Host-directed Therapy For Malaria: Host Cell Signalome As A Target
Funder
National Health and Medical Research Council
Funding Amount
$898,043.00
Summary
Malaria parasites kill 450,000 children a year and impact on the economic development of communities. Spreading drug resistant malaria parasites within Australia's South-East Asian neighbours creates an urgent and unmet need for new drug treatments. We will characterise host signals required for parasite survival in immature erythrocytes and identify host-directed, ready to develop, resistance-proofed drugs to kill malaria parasites.
Plasmodium falciparum is the most lethal malaria parasite that infect humans. Our work will reveal how this malaria parasite governs host tropism, fertilization and immune evasion by using the 6-cysteine family of proteins which are abundantly expressed on its surface. This proposal will explore novel ways using the smallest types of antibodies, called nanobodies, to block the function of these proteins and therefore prevent malaria infection.
Structure And Biophysical Analysis Aided Design Of Novel Toxoid Vaccines For A Major Class Of Bacterial Toxins.
Funder
National Health and Medical Research Council
Funding Amount
$608,425.00
Summary
Inactivated bacterial toxins (toxoids), such as the tetanus vaccine, are safe and effective vaccines. Cholesterol dependent cytolysins (CDCs) are bacterial toxins produced by many important human pathogens including Group A Streptococcus (GAS) and Pneumococcus. GAS has no available vaccine and Pneumococcus does not have a universal vaccine. We have developed a new way of inactivating CDCs based on new knowledge of how they target human cells and will use this knowledge to make new vaccines.
Investigating The Consequences Of Dysregulated Lipogenesis In Cancer
Funder
National Health and Medical Research Council
Funding Amount
$600,647.00
Summary
Reprogramming of cellular metabolism is a hallmark of cancer. As such, there has been growing interest in developing strategies to exploit metabolism for therapeutic gain. Our ability to do this is dependent on a thorough understanding of the mechanisms by which dysregulation of cellular metabolism contributes to tumour progression. In this project, we seek to the investigate the fundamental mechanisms by which aberrant activation of lipid metabolism contributes to the tumourigenic process.
Reprogramming Human Fibroblasts Into Induced Trophoblast Stem Cells
Funder
National Health and Medical Research Council
Funding Amount
$889,064.00
Summary
We have been able to generate artificial human trophectoderm which is the tissue that creates the placenta. This will allow us to do research in how the genes control the fate of these cells without the need of human embryos or placenta. We anticipate that the derivation and characterising these cells will revolutionise placenta research, which in turn will contribute to the establishment of new therapies for placenta disease and infertility.
Advancing The Spatial Analysis Of Cells In Tissues To Profile The Tumour Microenvironment
Funder
National Health and Medical Research Council
Funding Amount
$187,918.00
Summary
Tumours are composed of a mix of different cells, including cancer cells, immune cells and other cells supporting tumour growth. These cells are not organised randomly, but rather are distributed in specific patterns. Here we will develop computational methods to detect these patterns and determine what statistical tests should be used to compare samples. This project will give us the tools to investigate how the location of cells in tissues relates to treatment response and survival.
Stopping Breast Cancer Progression By Targeting Tumour Stroma
Funder
National Health and Medical Research Council
Funding Amount
$772,877.00
Summary
Our latest research demonstrated that CRELD2 protein that is secreted by breast cancer cells alters normal cells surrounding tumour. CRELD2 represents an ideal therapeutic target as it is not important for normal cells and it is a secreted protein and thus can be targeted by numerous means. Successful completion of this research proposal will provide foundation to find new targets for combining therapies affecting both tumour and it's altered environment in breast and potentially other cancers.
Understanding The Molecular Mechanisms Of Cell Death In Radiotherapy
Funder
National Health and Medical Research Council
Funding Amount
$643,856.00
Summary
Radiotherapy (RT) is responsible for 40% of cancer cures. New technology enables RT delivery in fewer treatments using higher radiation dosages through a technique called 'ART'. While ART is effective in the clinic, the underlying mechanisms of cancer cell death are unclear. Here we show that ART induces two distinct waves of cancer cell death. We will characterize these waves of cell death and determine how to enhance tumour cell killing with pharmacological intervention.
Dendritic Cells Govern The Balance Between Immunity And Homeostasis To Inhaled Antigen
Funder
National Health and Medical Research Council
Funding Amount
$816,131.00
Summary
The development of better intranasal vaccines hinges on the improved understanding of how the immune response is initiated following vaccine delivery into the upper airways. In this project we will provide fundamental understanding of how immune responses to inhaled antigens are regulated; this considerable conceptual advance will lay the foundation for which new intranasally delivered immunotherapies will ultimately emerge.
Characterisation And Targeting T Cellular Metabolism To Improve Control Of Chronic Viral Infections
Funder
National Health and Medical Research Council
Funding Amount
$791,427.00
Summary
CD8+ T cells are the frontline warriors of our immune system that can eliminate infected or cancerous cells. However, diseases caused by overwhelming viral infections are associated with widespread impairments in immunity and cellular metabolism. Here, we propose to examine molecular pathways involved in cellular metabolism that could be utilized to improve therapies against viral infection and cancer.