Roles Of The Peptide Hormone, Ghrelin, In The Spinal Cord
Funder
National Health and Medical Research Council
Funding Amount
$414,326.00
Summary
This study investigates the control of internal organs of the body, the heart, blood vessels, intestine and bladder. We have made the new and surprising discovery that ghrelin, previously known to be a hormone, is probably also a neurotransmitter in the spinal cord. This raises the possibility that drugs that act on ghrelin receptors in the spinal cord could be used to treat high blood pressure or other problems of internal organs.
Genetic Variation And Host-parasite Interactions Of Sarcoptes Scabiei
Funder
National Health and Medical Research Council
Funding Amount
$294,536.00
Summary
Scabies is a disease of skin caused by the burrowing of the 'itch' mite Sarcoptes scabiei. Although up to 45 different host species can be infested by this mite, this organism is currently classified as a single species existing as multiple strains or varieties. Previous studies have failed to identify any structural differences between host-associated populations, suggesting a single gene pool. Our recent molecular study of scabies in people and dogs, from Aboriginal communities in the Northern ....Scabies is a disease of skin caused by the burrowing of the 'itch' mite Sarcoptes scabiei. Although up to 45 different host species can be infested by this mite, this organism is currently classified as a single species existing as multiple strains or varieties. Previous studies have failed to identify any structural differences between host-associated populations, suggesting a single gene pool. Our recent molecular study of scabies in people and dogs, from Aboriginal communities in the Northern Territory and the North and South Americas, using DNA fingerprinting techniques, suggested mites cluster by host species with no evidence of cross-transmission. However although this data seems to suggest that these sub-species deserve species status, another molecular study suggests Sarcoptes is a single species, presumably a result of interbreeding. Understanding interbreeding between populations is important in the control of the disease and in controlling resistance to acaricides. We wish to further characterise the genetic separation of different 'strains' or populations of mites by studying the evolutionary gene flow between host-associated populations. We will use a mitochondrial DNA marker that will clarify fine scale transmission processes and more clearly delineate the biological species status of S. scabiei. Recent in vitro data and clinical evidence in a patient with severe crusted scabies indicated resistance to ivermectin, the treatment of choice for these patients. We will investigate the role and genetic mechanisms of ivermectin resistance. This is important for future control programs, as acaricide resistance can spread rapidly in parasite populations.Read moreRead less
Investigating The Molecular Basis Of Emerging Drug Resistance In Scabies Mites
Funder
National Health and Medical Research Council
Funding Amount
$516,000.00
Summary
Scabies is a disease of the skin caused by the burrowing of the 'itch' mite Sarcoptes scabiei. In remote Aboriginal communities in northern and central Australia up to 60% of children can be infected. Scabies causes intense itching of the skin, resulting in skin damage through scratching, and serious secondary bacterial infections leading to kidney and heart disease. Some remote communities in the NT are documented to have the highest rates of kidney and heart disease in the world. The location ....Scabies is a disease of the skin caused by the burrowing of the 'itch' mite Sarcoptes scabiei. In remote Aboriginal communities in northern and central Australia up to 60% of children can be infected. Scabies causes intense itching of the skin, resulting in skin damage through scratching, and serious secondary bacterial infections leading to kidney and heart disease. Some remote communities in the NT are documented to have the highest rates of kidney and heart disease in the world. The location of the Menzies School of Health Research in this region where scabies is endemic has enabled us to undertake a number of studies on the disease. Our world first molecular study using microsatellite markers demonstrated that scabies mites on people were genetically distinct from those on dogs. This had important implications in control programs in the communities. Additional work has focused on laboratory studies to monitor the sensitivity of mites to current treatments used in community control programs and for the treatment of crusted scabies, a very severe and debilitating form of the disease. We have reported evidence of increasing resistance of scabies mites to topical 5%permethrin and documented both in vitro and clinical evidence of resistance to oral ivermectin. We now seek support to extend this work to identify at the molecular level the mechanisms of resistance and use this knowledge to design a diagnostic test. This work has both local and global implications. Scabies is a significant disease of children primarily in many indigenous and third world communities, as well as associated with nursing homes and HIV infection. The tools developed in this project will enable the assessment of drug treatment failures and assist in the development of more sensitive methods for monitoring resistance in the community, including the potential for reversing it. This will avoid the current global problems of resistance observed in other organisms such as headlice.Read moreRead less
Scabies is a significant disease of children particularly in indigenous communities. This project is aimed at working out how scabies mites resist medications used to treat them and to design a test for drug resistance. The tools developed in this project will enable the assessment of treatment failures and assist in the development of more sensitive methods for monitoring resistance in the community, including the potential for reversing it.
Adipose Triglyceride Lipase: Regulation And Implications For The Aetiology Of Insulin Resistance
Funder
National Health and Medical Research Council
Funding Amount
$323,453.00
Summary
Obese individuals have elevated fat levels in the blood and muscle, which contributes to the development of other diseases such as type 2 diabetes. A newly discovered protein named adipose triglyceride lipase (ATGL) is essential for fat breakdown. This project aims to identify how ATGL operates and determine whether defective ATGL function leads to type 2 diabetes. These studies will assist in the development of strategies aimed at reducing fatty acids in blood and muscle.
DNA-binding proteins regulate gene expression to co-ordinate our development and physiology. These proteins operate by recognizing specific control sequences in target genes and turning these genes on or off. It may be possible to artificially regulate specific genes to treat certain inherited disorders. One of the most common genetic diseases worldwide is inherited haemoglobinopathy. Mutations in the adult beta haemoglobin gene cause diseases such as sickle cell anaemia and beta thalassaemia. T ....DNA-binding proteins regulate gene expression to co-ordinate our development and physiology. These proteins operate by recognizing specific control sequences in target genes and turning these genes on or off. It may be possible to artificially regulate specific genes to treat certain inherited disorders. One of the most common genetic diseases worldwide is inherited haemoglobinopathy. Mutations in the adult beta haemoglobin gene cause diseases such as sickle cell anaemia and beta thalassaemia. These diseases can be seriously debilitating or lethal and often require lifelong treatment. Current treatments (such as repeated blood transfusion and subsequent iron chelation therapy) are demanding on the patient, expensive, and in the long run can be inneffective. Proposed future treatments involve reactivating normally silent haemoglobin genes (such as foetal haemoglobin) to compensate for the absence of adult beta haemoglobin. We have been studying a DNA-binding protein termed BKLF. We have shown that BKLF turns genes off and in particular we have shown using mammalian model systems that BKLF turns off the foetal haemoglobin gene. Inhibiting BKLF action therefore becomes an important goal, as this might lead to a reactivation of foetal haemoglobin to alleviate sickle cell anaemia and beta thalassaemia. We are seeking to understand the molecular mechanisms by which BKLF silences gene expression, to identify other proteins with which it operates, and to define their activities, in an effort to identify the best ways of inhibiting BKLF's action. Ultimately, studies on defined model genes such as the haemoglobin genes should elucidate general principles of gene regulation that may be useful in controlling gene expression in additional therapeutic or experimental contexts.Read moreRead less
Characterisation Of A Novel Porphyromonas Gingivalis Regulatory Protein That Controls Virulence Related Gene Expression
Funder
National Health and Medical Research Council
Funding Amount
$569,620.00
Summary
In this study we will characterise the manner in which genes essential for the virulence of Porphyromonas gingivalis, a bacterium associated with chronic periodontitis, are regulated. This will provide information on how this bacterium causes disease and may offer opportunities for the development of new treatment strategies.
Transcriptome Profiling Of The Human Pathogen Schistosoma Japonicum
Funder
National Health and Medical Research Council
Funding Amount
$257,560.00
Summary
The parasitic disease, schistosomiasis, caused by human bloodflukes of the genus Schistosoma, is a major public health issue in Africa, Latin America and South East Asia. Current control methods are far from ideal, and a comprehensive understanding of the genetic mechanisms which allow schistosomes to grow, develop and survive within their hosts affords the best prospect for identifying new drug and vaccine targets. Microarray technology allows simultaneous monitoring of thousands of different g ....The parasitic disease, schistosomiasis, caused by human bloodflukes of the genus Schistosoma, is a major public health issue in Africa, Latin America and South East Asia. Current control methods are far from ideal, and a comprehensive understanding of the genetic mechanisms which allow schistosomes to grow, develop and survive within their hosts affords the best prospect for identifying new drug and vaccine targets. Microarray technology allows simultaneous monitoring of thousands of different genes, and to determine where and when they are active, thus placing the mass of data generated by genome sequencing programs into a biological and functional context. Microarrays provide a unique, cutting-edge, tool for investigating schistosome biology. We have fabricated a microarray representing some 20,000 schistosome genes. We will use this resource to perform large scale monitoring of schistosome gene expression during the parasite's complex life cycle, targetting the regionally important Asian schistosome, Schistosoma japonicum, for study. This will provide the single largest insight into the genetic changes that occur during schistosome development, will greatly further our understanding of the adaptations needed for the growth, development and survival of the parasite, and will identify genes involved in key biological processes, all of which may be exploitable for future interventions and treatments.Read moreRead less