This program of research is firmly focussed on the basic mechanisms involved in normal functioning of cells and tissues, followed by a step by step process to understand the abnormal or the diseased. The disease states we are investigating involve the blood and blood vessels, and when there is malfunction it may contribute to conditions as diverse as atherosclerosis, thrombosis, inflammation and cancer. The program thus addresses the fundamentals of diseases which are responsible for most deaths ....This program of research is firmly focussed on the basic mechanisms involved in normal functioning of cells and tissues, followed by a step by step process to understand the abnormal or the diseased. The disease states we are investigating involve the blood and blood vessels, and when there is malfunction it may contribute to conditions as diverse as atherosclerosis, thrombosis, inflammation and cancer. The program thus addresses the fundamentals of diseases which are responsible for most deaths in our society. We will use technology which is proven to provide precise information, the molecular and biochemical processes responsible for cell function (or malfunction). However in each individual project there will be a clear path to a clinical use, diagnostic or therapeutic. Indeed in a number of the components of the program there are already potential treatments and diagnostics in development and trial.Read moreRead less
The Chief Investigators have worked as a team for 20 years as part of a successful NHMRC Program Grant that was renewed on three successive occasions and subsequently under a NHMRC Block Grant to QIMR. Their combined expertise covers the whole spectrum from the bedside to the bench with respect to clinical studies and fundamental molecular studies of iron homeostasis. The common theme of iron homeostasis and iron overload pervades virtually all the research of the team. The team�s research has l ....The Chief Investigators have worked as a team for 20 years as part of a successful NHMRC Program Grant that was renewed on three successive occasions and subsequently under a NHMRC Block Grant to QIMR. Their combined expertise covers the whole spectrum from the bedside to the bench with respect to clinical studies and fundamental molecular studies of iron homeostasis. The common theme of iron homeostasis and iron overload pervades virtually all the research of the team. The team�s research has led to fundamental observations of iron regulation and homeostasis and the development of guidelines for the management of, and screening for, haemochromatosis, recognized as the most common inherited disorder of Caucasian populations. The proposed research encompasses molecular studies aimed at deciphering the mechanisms of iron absorption and transport; how these processes are regulated; and clinical studies on patients diagnosed with haemochromatosis. The findings are particularly pertinent to the diagnosis, management and prevention of clinical haemochromatosis.Read moreRead less
Antibodies are made by B-cells and are essential for a functional immune system. B cells circulate in the body, and, when they encounter an invader, they mature into antibody-producing cells (ASC). A small proportion of the cells become “memory” cells with the potential to become ASC should the same infection occur in the future. This is the basis of vaccination. This program aims to understand how a B cell changes into an ASC. We aim eventually to be able to improve vaccines and understand dise ....Antibodies are made by B-cells and are essential for a functional immune system. B cells circulate in the body, and, when they encounter an invader, they mature into antibody-producing cells (ASC). A small proportion of the cells become “memory” cells with the potential to become ASC should the same infection occur in the future. This is the basis of vaccination. This program aims to understand how a B cell changes into an ASC. We aim eventually to be able to improve vaccines and understand diseases such as allergy, lupus, arthritis and leukaemia to develop novel therapies.Read moreRead less
Developmental Aspects Of Respiratory Inflammation, Allergy And Asthma
Funder
National Health and Medical Research Council
Funding Amount
$7,169,609.00
Summary
Asthma develops as a complex series of interactions between genetic susceptibility and environmental exposures occurring in early life. While many children grow out of asthma others do not and develop the chronic form of the disease that persists into adult life. Our research involves understanding why some susceptible children develop asthma and why this becomes chronic in some. We will undertake studies in children to find out how and why this occurs. A major part of our studies involve longit ....Asthma develops as a complex series of interactions between genetic susceptibility and environmental exposures occurring in early life. While many children grow out of asthma others do not and develop the chronic form of the disease that persists into adult life. Our research involves understanding why some susceptible children develop asthma and why this becomes chronic in some. We will undertake studies in children to find out how and why this occurs. A major part of our studies involve longitudinal studies in cohorts of children recruited before birth. Having the ability to study children as they grow and develop conditions such as allergies and asthma allows us to understand why these conditions occur and allow us to predict which children are likely to develop them. Our research Program also has a solid focus on Translational Research, in which we will use the findings from our basic science studies to develop and test new methods of preventing and of treating asthma. These studies will include new methods for preventing the development of allergies, preventing the damage done to the lungs by severe viral respiratory infections in early life and better methods of treating established allergic asthma by improving immunotherapy techniques. By its very nature, primary prevention of disease in young children is controversial and raises some interesting questions. As part of this Program we intend to initiate consultation and debate in public, academic, regulatory and industry circles. An important role for our Program is shifting the current emphasis away from treatment of established disease towards preventing disease occurring. This is the best way to decrease the health, social and economic burden of chronic diseases such as asthma.Read moreRead less
Proteases, Their Inhibitors And Receptors In Degenerative Disease
Funder
National Health and Medical Research Council
Funding Amount
$5,843,388.00
Summary
Many of the themes of this program are aimed at understanding the molecular basis of several important degenerative diseases that in particular affect the ageing population. These include osteoporosis, arthritis, periodontal disease, wasting diseases of muscle and inherited disorders such as antitrypsin deficiency. The five CI’s on this application have formed a collaborative network since 1996. Dr Whisstock is a bioinformatician and structural biologist with a research focus on the serpin super ....Many of the themes of this program are aimed at understanding the molecular basis of several important degenerative diseases that in particular affect the ageing population. These include osteoporosis, arthritis, periodontal disease, wasting diseases of muscle and inherited disorders such as antitrypsin deficiency. The five CI’s on this application have formed a collaborative network since 1996. Dr Whisstock is a bioinformatician and structural biologist with a research focus on the serpin superfamily of protease inhibitors and their protease partners. He is currently the scientific director of the Victorian Bioinformatics Consortium and an NHMRC Senior Research Fellow. Dr Bird is an NHMRC Senior Research Fellow who discovered the intracellular branch of the serpin superfamily and formulated the hypothesis that describes their function. A-Prof Mackie is a world expert in the field of musculoskeletal biology and pathology. Dr Bottomley is a Senior Logan Fellow and RD Wright Fellow whose research focuses upon how proteins misfold and lead to disease. Dr Pike is an enzymologist whose research area encompasses a wide range of bacterial and mammalian proteases involved in the pathology of human disease. Each individual in this team brings different skills which makes this a very important and powerful collaboration. The research is extensive and involves protein folding, enzyme kinetics, molecular modelling, structural biology, bioinformatics, cell biology and pathology, enzyme kinetics and drug design. Collectively the CI’s have a total of 154 papers since 1998, of which a third include two or more of the CI’s as co-authors. Currently the team holds over >$5 million in grant funding. The team is augmented by four P.I.s: Dr Buckle is a talented structural biologist; Dr Scott is a molecular cell biologist who holds an NHMRC CJ Martin Fellow; Dr Garcia de la Banda is a computer scientist based at Monash and Dr Grigoryev is a world expert in chromatin condensation based at Penn State University (USA).Read moreRead less
Tropical Infectious Diseases - Pathogenisis And Vaccine Research
Funder
National Health and Medical Research Council
Funding Amount
$7,311,989.00
Summary
The diseases on which three themes of the work proposed centre, malaria, streptococcal diseases and scabies are infectious diseases largely affecting indigenous people in various parts of the world on a massive scale, for which there are no vaccines. The aim of the work is to develop vaccines or other biological prevention measures against each of these diseases and the problems that need to be solved are similar. The team includes senior experts on thebiology of infectious diseases with long hi ....The diseases on which three themes of the work proposed centre, malaria, streptococcal diseases and scabies are infectious diseases largely affecting indigenous people in various parts of the world on a massive scale, for which there are no vaccines. The aim of the work is to develop vaccines or other biological prevention measures against each of these diseases and the problems that need to be solved are similar. The team includes senior experts on thebiology of infectious diseases with long histories of collaboration as well as younger members with impressive credentials that are new to the collaboration. The fourth theme of the work proposed is concerned with inventive new ways of making such vaccines by novelchemical methods. It has already been the subject of published collaborative work onstreptococcal disease and is equally applicable to the other themes.Read moreRead less
A major obstacle to the development of safer and more effective pain treatments is the poorly defined nature of the different pathways involved in chronic pain. The applicant team bring together a unique set of research expertise in using neurotoxins to define, at the molecular level, how the nervous system functions. The applicants also share a common interest in understanding and improving treatments for pain, especially chronic pain which continues to remain poorly managed Through a focus on ....A major obstacle to the development of safer and more effective pain treatments is the poorly defined nature of the different pathways involved in chronic pain. The applicant team bring together a unique set of research expertise in using neurotoxins to define, at the molecular level, how the nervous system functions. The applicants also share a common interest in understanding and improving treatments for pain, especially chronic pain which continues to remain poorly managed Through a focus on pain research, the Program will significantly enhance the scope of existing multidisciplinary collaborations between the Cis Lewis Alewood, Adams and Christie, which have already made a considerable impact in the fields of pharmacology and neuroscience. The CIs also have considerable experience in the development of pain therapeutics, having discovered two conopeptides now under commercial development with AMRAD (AM336) and Xenome Ltd (Xen2174). This Program will discover and use highly selective conopeptides such as these to dissect the pharmacology of peripheral pain pathways and their projections into the central nervous system, and to identify and characterise new targets amenable to drug intervention. The long-term goal of the Program is to discover new targets in pain pathways and develop conopeptides that act on these targets in animal models of chronic pain. These molecules will be optimised within the Program to the point where they can be considered for pre-clinical development in collaboration with commercial partners.Read moreRead less
This Program Grant investigates a number of important reproductive problems that affect the fertility of men, prostate cancer and the way the mother nurtures and protects the baby during pregnancy. The successful development of sperm requires the proper function of a number of biological processes. This grant investigates the way in which sperm are produced, the genes that are needed to control their development, and the way sperm propel themselves and fertilize the egg. The research also invest ....This Program Grant investigates a number of important reproductive problems that affect the fertility of men, prostate cancer and the way the mother nurtures and protects the baby during pregnancy. The successful development of sperm requires the proper function of a number of biological processes. This grant investigates the way in which sperm are produced, the genes that are needed to control their development, and the way sperm propel themselves and fertilize the egg. The research also investigates how sperm are protected during their development from infection and immunological rejection, achieved in part by a special environment within the tubes in the testis where they grow. It appears that the general mechanisms that the body uses to combat infections are modified within the testis and the way in which this occurs may provide clues that could be applied to prevent the rejection of transplanted organs in general. Some of the substances that control these processes appear to play an important role in the body�s defense against infection. The grant also investigates the processes that are involved in the development of prostate cancer. These changes can occur over many years and the grant will study some substances that appear to be involved. The work will provide new knowledge that may assist in new tests to identify whether a cancer is slow or fast growing, thereby helping each man to decide the most sensible form of treatment. The grant will investigate how a group of proteins, that also are involved in the control of processes discussed above, assist the mother in protecting her baby during pregnancy. The outcomes will assist in the management of disturbances of pregnancy that may put the fetus at risk of survival.Read moreRead less