Investigating the evolution of innate and adaptive cellular immunity. This proposal aims to assess the impact of geographical and genetic isolation of the Australian Indigenous population on adaptive and innate immune systems. The project will use novel DNA sequencing approaches to generate the high resolution sequences of two genetic loci that regulate innate and adaptive immune responses, the major histocompatibility complex locus and the killer cell immunoglobulin-like receptor locus. In an i ....Investigating the evolution of innate and adaptive cellular immunity. This proposal aims to assess the impact of geographical and genetic isolation of the Australian Indigenous population on adaptive and innate immune systems. The project will use novel DNA sequencing approaches to generate the high resolution sequences of two genetic loci that regulate innate and adaptive immune responses, the major histocompatibility complex locus and the killer cell immunoglobulin-like receptor locus. In an initial screen, distinct variants and combinations of these genes were identified. This project aims to interrogate how variation in these critical genes impacts on the function of cytotoxic lymphocytes, providing insights into the evolutionary drivers of immune recognition mechanisms.Read moreRead less
The Molecular Basis of Nanoparticle Resistance in Mixed-Species Biofilm. The project aims to understand how the globally significant mixed-species growth of pathogens develop resistance to silver nanoparticle, currently one of the most important alternative antimicrobials to antibiotics. The integrated research is to elucidate, for the first time, the nanoparticle multi-targeting toxicity on mixed-species bacterial community and how, in turn, the bacteria activate their cell-to-cell signalling f ....The Molecular Basis of Nanoparticle Resistance in Mixed-Species Biofilm. The project aims to understand how the globally significant mixed-species growth of pathogens develop resistance to silver nanoparticle, currently one of the most important alternative antimicrobials to antibiotics. The integrated research is to elucidate, for the first time, the nanoparticle multi-targeting toxicity on mixed-species bacterial community and how, in turn, the bacteria activate their cell-to-cell signalling for a synergistic defence to adapt to the nanoparticle toxicity. The pioneering knowledge is the foundation for technologies targeting the interspecies metabolite cross-talking to overcome the resistance phenomena, ensuring a long-term efficacy of the alternative antimicrobial on the difficult-to-control pathogenic growth.Read moreRead less
How we remember and misremember traumatic experiences. The project addresses a significant and important problem: the role of memory distortion in Post Traumatic Stress Disorder (PTSD), a global disorder with significant personal, societal and economic costs. The aim of this project is to empirically investigate the extent, causes and triggering conditions of errors in memory for traumatic experiences; particularly exaggeration of these memories, which has been linked to poor psychological adjus ....How we remember and misremember traumatic experiences. The project addresses a significant and important problem: the role of memory distortion in Post Traumatic Stress Disorder (PTSD), a global disorder with significant personal, societal and economic costs. The aim of this project is to empirically investigate the extent, causes and triggering conditions of errors in memory for traumatic experiences; particularly exaggeration of these memories, which has been linked to poor psychological adjustment. Understanding how people exposed to trauma remember, and misremember, aspects of their experiences in ways that influence their recovery is both theoretically and practically important. Indeed, it will help us refine theory and identify possible points of intervention for PTSD sufferers.Read moreRead less
Human Leukocyte Antigen-A and -B regulation of Natural Killer cell function. The aim of this project is to determine how genetic variation in the genes encoding cell surface receptors expressed by innate lymphocytes and the molecules they recognise diversifies their capacity to sense and respond to infection. This knowledge is critical for understanding why there are intrinsic differences between individuals with respect to their capacity to respond to different types of infection and will ultim ....Human Leukocyte Antigen-A and -B regulation of Natural Killer cell function. The aim of this project is to determine how genetic variation in the genes encoding cell surface receptors expressed by innate lymphocytes and the molecules they recognise diversifies their capacity to sense and respond to infection. This knowledge is critical for understanding why there are intrinsic differences between individuals with respect to their capacity to respond to different types of infection and will ultimately inform our capacity to better deploy personalised medicines.Read moreRead less
Molecular mechanisms of catalysis and the basis of substrate specificity in polysaccharide hydrolases. Reaction intermediates along hydrolytic pathways and molecular determinants of substrate specificity of barley B-glucan exo- and endohydrolases will be defined using crystallographic and kinetic analyses. These enzymes are of central importance in cell wall metabolism during development of higher plants, and in plant-pathogen interactions. Realization of the project objectives will not only pro ....Molecular mechanisms of catalysis and the basis of substrate specificity in polysaccharide hydrolases. Reaction intermediates along hydrolytic pathways and molecular determinants of substrate specificity of barley B-glucan exo- and endohydrolases will be defined using crystallographic and kinetic analyses. These enzymes are of central importance in cell wall metabolism during development of higher plants, and in plant-pathogen interactions. Realization of the project objectives will not only provide fundamental information on catalytic mechanisms, but will also provide opportunities to manipulate enzyme specificity. Further, site-directed mutagenesis of the enzymes will be used to generate glycosynthases, which will be evaluated for their ability to synthesise novel oligosaccharide and polysaccharide products, some of which might show immunomodulating activity.Read moreRead less
Toll Like Receptor signalling as a mediator of sex differences in pain, opioid and alcohol action. Brain immunology will be examined in this project to see if the signalling of a receptor called Toll Like Receptor 4 can explain sex differences in pain, and the action of pain killers and alcohol. These findings will have significant implications on the understanding of male and female brains, and will assist in the design of new drugs to treat brain and spinal cord diseases.
Huntingtin-associated protein 1 controls cell communication. The purpose of this study is to identify the mechanisms by which a novel regulator of cell communication which we have identified is able to control the release of chemical signals from a cell. This project will provide critical insight into a cellular pathway that underlies hormone secretion, neurotransmission and higher brain functions.
New methods for integrating population structure and stochasticity into models of disease dynamics. Epidemics, such as the 2007 equine 'flu outbreak and 2009 swine 'flu pandemic, highlight the need to make informed decisive responses. This project will develop new methods that incorporate two important aspects of disease dynamics---host structure and chance---into mathematical models, and determine their impact in terms of controlling infections.
A shipload of consequences: studying the impact of Old World diseases on native South American populations via ancient DNA. This pioneering project will give the first real-time picture of the genetic changes induced by epidemics in human populations. This will reveal important new information about the likely impact of future epidemics on the genetic diversity of the immune system in modern human populations and will be of substantial use in building epidemiological models. By proposing to comb ....A shipload of consequences: studying the impact of Old World diseases on native South American populations via ancient DNA. This pioneering project will give the first real-time picture of the genetic changes induced by epidemics in human populations. This will reveal important new information about the likely impact of future epidemics on the genetic diversity of the immune system in modern human populations and will be of substantial use in building epidemiological models. By proposing to combine state-of-the-art science with global problems of humanity, we will address Australia's interests in expanding scientific expertise beyond its borders and place Australia at the leading edge of disease impact studies.Read moreRead less
Investigation of the fundamental roles of class Ib MHC (major histocompatibility complex) molecules in immunity. The proposed research program, using laboratory-based and synchrotron-based radiation, will provide insight into the roles of a poorly understood class of immune molecules. This will improve our understanding of the regulation of immunity, and the knowledge gained will increase Australia's international research profile.