Muscularskeletal Pain, Injury And Health: Improving Outcomes Through Conservative Management
Funder
National Health and Medical Research Council
Funding Amount
$8,123,518.00
Summary
Musculoskeletal pain and injury is a major health issue facing our ageing society. The cost in terms of health care and lost productivity is second only to cardiovascular disease. This Program will address the major musculoskeletal disorders such as spinal pain and osteoarthritis. The team will undertake research with the potential for real and enduring impact on these conditions - from the physiological basis for their occurrence, to trials of innovative drug-free conservative treatments.
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
The foot soldiers of the immune system, the white blood cells, constantly march through the body seeking out invaders, but kept in check by the barrier of endothelial cells that lines the inside of blood vessels. When infection occurs, molecular messages are transmitted amongst the white cells and between white cells and edothelium, to activate the immune cells to pass out of the blood vessels and mount a defence. Unfortunatley, the activation system sometimes goes awry, resulting in inflammator ....The foot soldiers of the immune system, the white blood cells, constantly march through the body seeking out invaders, but kept in check by the barrier of endothelial cells that lines the inside of blood vessels. When infection occurs, molecular messages are transmitted amongst the white cells and between white cells and edothelium, to activate the immune cells to pass out of the blood vessels and mount a defence. Unfortunatley, the activation system sometimes goes awry, resulting in inflammatory or allergic disease, such as arthritis or asthma. This team of researchers from the Hanson Institute in Adelaide, combining expertise in molecular and cell biology, protein chemestry, structual biology and animal models, has been working together for over 10 years, investigating the molecular mechanisms involved in controlling the formation and activities of blood vessels and white blood cells. This program seeks to further that understanding, and to develop drugs that have the potential of ameliorating the inflammatory condition.Read moreRead less
Insult, Injury And Recovery In Brain Disease: From Molecules To Therapeutic Outcome
Funder
National Health and Medical Research Council
Funding Amount
$8,215,611.00
Summary
When nerve cells are damaged, destroyed or injured, through disease or trauma, common pathological processes are set in train. Even though there are many factors that might trigger disease, these inevitably lead to common processes that end in cell death or initiate protective processes. One theme involves the factors that surround these responses to nerve injury and stress, and the consequent protective and regenerative responses that ensue. Another theme, closely integrates with the first, is ....When nerve cells are damaged, destroyed or injured, through disease or trauma, common pathological processes are set in train. Even though there are many factors that might trigger disease, these inevitably lead to common processes that end in cell death or initiate protective processes. One theme involves the factors that surround these responses to nerve injury and stress, and the consequent protective and regenerative responses that ensue. Another theme, closely integrates with the first, is to exploit basic biological mechanisms with the aim of identifying and developing therapeutic targets for the management of a wider range of neurological conditions.Read moreRead less
Regulation Of Neural Cell Production In The Normal And Diseased Brain
Funder
National Health and Medical Research Council
Funding Amount
$6,888,658.00
Summary
Members of this team are at the forefront of research into the molecular control of nerve cell production and function in the developing and adult brain. They were responsible, often through collaboration, for many of the major discoveries demonstrating that stem cells in the brain of adult animals can generate new nerve cells; this revolutionised our concept of the brain and opened-up the possibility of therapeutic repair of neural damage through stimulation of a patient?s own stem cells. Disco ....Members of this team are at the forefront of research into the molecular control of nerve cell production and function in the developing and adult brain. They were responsible, often through collaboration, for many of the major discoveries demonstrating that stem cells in the brain of adult animals can generate new nerve cells; this revolutionised our concept of the brain and opened-up the possibility of therapeutic repair of neural damage through stimulation of a patient?s own stem cells. Discovering the molecular mechanisms controlling this process is the goal of the present program. In order to achieve this aim we have formed a team on the basis of considerable past success, as well as future requirements. The team members have the complementary skills to assess all aspects of the problem, including crucial functional and clinical expertise. By combining resources we will position ourselves at the very forefront of the international competition to discover and to evaluate clinically the molecular mechanisms underlying neural repair and regeneration. This is of enormous significance in determining how we best treat stroke, injury and other neurodegenerative diseases in the next 10 years, and will lead to the development of new therapeutics of immense value. The team will use innovative approaches such as cell-sorting to obtain pure populations of stem cells and their progeny in order to identify new therapeutic targets; these will then be validated in animal models of neurological disease. Since team members have previously been involved in progressing molecular discovery to clinical trials, we are also in a good position to exploit these discoveries in partnership with the biopharmaceutical industry.Read moreRead less
Molecular Regulation Of Blood Cell Production And Function
Funder
National Health and Medical Research Council
Funding Amount
$18,333,174.00
Summary
The blood-forming system is an intricately controlled balance of cell proliferation, maturation and functional activity that is essential for oxygen transport throughout the body, blood clotting, and effective immune responses. Defining the genes and molecules that orchestrate blood cell production and function is crucial, not only for understanding the role of blood in health, but for establishing the bases of blood cell disorders such as autoimmunity and leukaemia, and for devising new clinica ....The blood-forming system is an intricately controlled balance of cell proliferation, maturation and functional activity that is essential for oxygen transport throughout the body, blood clotting, and effective immune responses. Defining the genes and molecules that orchestrate blood cell production and function is crucial, not only for understanding the role of blood in health, but for establishing the bases of blood cell disorders such as autoimmunity and leukaemia, and for devising new clinical strategies for fighting these lethal diseases. This program is conducted by a large, established team of investigators that have made world-class contributions to understanding blood cell formation and function for more than 30 years. Their work established the modern era of molecular haematology via discovery and analysis of blood cell hormones (colony-stimulating factors or CSFs), their receptors and intracellular mediators, which resulted in development of treatments for millions of cancer patients. The program is a multidisciplinary, team approach to fundamental biological questions with a focus on potential clinical and commercial outcomes involving collaborations with clinical medicine and the pharmaceutical industry. Research will focus on meshing novel genetic approaches in mice with translation studies in humans to identify new validated targets for therapeutic intervention in blood cell diseases, as well as building on the team s expertise in cytokine action with emphasis on the actions of the suppressor of cytokine signalling (SOCS) molecules, a key family of proteins that controls cytokine actions.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
Development And Refinement Of Neural Connections In The Adult Brain In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$8,061,596.00
Summary
Our group will use innovative approaches such as advanced imaging and cell-sorting and development of animal models to determine how new neurons are generated, how they travel to different parts of the brain and how they integrate into the existing brain circuitry. These discoveries will point to new ways in which to treat brain damage both during ageing and during pathology. Since team members have previously been involved in progressing molecular discovery to clinical trials, we are also in a ....Our group will use innovative approaches such as advanced imaging and cell-sorting and development of animal models to determine how new neurons are generated, how they travel to different parts of the brain and how they integrate into the existing brain circuitry. These discoveries will point to new ways in which to treat brain damage both during ageing and during pathology. Since team members have previously been involved in progressing molecular discovery to clinical trials, we are also in a good position to exploit these discoveries in partnership with the biopharmaceutical industry.Read moreRead less