Control Of Proteases In Infectious, Degenerative And Cardiovascular Disease
Funder
National Health and Medical Research Council
Funding Amount
$11,668,789.00
Summary
Proteases are enzymes that control key processes in humans. The research in this program will result in major discoveries in the field of proteases and their inhibitors, with a focus on inflammatory, cardiovascular and degenerative disease. The knowledge gained from this strong foundation of fundamental research will underpin the translational outcomes necessary to combat the debilitating effects of immunological dysfunction, conformational and cardiovascular disease.
Structural Biology Of Cytokine Receptor Signalling
Funder
National Health and Medical Research Council
Funding Amount
$3,988,996.00
Summary
This Program will be focused on a group of protein hormones and their receptors, implicated in blood cell cancers and inflammatory diseases and for which current treatments are inadequate. We will determine the mechanism of receptor activation and in particular will seek to link different forms of receptor assembly to different functions. This information will help us develop new drugs with more specificity for certain hormone functions and thus less side-effects.
The goal of the proposed Program is to improve treatments forpain, especially persistent pain, which remains a poorly managed global health burden. Our pre-eminent team integrates a unique set of complementary research skills in using peptides derived from venomous invertebrates to dissect the pharmacology of pain pathways in persistent pain states, and develop these novel peptides to the point where they can be considered for pre-clinical development in collaboration with commercial partners.
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
Type 2 diabetes (T2D) is threatening the health of this nation and if unchecked will cripple our health care system. There are several problems: (1) The incidence of T2D is growing and we do not fully know why; (2) T2D involves defective insulin action but how insulin works normally is still unclear; (3) much research in this area is performed in laboratory cells or animals and the translation of this research to the human disease is yet to be fully realised; and (4) current therapies and diagno ....Type 2 diabetes (T2D) is threatening the health of this nation and if unchecked will cripple our health care system. There are several problems: (1) The incidence of T2D is growing and we do not fully know why; (2) T2D involves defective insulin action but how insulin works normally is still unclear; (3) much research in this area is performed in laboratory cells or animals and the translation of this research to the human disease is yet to be fully realised; and (4) current therapies and diagnostic markers for early disease prediction are inadequate. Our goal is to make progress in each of these areas.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
MOLECULAR AND CELLULAR PATHOGENESIS OF HUMAN LIVER DISEASE
Funder
National Health and Medical Research Council
Funding Amount
$4,928,323.00
Summary
n humans, chronic liver diseases cause cirrhosis of the liver in some but not all individuals. This leads to protracted ill-health, complications (fluid retention in the abdomen, confusion, bloodstream infections, kidney failure, liver cancer) resulting in hospitalisation, liver transplantation and premature death. In Australia, cirrhosis is an important cause of death and of years of potential life lost, while liver cancer has recently doubled and is predicted to treble by 2020. The common caus ....n humans, chronic liver diseases cause cirrhosis of the liver in some but not all individuals. This leads to protracted ill-health, complications (fluid retention in the abdomen, confusion, bloodstream infections, kidney failure, liver cancer) resulting in hospitalisation, liver transplantation and premature death. In Australia, cirrhosis is an important cause of death and of years of potential life lost, while liver cancer has recently doubled and is predicted to treble by 2020. The common causes are hepatitis C, fatty liver disorders, alcohol and hepatitis B; when 2 of these are present together, there is a higher risk of cirrhosis. This program aims to unravel the pathological processes which cause cirrhosis at the molecular and cellular levels, in order to understand why some people are at higher risk. These processes could result from genetic predisposition, other constitutional factors (age, gender) or from lifestyle factors (overnutrition, inactivity, alcohol). The 3 chief investigators from Westmead s Millennium Institute and the Centenary Institute of Royal Prince Alfred Hospital are international experts in hepatitis C, non-alcoholic steatohepatitis (NASH) and other fatty liver disorders, autoimmune hepatitis, liver transplantation, and scarring processes that lead to cirrhosis of the liver. The new knowledge that will result from these studies will be used to help prevent people developing severe forms of chronic liver disease, and for treating cirrhosis if it has already occurred.Read moreRead less
Regulation Of Bone Resorption And Formation In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$5,596,183.00
Summary
Bone is continually being formed and broken down, and these two processes are critical forthe maintenance of a normal skeleton. These processes are dependent upon communication between the bone building and degrading cells, and the hormones growth factors and cytokines that are present in the circulation or produced in bone. The tightly regulated processes of bone formation and degradation need to remain equal, and are essential for the achievement and maintenance of skeletal strength and form. ....Bone is continually being formed and broken down, and these two processes are critical forthe maintenance of a normal skeleton. These processes are dependent upon communication between the bone building and degrading cells, and the hormones growth factors and cytokines that are present in the circulation or produced in bone. The tightly regulated processes of bone formation and degradation need to remain equal, and are essential for the achievement and maintenance of skeletal strength and form. Osteoporosis results from an excess of bone breakdown over formation, and our Program aims to identify the factors that regulate these processes, and develop new therapies that can modify them. We will also determine what it is about bone cell properties that make some cancers, especially those of breast and prostate, particularly prone to spread to bone.Read moreRead less
To understand the genetic basis of two of the most important cancers in women, breast and ovarian cancer. The team has already identified one gene that confers a very high risk of breast cancer and may account for a large proportion of 'familial' breast cancer. Their aim is to identify additional predisposition genes and to determine their normal function in the cell, as well as the way in which they contribute to the development of cancer
Determinants Of Child Health And Development: Populations, Partnerships, Pathways And Prevention
Funder
National Health and Medical Research Council
Funding Amount
$8,214,333.00
Summary
There are considerable challenges to the study of complex health and developmental problems in children and young people. Despite increasing prosperity in Australia, many of these problems are not abating and some appear to be increasing. These include low birthweight, behavioural and mental health problems, autism, obesity and, in Indigenous children, infections. This Program proposes investigating these problems with a view to prevention, thus meeting the national research priority of Promotin ....There are considerable challenges to the study of complex health and developmental problems in children and young people. Despite increasing prosperity in Australia, many of these problems are not abating and some appear to be increasing. These include low birthweight, behavioural and mental health problems, autism, obesity and, in Indigenous children, infections. This Program proposes investigating these problems with a view to prevention, thus meeting the national research priority of Promoting and Maintaining Good Health, particularly _a healthy start to life� and _preventive health care�. The Program is unique in that it brings together a multi-disciplinary team of researchers of international repute to investigate these complex issues. The research team comprises epidemiologists, clinicians, developmental psychologists, biostatisticians, sociologists and other social scientists. This team has a proven track record in producing research outcomes that have translated into innovative health policy and practice in areas as diverse as: - the use of folic acid in spina bifida prevention - understanding cerebral palsies - suicide prevention and mental health in children and young people - Aboriginal child health and development - intellectual disabilities including Rett syndrome and autism - in vitro fertilisation and birth defects. The factors influencing how children develop into young adults include genetic inheritance, nutrition and growth, and family, socioeconomic and environmental conditions. This work demands new ways of measuring and analysing these factors in populations of children and their families. Western Australia is one of only three sites in the world to have comprehensive linked health data on the whole of its population of children and their families. This Program comprises five overlapping themes of research planned around these unique population databases. The five themes are: - social, economic and psychological influences on child health and development - many paths to poor health are linked to social disadvantage. Examining these issues may explain why some childhood conditions are worsening or not improving - pathways to wellbeing, resilience and developmental disorders, including intellectual disability, autism, birth defects and cerebral palsy - nutrition and growth, particularly as it relates to low birthweight, childhood obesity and mental health - infectious disease, its causes and its influence on lifelong health problems and disabilities - Aboriginal health _ whilst spanning each of the research themes above, it presents its own unique challenges and requires it�s own unique solutions. This Program will investigate how children develop into young adults and will examine the influence of their families, nutrition and growth and socioeconomic and environmental conditions. It will develop new ways of measuring and analysRead moreRead less