New Antimalarial Drug Leads Targeting Multiple Species And Life Cycle Stages
Funder
National Health and Medical Research Council
Funding Amount
$818,477.00
Summary
Malaria causes ~200 million clinical cases and >430,000 deaths annually. Prevention and treatment relies on drugs, however malaria parasite drug resistance is an enormous problem. To address this issue, and aim towards eliminating malaria, we need to develop new drugs. This project addresses this important health need by investigating the ability of new chemical compounds, developed at CSIRO, to kill human-infecting malaria parasites during different parts of their complicated lifecycles.
In 2013 there were ~200 million clinical cases of malaria, causing ~600,000 deaths. All antimalarial drugs are now associated with malaria parasite resistance. Thus, new therapies are urgently needed, including new drugs to prevent this disease. We have made the exciting discovery that an existing antimalarial drug can kill malaria parasites in a unique, previously unknown, manner. Here, we will investigate how this occurs and develop new drug candidates for malaria prevention.
The Control And Regulatory Mechanisms Of Artemisinin Induced Dormancy In P. Falciparum
Funder
National Health and Medical Research Council
Funding Amount
$495,552.00
Summary
Malaria is a major global health problem and can only be reliably treated with artemisinin combinations in many areas due to widespread of drug resistance. However a proportion of parasites appear to be able to avoid the lethal effects of the drug by becoming “dormant” following exposure. They resume growth after the drug is wanned, a feature which is reminisent to cell cycle arrest. This study investigates the role of cell cycle machinery in dormancy following arteminsinin treatment.
The Role Of Novel And Essential Bromodomain Proteins In Coordinating Malaria Parasite Gene Regulation And Their Potential As Anti-malarial Targets
Funder
National Health and Medical Research Council
Funding Amount
$689,034.00
Summary
Malaria kills over 400,000 people a year and new therapies are needed. Malaria parasites activate groups of genes by novel mechanisms that could be targeted by drugs. We will characterise a novel group of proteins to identify those that activate genes essential for parasite survival. We will also search for molecules that inhibit the proteins and kill malaria parasites. Thus we will discover how parasites control their genes and identify drug targets and inhibitors for drug development.
Functional Dissection Of Invasion Motor Regulation In Toxoplasma Gondii
Funder
National Health and Medical Research Council
Funding Amount
$500,396.00
Summary
The single-celled intracellular parasite Toxoplasma gondii is the cause of Toxoplasmosis and can be the basis of illness in immunocompromised individuals, eye disease and congenital birth defects. After host cell recognition Toxoplasma needs to activate the invasion machinery to establish a successful infection. We will reveal, at the molecular level, how Toxoplasma achieves this and then screen for drugs that inhibit this process. Compounds identified in this project could act as lead compounds ....The single-celled intracellular parasite Toxoplasma gondii is the cause of Toxoplasmosis and can be the basis of illness in immunocompromised individuals, eye disease and congenital birth defects. After host cell recognition Toxoplasma needs to activate the invasion machinery to establish a successful infection. We will reveal, at the molecular level, how Toxoplasma achieves this and then screen for drugs that inhibit this process. Compounds identified in this project could act as lead compounds to develop new treatments for Toxoplasmosis.Read moreRead less
A Study Of Artemisinin Combination Therapy Given At Delivery To Prevent Postpartum Malaria And To Young Infants To Treat Uncomplicated Malaria
Funder
National Health and Medical Research Council
Funding Amount
$788,850.00
Summary
The proposed studies will investigate the preventive value of a course of combination antimalarial treatment at delivery in pregnant women in malarial areas. The transfer of this treatment into breast milk and to the suckling infant will be investigated since this may protect the infant against malaria but also cause drug-related side-effects. These data will be used, with a study of combination treatment in infants with malaria, to optimise dose regimens in this vulnerable group.
Novel Serological Tools To Aid Malaria Elimination In The Asia-Pacific
Funder
National Health and Medical Research Council
Funding Amount
$1,362,749.00
Summary
In 2014 Asia-Pacific leaders pledged a malaria free Asia-Pacific by 2030. We will contribute to this goal by developing novel antibody detection tests that can identify people with current and recent past infections. We will then evaluate the utility of these tests both in mass screening and treatment programs and for the rapid delineation of areas where transmission persists from those where it has been eliminated. This will address two major roadblocks to malaria elimination in our region.
The Astrocyte: A Crossroads In Cerebral Malaria Pathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$597,598.00
Summary
Malaria is an infectious disease that kills over 1 million people each year. It is prevalent in the Australian region, e.g. PNG and SE Asia. One of its most serious complications is cerebral malaria (CM), which affects the brain and is often fatal. This project will determine whether a very important cell in the brain, the astrocyte, is involved in the disease processes that lead to CM. This is highly relevant to the development of therapies that can be given along with anti-malarial drugs.
Development, Regulation And Role Of Innate Immunological Memory In Malaria
Funder
National Health and Medical Research Council
Funding Amount
$563,860.00
Summary
Innate immunity is traditionally considered to be a short-lived, non-specific first line of defense against pathogens. However, recent reports suggest that innate immune cells can learn from previous pathogen encounters, resulting in enhanced responses on repeat infections with the same pathogen. We will study the role and regulation of innate immunological memory during malaria infection. This will advance our understanding of malaria immunology and will likely aid in the development of vaccine ....Innate immunity is traditionally considered to be a short-lived, non-specific first line of defense against pathogens. However, recent reports suggest that innate immune cells can learn from previous pathogen encounters, resulting in enhanced responses on repeat infections with the same pathogen. We will study the role and regulation of innate immunological memory during malaria infection. This will advance our understanding of malaria immunology and will likely aid in the development of vaccines.Read moreRead less
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.