Understanding G Protein-Coupled Receptors (GPCRs): Accelerating Discovery From Concept To Clinic.
Funder
National Health and Medical Research Council
Funding Amount
$6,871,789.00
Summary
G Protein-Coupled Receptors (GPCRs) form the largest family of receptors (and thus drug targets) in living organisms. Currently, the major reason that new drugs fail to reach the clinic is lack of appropriate drug effect (approx. 30%). Thus, we need a better understanding of how GPCRs work and how this relates to disease. Our Program addresses this knowledge gap, using GPCR models that are relevant to treatment of metabolic, cardiovascular and central nervous system disease.
Control Of Cell Proliferation And Differentiation In Breast And Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$5,043,011.00
Summary
Breast and prostate cancer are the most commonly diagnosed cancers in women and men respectively, together accounting for >25% of all newly diagnosed cancers in Australia and other developed countries. Although significant improvements in the management of these cancers have occurred in the past 20 years further research is needed to better understand the molecular mechanisms of disease development and progression. Such research is critical to the better management and ultimate control of the ....Breast and prostate cancer are the most commonly diagnosed cancers in women and men respectively, together accounting for >25% of all newly diagnosed cancers in Australia and other developed countries. Although significant improvements in the management of these cancers have occurred in the past 20 years further research is needed to better understand the molecular mechanisms of disease development and progression. Such research is critical to the better management and ultimate control of these diseases through better treatments and prevention. A multidisciplinary team of cancer researchers at the Garvan Institute of Medical Research, with a 10 year track record of discovery and application of their research into breast and prostate cancer, will employ state-of-the-art research tools to identify new molecules and molecular pathways involved in these diseases. This new information will facilitate the improved management of these cancers through improved assessment of disease progression at the time of diagnosis and the development of new drugs and strategies for treatment and prevention.Read moreRead less
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 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
Colorectal Cancer - Molecular Basis To Targeted Therapeutics.
Funder
National Health and Medical Research Council
Funding Amount
$19,818,386.00
Summary
Cancer of the colon and rectum is the most common form of cancer in Australia. Over 12,000 people are diagnosed each year with colorectal cancer (CRC) and more than one third of people will die of their disease. CRC is caused by mistakes in production of colon cells. Our research aims to discover new ways to detect CRC, develop smart drugs and nanoparticle delivery systems for destroying all types of CRC cells. We will then test our new anti-cancer drugs in clinical trials with CRC patients.
Colon Cancer: Receptors, Signalling And Therapeutics
Funder
National Health and Medical Research Council
Funding Amount
$7,115,542.00
Summary
This program aims to understand the biochemical and biological basis of colorectal cancer, a major cause of cancer deaths in Australia. The Chief Investigators have extensive experience in the analysis of the molecular defects in colorectal cancer cells and have already developed new drugs to treat successfully experimental colon tumours in animals. During this research program, we will explore these systems further, concentrating on the identification of novel inhibitors of colon cancer cell gr ....This program aims to understand the biochemical and biological basis of colorectal cancer, a major cause of cancer deaths in Australia. The Chief Investigators have extensive experience in the analysis of the molecular defects in colorectal cancer cells and have already developed new drugs to treat successfully experimental colon tumours in animals. During this research program, we will explore these systems further, concentrating on the identification of novel inhibitors of colon cancer cell growth, survival and movement. Newly developed instruments and techniques will allow us to identify and detect the critical steps during the development of colorectal cancer and to design potent drugs to fight the disease. We have experience in conducting novel clinical trials in colon cancer and have developed imaging techniques for monitoring the effectiveness and safety of new anti-cancer drugs. Our collective scientific experience and ability to work in the clinic provides a unique opportunity for developing more effective treatments for colorectal cancer patients.Read moreRead less
This program brings together a team of researchers from The Walter and Eliza Hall Institute of Medical Research to study how the body regulates antibody production to fight disease. Antibodies are made by B-cells and are essential for a functional immune system. B cells circulate in the body, searching for signs of infection. When they encounter an invader, they mature, with the help of other immune cells, into antibody-producing cells. A small proportion of the cells are set aside as _memory� c ....This program brings together a team of researchers from The Walter and Eliza Hall Institute of Medical Research to study how the body regulates antibody production to fight disease. Antibodies are made by B-cells and are essential for a functional immune system. B cells circulate in the body, searching for signs of infection. When they encounter an invader, they mature, with the help of other immune cells, into antibody-producing cells. A small proportion of the cells are set aside as _memory� cells that can rapidly become antibodyproducing cells should the same infection occur again in the future. This is the basis of vaccination. This program aims to understand how a B cell changes into an antibody-producing cell, by studying the genes that are known to be required for the cells to form, or to do their work. We will study animals whose immune systems are under- or over-active, to find out what part of the antibody-producing process is faulty. Using this information, we hope eventually to be able to study diseases of antibody producing cells in humans (as occur in allergy, asthma, rheumatoid arthritis and leukaemia), to be able to identify the precise cause of the problem, and to suggest a therapy. This information may also be used to improve the outcome of vaccination where an enhanced antibody response is desired.Read moreRead less
Roles Of Impaired Apoptosis And Differentiation In Tumourigenesis And Therapy
Funder
National Health and Medical Research Council
Funding Amount
$21,656,910.00
Summary
The ten scientific laboratories in this program have joined forces to investigate two ways in which tumours develop. Both are of particular interest, because they suggest new ways in which cancer might be overcome. Most of our tissues are continually renewed throughout life by production of new cells. Therefore many of the old cells in each tissue must die off to maintain the proper cell numbers. To eliminate cells that are no longer needed or have become damaged, the body has developed a remark ....The ten scientific laboratories in this program have joined forces to investigate two ways in which tumours develop. Both are of particular interest, because they suggest new ways in which cancer might be overcome. Most of our tissues are continually renewed throughout life by production of new cells. Therefore many of the old cells in each tissue must die off to maintain the proper cell numbers. To eliminate cells that are no longer needed or have become damaged, the body has developed a remarkable cell suicide process termed apoptosis. Unfortunately, however, occasionally a random accident to the genes in one of our cells prevents the machinery for apoptosis from being turned on. In that case, the cell will not die when it should and, by continually dividing, it may eventually give rise to a cancer. Since most cancer cells still retain most of the machinery for apoptosis, however, a drug that could switch on this natural cell death machinery would provide a promising new approach to cancer therapy. Identifying and developing such drugs is one major long-term goal of this program. The other focus of our program concerns stem cells. These are rare cells with the remarkable ability to generate an entire tissue. For example, one of our laboratories has identified stem cells that can generate all the cells in the breast. The almost unlimited regenerative capacity of stem cells has a built-in danger. If a stem cell acquires the ability to proliferate excessively, it can go on to form a tumour. Indeed, many cancer researchers now suspect that rare stem cells within a tumour cause its inexorable growth. If tumour growth is maintained by stem cells, it will be essential to develop new forms of therapy that target these rare cancer stem cells rather than merely the bulk of the tumour cells. This is another key long-term goal of our program.Read moreRead less
Antigen Presentation, Recognition And The Immune Response
Funder
National Health and Medical Research Council
Funding Amount
$15,738,750.00
Summary
The early events in immunity require various molecular interactions. We will examine the structural and biophysical basis for some of these interactions, including those associated with transplant rejection and autoimmunity. We will explore the impact of variation in immune response genes on immune evasion and disease susceptibility. Our basic research will determine the mechanisms by which the immune system discriminates between different self and micro-organism associated determinants. We will ....The early events in immunity require various molecular interactions. We will examine the structural and biophysical basis for some of these interactions, including those associated with transplant rejection and autoimmunity. We will explore the impact of variation in immune response genes on immune evasion and disease susceptibility. Our basic research will determine the mechanisms by which the immune system discriminates between different self and micro-organism associated determinants. We will address the structural and biochemical basis for operation of an immune molecule called tapasin and unravel the basis for how some viruses escape the function of this molecule, thus allowing their immune evasion. We will also explore the use of modified small proteins called peptides in a humanized model of gluten hypersensitivity resembling that of Celiac disease. The molecular basis of the natural human immune system's capacity to recognise and reject grafts will be examined. This complements work aimed at improving the prediction of clinical graft rejection in transplantation. Dendritic cells play a central role in immunity, responsible for capturing material, whether from micro-organisms or self tissues, and presenting it to cells of the immune system. Our program will study the development and immunological function of the different dendritic cell subtypes. We will determine the relative contribution of each to the maintenance of immune tolerance and to the induction of immunity to several pathogens, including herpes simplex virus and malaria. Novel dendritic cell surface molecules that we have discovered will be tested for their ability to enhance the effectiveness of vaccines. Overall, this program utilises a broad array of immunological techniques designed to dissect the development and function of various immune system cell types and determine the structure-function relationships between important cell surface molecules involved in immunity.Read moreRead less