Mathematical and statistical methods for modelling invivo pathogen dynamics. This project aims to develop mathematical models and Bayesian statistical methods that better capture how natural defence responses and drugs help control infection. When viruses (e.g. influenza) or parasites (e.g. malaria) invade the human body, they begin to replicate. To date, only simple mathematical models have been developed to capture these processes, and these models are not well formulated. This project will im ....Mathematical and statistical methods for modelling invivo pathogen dynamics. This project aims to develop mathematical models and Bayesian statistical methods that better capture how natural defence responses and drugs help control infection. When viruses (e.g. influenza) or parasites (e.g. malaria) invade the human body, they begin to replicate. To date, only simple mathematical models have been developed to capture these processes, and these models are not well formulated. This project will improve biomathematics and biostatistical algorithms for pathogen dynamics and is ultimately expected to benefit public health and clinical research aimed at alleviating the effect of infectious diseases on human health.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE170100785
Funder
Australian Research Council
Funding Amount
$345,491.00
Summary
Mathematical and statistical modelling of antimalarial drug action. This project aims to develop a mathematical model to optimise global antimalarial treatment policy. Malaria-causing parasites are resistant to the most potent antimalarial drug available. If left unaddressed, a catastrophic rise in global malaria incidence and mortality could occur. Changes to global antimalarial treatment policy increasingly rely on mathematical models, but they do not encompass recent breakthroughs in antimala ....Mathematical and statistical modelling of antimalarial drug action. This project aims to develop a mathematical model to optimise global antimalarial treatment policy. Malaria-causing parasites are resistant to the most potent antimalarial drug available. If left unaddressed, a catastrophic rise in global malaria incidence and mortality could occur. Changes to global antimalarial treatment policy increasingly rely on mathematical models, but they do not encompass recent breakthroughs in antimalarial drug action and the immune response. This project’s model is expected to improve antimalarial drug dosing regimens and control the spread of antimalarial drug resistance.Read moreRead less
An interdisciplinary approach to host-pathogen interactions in infection. This project aims to understand the molecular and cellular interactions between host and parasite, as well as providing a quantitative framework for analysing infection dynamics in other systems. Infection involves a complex interaction between the host and the parasite, which is very dynamic and therefore difficult to study by traditional sampling and analysis approaches. This project has combined mathematical modelling w ....An interdisciplinary approach to host-pathogen interactions in infection. This project aims to understand the molecular and cellular interactions between host and parasite, as well as providing a quantitative framework for analysing infection dynamics in other systems. Infection involves a complex interaction between the host and the parasite, which is very dynamic and therefore difficult to study by traditional sampling and analysis approaches. This project has combined mathematical modelling with a novel experimental protocol to allow the study of kinetics of parasite replication in vivo. Expected outcomes will provide significant benefits, such as new avenues for vaccination and immune intervention.Read moreRead less
Multiscale models in immuno-epidemiology. The spread of a pathogen (for example, a virus or bacteria) through a population is a multi-scale phenomena, influenced by factors acting at both the population and within-host scales. At the population scale, transmission is influenced by how infectious an infected host is. Infectiousness in turn depends on the balance between pathogen replication within the host and immune/drug control mechanisms. This project aims to develop new mathematical framework ....Multiscale models in immuno-epidemiology. The spread of a pathogen (for example, a virus or bacteria) through a population is a multi-scale phenomena, influenced by factors acting at both the population and within-host scales. At the population scale, transmission is influenced by how infectious an infected host is. Infectiousness in turn depends on the balance between pathogen replication within the host and immune/drug control mechanisms. This project aims to develop new mathematical frameworks for simultaneously modelling these two scales. This will provide a platform for the rigorous study of complex biological interactions - such as the emergence and combat of drug-resistance - that shape society's ability to control infectious diseases in human, animal and plant systems.Read moreRead less
Chemical probes for the study of a unique enzyme from Mycobacterium tuberculosis. The design and chemical synthesis of molecules that selectively inhibit pathogen-specific enzymes is a validated approach toward new therapeutic agents. Mycobacterium tuberculosis contains a unique cytochrome P450 enzyme that catalyses an unusual chemical transformation to generate the product mycocyclosin. This research project will synthesise chemical probes to study the mechanism of this enzyme and the biologica ....Chemical probes for the study of a unique enzyme from Mycobacterium tuberculosis. The design and chemical synthesis of molecules that selectively inhibit pathogen-specific enzymes is a validated approach toward new therapeutic agents. Mycobacterium tuberculosis contains a unique cytochrome P450 enzyme that catalyses an unusual chemical transformation to generate the product mycocyclosin. This research project will synthesise chemical probes to study the mechanism of this enzyme and the biological role of mycocyclosin. Selective inhibitors of the enzyme will be developed, which will provide a foundation for the exploitation of these molecules in cellular research and medicine.Read moreRead less
Rational design of new drug candidates for the treatment of Trypanosoma cruzi infection. There is a serious shortage of safe and effective drugs to treat Chagas disease which is caused by a parasitic infection. This project aims to design and identify new drug candidates by defining the disposition profile within the body which is necessary to achieve a therapeutic effect.
Translating pharmacokinetic and pharmacodynamic data to better design new drugs for the treatment of Trypanosoma cruzi infection. New drugs to treat T. cruzi infection are urgently needed, however their design has been hampered by an incomplete understanding of complex host-parasite interactions, inadequate in vitro and in vivo tools to rigorously define activity during drug discovery, and a poor appreciation of concentration/effect relationships. This project aims to develop new and much needed ....Translating pharmacokinetic and pharmacodynamic data to better design new drugs for the treatment of Trypanosoma cruzi infection. New drugs to treat T. cruzi infection are urgently needed, however their design has been hampered by an incomplete understanding of complex host-parasite interactions, inadequate in vitro and in vivo tools to rigorously define activity during drug discovery, and a poor appreciation of concentration/effect relationships. This project aims to develop new and much needed in vitro methods to better define the kinetic and dynamic activity of new drug candidates, and will provide a rational basis for translating this information into lengthy animal models of T. cruzi infection. The outcome aims to be rationally designed drug candidates that are available in a shorter period of time and are suitable for further development.Read moreRead less
Australian Laureate Fellowships - Grant ID: FL150100106
Funder
Australian Research Council
Funding Amount
$2,951,945.00
Summary
Bio-metrology and modelling of a complex system: the malaria parasite. Bio-metrology and modelling of a complex system: the malaria parasite: This fellowship project aims to develop a cross-disciplinary program to measure, model and manipulate a complex cellular system — sexual differentiation of the human malaria parasite. Combining life and physical sciences with powerful imaging techniques, the project seeks to develop quantitative biochemical, biophysical and modelling techniques to probe a ....Bio-metrology and modelling of a complex system: the malaria parasite. Bio-metrology and modelling of a complex system: the malaria parasite: This fellowship project aims to develop a cross-disciplinary program to measure, model and manipulate a complex cellular system — sexual differentiation of the human malaria parasite. Combining life and physical sciences with powerful imaging techniques, the project seeks to develop quantitative biochemical, biophysical and modelling techniques to probe a complex system in a way previously not possible. It expects to integrate and correlate thousands of measurements of the dynamic processes inside cells and use these datasets to generate rigorous and sophisticated mathematical models that can predict drivers of commitment for transformation of the parasite to a sexual phase in preparation for transmission to mosquitoes. This holistic approach hopes to deliver new biotechnology and biomedical outcomes, including new ways to combat disease in livestock and humans.Read moreRead less
How auto-transporter proteins mediate bacterial interactions. This project aims to investigate the structure-function relationships that underpin key auto-transporter roles in bacterial cell adhesion, aggregation and biofilm formation. Auto-transporter proteins are extremely common in bacteria where they play a central role in controlling bacterial interactions with other bacteria, with human cells, and with surfaces. This project will define the molecular mechanisms underlying these processes. ....How auto-transporter proteins mediate bacterial interactions. This project aims to investigate the structure-function relationships that underpin key auto-transporter roles in bacterial cell adhesion, aggregation and biofilm formation. Auto-transporter proteins are extremely common in bacteria where they play a central role in controlling bacterial interactions with other bacteria, with human cells, and with surfaces. This project will define the molecular mechanisms underlying these processes. This will have significant benefits, such as providing the basis for the development of approaches to block auto-transporter functions that contribute to the establishment of persistent and difficult to treat bacterial infections.Read moreRead less
Cellular Organisation of Protective Immune Responses. Our immune system consists of a task force of white blood cells that coordinate to defeat invading pathogens. Research has revealed a cell receptor, CXCR3, controls immune cell interactions, which determine immune control and protection during initial cell activation and viral infection. This project will use a multi-disciplinary approach combining viral immunology, unique mouse models, advanced imaging, and bioinformatic analyses to dissect ....Cellular Organisation of Protective Immune Responses. Our immune system consists of a task force of white blood cells that coordinate to defeat invading pathogens. Research has revealed a cell receptor, CXCR3, controls immune cell interactions, which determine immune control and protection during initial cell activation and viral infection. This project will use a multi-disciplinary approach combining viral immunology, unique mouse models, advanced imaging, and bioinformatic analyses to dissect the cellular conversations that underpin immune protection. Revealing the mechanisms of cellular interactions during an immune response will have a major impact on development of targeted vaccines, and therapeutics (particularly for chronic infections and cancer), which are major health burdens.Read moreRead less