaria that target histone deacetylases. There is no vaccine for malaria and current drugs are failing, contributing to millions of malaria-related deaths each year. The aim of this project is to develop new drugs to address this significant global health issue. This project will focus on drugs that act in novel ways to existing malaria drugs by targeting enzymes that are involved in altering gene expression in the parasite. These kinds of enzymes are recognised drug targets in other diseases such as cancer. The outcomes of this project will include advances in malaria drug development that build on Australian drug discovery efforts, seeding further funding opportunities from industry and other sources and contributing research training and capacity building in Australia.Read moreRead less
Transcriptional control of antigenic variation in the malaria parasite Plasmodium falciparum. Malaria is a major health concern for the Australian Defence Personnel recently deployed in East Timor, Afghanistan and the Solomon Islands and is endemic in our immediate neighbours Indonesia and Papua New Guinea. Australia is susceptible to malaria and climate change could extend the mosquitos range to large population centres of Northern Australia causing malaria in Australia. This study would clarif ....Transcriptional control of antigenic variation in the malaria parasite Plasmodium falciparum. Malaria is a major health concern for the Australian Defence Personnel recently deployed in East Timor, Afghanistan and the Solomon Islands and is endemic in our immediate neighbours Indonesia and Papua New Guinea. Australia is susceptible to malaria and climate change could extend the mosquitos range to large population centres of Northern Australia causing malaria in Australia. This study would clarify how malaria parasites evade the host's immune response and help to protect Australia by providing drug targets for the control of this invasive disease.Read moreRead less
Drug targets in malaria parasites. Malaria is rampant throughout our Region and hinders the economies of our neighbours reducing regional prosperity and stability. Australian security and aid personnel deployed in the Region contract malaria infections and global warming could bring malaria-carrying mosquitoes south to Sydney. Australia is pre-eminent in malaria research, making lead discoveries in vaccine and drug development. However, we lack crucial resources to study the parasite in the mo ....Drug targets in malaria parasites. Malaria is rampant throughout our Region and hinders the economies of our neighbours reducing regional prosperity and stability. Australian security and aid personnel deployed in the Region contract malaria infections and global warming could bring malaria-carrying mosquitoes south to Sydney. Australia is pre-eminent in malaria research, making lead discoveries in vaccine and drug development. However, we lack crucial resources to study the parasite in the mosquito phase of its life cycle. The Federation Fellowship will create a malaria mosquito facility to redress this crucial gap in our capability. The Fellowship will double as foreign aid investment by enhancing our capacity to protect ourselves as well as supporting our neighbours.Read moreRead less
Functional proteomics of Giardia. This project will use the latest tools for dissecting and comparing genes and their protein products from one of the most common parasites infecting people, their pets, livestock and wildlife. This protozoan parasite Giardia is also of evolutionary and biological significance in terms of understanding the origin of higher animals from bacteria as well as fundamental questions about the parasitic way of life. Giardia proteins will be identified and characterised ....Functional proteomics of Giardia. This project will use the latest tools for dissecting and comparing genes and their protein products from one of the most common parasites infecting people, their pets, livestock and wildlife. This protozoan parasite Giardia is also of evolutionary and biological significance in terms of understanding the origin of higher animals from bacteria as well as fundamental questions about the parasitic way of life. Giardia proteins will be identified and characterised on the basis of their value in understanding disease processes and treatment, and by working with appropriate industry partners, proteins of commercial value will be exploited.Read moreRead less
Signalling pathways for sexual differentiation of apicomplexan parasites. This project aims to study the sexual development of apicomplexan parasites, which cause major diseases in humans, livestock and wildlife, including malaria. Only sexually differentiated cells can survive in the mosquito vector and hence this development is essential for the parasite's life-cycle. This project will employ a new approach that separates female from male parasites, thus enabling new information to be gleaned ....Signalling pathways for sexual differentiation of apicomplexan parasites. This project aims to study the sexual development of apicomplexan parasites, which cause major diseases in humans, livestock and wildlife, including malaria. Only sexually differentiated cells can survive in the mosquito vector and hence this development is essential for the parasite's life-cycle. This project will employ a new approach that separates female from male parasites, thus enabling new information to be gleaned about the development of these parasites. The expected outcomes are an understanding of the mechanisms of sexual differentiation and a functional characterisation of novel sex-specific molecules. This will provide significant benefits, such as pivotal prerequisites for new approaches to parasite intervention.Read moreRead less