Modulation Of Leishmaniasis By The Proinflammatory Cytokines TNF
Funder
National Health and Medical Research Council
Funding Amount
$288,911.00
Summary
We have established a mouse model that has been genetically modified and cannot produce the cytokine tumour necrosis factor. This cytokine is secreted in the beginning of the inflammatory response. If these mice are infected with a parasite they are not able to heal the infection and die quickly. We can demonstrate that these mice cannot regulate the beginning inflammatory response and do not form a cellular infiltrate at the site of infection.
Identification Of Novel Strategies To Mediate Immunity Against Intracellular Pathogens
Funder
National Health and Medical Research Council
Funding Amount
$325,084.00
Summary
The immune system consists of two arms - innate and adaptive. Current vaccine strategies rely mainly on adaptive features of the immune system to mediate immunity against pathogens. Many pathogens have evolved sophisticated strategies to manipulate the adaptive immune system to render it ineffective. This project will investigate microbial detection by the innate immune system, and aims to discover novel, more effective strategies to mediate immunity against intracellular pathogens.
Enhancing Host Defence Against Intracellular Pathogens By Preventing INOS Interaction With A Negative Regulator, SSB-2
Funder
National Health and Medical Research Council
Funding Amount
$448,881.00
Summary
Secretion of nitric oxide (NO) gas by immune cells is a critical defence mechanism for the killing of intracellular pathogens. Production of NO within cells is regulated by the enzyme iNOS. We propose that preventing iNOS from interacting with its natural inhibitor protein (SSB-2) would allow enhanced and prolonged iNOS expression leading to increased NO and increased killing of pathogens such as the mycobacterium tuberculosis and the Leishmania parasite.
Fetal Immune Response To Vertical Transmission Of Toxoplasma Gondii
Funder
National Health and Medical Research Council
Funding Amount
$320,891.00
Summary
Toxoplasma gondii is a parasite that is a leading cause of human abortion and congenital infections of newborns. In addition, recent research implicates Toxoplasma in diagnoses of schizophrenia and other neuromental conditions. Study of Toxoplasma, it's transmission and effects of infection and development of tools such as vaccines and diagnostic technologies will lead to an improvement in health of mothers, newborns and the wider population.
Targeting Toxoplasma Gondii Latent Stages Responsible For Chronic Disease
Funder
National Health and Medical Research Council
Funding Amount
$697,107.00
Summary
Many microbial pathogens become resistant to host immune response and drugs by entering a slow-growing, dormant state. These stages are commonly responsible for long term, chronic infections. We will investigate the molecular basis of dormancy in Toxoplasma gondii, which infects one in three people. These studies will identify metabolic pathways that are essential for dormancy with the view of developing new therapies for treating long term, recurrent infections.
Polysaccharide Biosynthesis As A New Drug Target In Leishmania Parasites
Funder
National Health and Medical Research Council
Funding Amount
$422,517.00
Summary
Leishmania are protozoan parasites that cause a number of important diseases in humans, afflicting more than 12 million people worldwide. There are currently few drugs that target infectious disease causing stages of these parasites. We have recently shown that Leishmania parasites accumulate a highly unusual sugar polymer when they infect mammalian cells, which appears to be important for infectivity. In this proposal , we will investigate how this sugar polymer is made, identify enzymes involv ....Leishmania are protozoan parasites that cause a number of important diseases in humans, afflicting more than 12 million people worldwide. There are currently few drugs that target infectious disease causing stages of these parasites. We have recently shown that Leishmania parasites accumulate a highly unusual sugar polymer when they infect mammalian cells, which appears to be important for infectivity. In this proposal , we will investigate how this sugar polymer is made, identify enzymes involved in its synthesis and develop new chemical tools for generating highly specific inhibitors of Leishmania sugar biosynthesis. This project will provide new insights into processes that are essential for the survival and infectivity of an improtant group of human pathogens, and lead to the development of new classes of enzyme inhibitors with anti-parasite activity.Read moreRead less
Small Molecule Therapeutics: From Infectious And Parasitic Diseases To Cancers
Funder
National Health and Medical Research Council
Funding Amount
$763,845.00
Summary
I will lead a team of medicinal chemists to discover better treatments of diseases focused in two major domains. On one hand, I will discover new drugs to treat certain parasitic diseases such as Sleeping Sickness, Chagas disease and malaria, all caused by protozoal parasites. On the other hand, I will discover new drugs to treat certain cancers, in particular acute myeloid leukemia and Burkitt’s lymphoma, caused by dysfunction of certain types of enzymes called histone acetyltransferases.