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
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.
Molecular mechanisms regulating Ca2+ channels formed by Orai and STIM proteins. Store-operated calcium channels play a central role in the functions of all animal cells. They participate in generating the cellular responses to hormones, antigens, growth factors and other physiological stimuli. The aims of this project are to elucidate cellular mechanisms that regulate interaction between the molecular components of store-operated calcium channel, Orai and STIM. Using techniques of electrophysiol ....Molecular mechanisms regulating Ca2+ channels formed by Orai and STIM proteins. Store-operated calcium channels play a central role in the functions of all animal cells. They participate in generating the cellular responses to hormones, antigens, growth factors and other physiological stimuli. The aims of this project are to elucidate cellular mechanisms that regulate interaction between the molecular components of store-operated calcium channel, Orai and STIM. Using techniques of electrophysiology and molecular biology we expect to answer a fundamental question how STIM and Orai proteins interact to form functional store-operated calcium channels, and how the expression of STIM and Orai is regulated.Read moreRead less
Non-linear modelling for predicting patient presentation rates for mass-gatherings. Mass-gatherings are events where crowds gather. Access to health care at these events is critical, though difficult. Complex interrelationships exist between characteristics of events and presenting patient profiles. To prevent overwhelming local hospital and emergency services it is important to accurately predict patient volume. A predictive model constructed through linear modelling has been widely used. Key f ....Non-linear modelling for predicting patient presentation rates for mass-gatherings. Mass-gatherings are events where crowds gather. Access to health care at these events is critical, though difficult. Complex interrelationships exist between characteristics of events and presenting patient profiles. To prevent overwhelming local hospital and emergency services it is important to accurately predict patient volume. A predictive model constructed through linear modelling has been widely used. Key features affecting patient presentations are non-linear in character and non-linear modelling may provide more accurate patient predictive models. This project provides prospective analysis of data to develop a non-linear predictive model.Read moreRead less
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
Novel regulation of TRP channels by oxygen-dependent hydroxylation. Factor inhibiting HIF-1 (FIH-1) is an oxygen-sensing asparaginyl hydroxylase. A bioinformatic search identified specific transient receptor potential (TRP) ion channels as likely substrates. The hypothesis is that TRP channels are regulated by hypoxia, mediated through a novel mechanism of oxygen-dependent hydroxylation by FIH. The aim of this project is to investigate how hydroxylation by FIH mediates the hypoxic regulation of ....Novel regulation of TRP channels by oxygen-dependent hydroxylation. Factor inhibiting HIF-1 (FIH-1) is an oxygen-sensing asparaginyl hydroxylase. A bioinformatic search identified specific transient receptor potential (TRP) ion channels as likely substrates. The hypothesis is that TRP channels are regulated by hypoxia, mediated through a novel mechanism of oxygen-dependent hydroxylation by FIH. The aim of this project is to investigate how hydroxylation by FIH mediates the hypoxic regulation of TRP channels. Preliminary data show that the first candidate, TRPV3, is activated in hypoxia, is hydroxylated by FIH, and hydroxylation mediates changes in activity. Ion channels are important for the physiological response to hypoxia, and this project aims to define a novel mechanism for this response, with relevance to mammalian physiology.Read moreRead less