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
Innovative mathematical modelling to determine incorporation of gene therapy in different cell lineages; Human Immunodeficiency Virus (HIV) as a model setting. Gene therapy is a promising therapeutic that is being developed to address genetic diseases and viral infections such as Human Immunodeficiency Virus (HIV). This project will produce mathematical models of how gene therapy delivered to one type of cell can differentiate into the desired end target and impact disease.
Structural studies of host-pathogen interactions. The host-pathogen interface represents a major frontier for biomedical and biotechnological applications. This project aims to understand at the atomic level two such interfaces. In the first instance, the project will elucidate the molecular basis for inhibition of premature host cell death by poxviruses, in particular vaccinia and variola virus, the causative agent of smallpox. In the second instance, the aim is to understand how defensins, a ....Structural studies of host-pathogen interactions. The host-pathogen interface represents a major frontier for biomedical and biotechnological applications. This project aims to understand at the atomic level two such interfaces. In the first instance, the project will elucidate the molecular basis for inhibition of premature host cell death by poxviruses, in particular vaccinia and variola virus, the causative agent of smallpox. In the second instance, the aim is to understand how defensins, a major class of host defence molecules, recognise microbial targets such as fungi, and exert a potent antimicrobial effect. Understanding the precise molecular mechanisms operating at both these host-pathogen interfaces this will provide novel avenues for the design of antiviral and antimicrobial agents.Read moreRead less
The ins and outs of HIV biology. This project aims to delineate the fundamental mechanisms that regulate the production of HIV and the ability of HIV to cause AIDS in infected patients. It will utilise state-of-the-art technologies to unearth new clues that govern the biology of HIV, with the ultimate goal to develop novel vaccine and treatment strategies against HIV.
Complement evasion strategies of malaria parasites. Pathogens have evolved to protect themselves from deleterious effects of host immune attack. Malaria is one of the most widespread parasitic diseases, yet evasion strategies employed by these parasites are unknown. This project will aim to understand how malaria parasites exploit the innate immune system for successful human infection.
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
How Bacteria Fold Virulence Factors to Cause Disease. Bacteria use folding enzymes to assemble proteins essential for cell integrity and pathogenicity. These foldases include the Disulphide bridge proteins, which catalyse the introduction of disulfide bonds. This project will study two important human pathogens, Salmonella Typhimurium and uropathogenic Escherichia coli, to address the fundamental and poorly understood questions of diversity of Dsb networks across bacterial pathogens and the role ....How Bacteria Fold Virulence Factors to Cause Disease. Bacteria use folding enzymes to assemble proteins essential for cell integrity and pathogenicity. These foldases include the Disulphide bridge proteins, which catalyse the introduction of disulfide bonds. This project will study two important human pathogens, Salmonella Typhimurium and uropathogenic Escherichia coli, to address the fundamental and poorly understood questions of diversity of Dsb networks across bacterial pathogens and the role of these foldases in virulence. The research will reveal how bacterial virulence factors are folded, identify novel targets for therapeutic intervention and provide the basis for structure-based design on new antimicrobials in the future. Read moreRead less
Unraveling autotransporter function in bacterial aggregates and biofilms. Autotransporters are a large family of bacterial proteins that play a central role in pathogenesis. They promote the formation of cell clusters and biofilms, which are mechanisms for bacterial resistance to host immune factors and antibiotics. Currently, the precise mode of action of autotransporters is unknown. This project will examine the interplay between the structure and function of key autotransporter proteins. It ....Unraveling autotransporter function in bacterial aggregates and biofilms. Autotransporters are a large family of bacterial proteins that play a central role in pathogenesis. They promote the formation of cell clusters and biofilms, which are mechanisms for bacterial resistance to host immune factors and antibiotics. Currently, the precise mode of action of autotransporters is unknown. This project will examine the interplay between the structure and function of key autotransporter proteins. It is expected that the outcomes of this research will establish how these proteins mediate aggregation and biofilm formation. It may also provide three-dimensional structures of proteins that are strongly immunogenic and may represent targets for future vaccine design, as well as identify molecules that inhibit autotransporter function.Read moreRead less
Bioactive Peptides as Pharmacological Tools and Novel Drug Leads. Bioactive peptides are produced by all organisms and play numerous critical physiological roles, including in cellular communication, host defence and capture of prey. Peptides have huge potential as tools for studying roles of signalling pathways and as novel drugs due to their high affinity and selectivity for various therapeutically relevant targets. However their use has been limited by poor in vivo stability. This project is ....Bioactive Peptides as Pharmacological Tools and Novel Drug Leads. Bioactive peptides are produced by all organisms and play numerous critical physiological roles, including in cellular communication, host defence and capture of prey. Peptides have huge potential as tools for studying roles of signalling pathways and as novel drugs due to their high affinity and selectivity for various therapeutically relevant targets. However their use has been limited by poor in vivo stability. This project is focused on studying structural features of a range of peptides and their contributions to both activity and to resistance against degradation, with the aim to develop stabilised bioactive peptide sequences for in vivo applications, allowing the full potential of peptides as drugs to be realised.Read moreRead less