Regulation Of Intestinal Stem Cells And Intestinal Growth
Funder
National Health and Medical Research Council
Funding Amount
$419,018.00
Summary
How the small intestine grows is important for preterm babies and those with short bowel syndrome. This study investigates the mechanisms of growth in the normal situation and in animal model of short bowel syndrome. It investigates particular growth pathways that regulate growth and particularly that of intestinal stem cells.
Characterisation Of A Novel Prostate-expressed Kallikrein-like Protease And Its Target Proteins
Funder
National Health and Medical Research Council
Funding Amount
$724,544.00
Summary
Prostate disease is common in most men in later life and can affect their quality of life adversely. The primary conditions are benign prostatic hyperplasia or BPH and prostate cancer. Symptoms of BPH affect between 50-70% of men over the age of 50 and prostate cancer is now the most common internal cancer diagnosed in men. More importantly, prostate cancer is the second most common cause of cancer deaths. We don't yet fully understand exactly how these diseases occur but the male sex hormones o ....Prostate disease is common in most men in later life and can affect their quality of life adversely. The primary conditions are benign prostatic hyperplasia or BPH and prostate cancer. Symptoms of BPH affect between 50-70% of men over the age of 50 and prostate cancer is now the most common internal cancer diagnosed in men. More importantly, prostate cancer is the second most common cause of cancer deaths. We don't yet fully understand exactly how these diseases occur but the male sex hormones or androgens are known to play an important role. Prostate specific antigen or PSA has become widely accepted as a useful tool in helping to detect prostate cancer and then monitoring the disease. PSA, which is regulated by androgens, is an enzyme that either activates or breaks down many proteins that are important in both the normal function of the prostate and in the development of cancer. PSA belongs to a family of enzymes called the kallikreins. We have recently discovered a new member of this family that, like PSA, is also found in the prostate. We have called this new enzyme, K6, as it is the sixth member of this family to be identified. So , this project is about characterising this new K6 enzyme, finding out if it is also found in the prostates of men with BPH and prostate cancer, whether it is also regulated by androgens and what sort of proteins it may activate in these diseases. We will also compare these findings with what we know about PSA in these diseases. From these studies, we will not only understand more about this K6 enzyme and how it might be important in the prostate but also how it relates to PSA. These findings may ultimately lead to some new approaches in the detection and treatment for BPH and prostate cancer.Read moreRead less
Hyperplasia And Hypertrophy Of Airway Smooth Muscle In Asthma
Funder
National Health and Medical Research Council
Funding Amount
$286,250.00
Summary
Asthma is common in Australia with significant morbidity and it is the 6th Australian National Health Priority. Examination of the airways in asthma shows increased thickness of the airway wall (remodeling), and inflammation. Most long-term asthma treatment is currently focussed on treating inflammation. Since the contribution of smooth muscle to remodeling and excessive airway narrowing is crucial and may be largely independent of airway inflammation, new treatments aimed at the smooth muscle a ....Asthma is common in Australia with significant morbidity and it is the 6th Australian National Health Priority. Examination of the airways in asthma shows increased thickness of the airway wall (remodeling), and inflammation. Most long-term asthma treatment is currently focussed on treating inflammation. Since the contribution of smooth muscle to remodeling and excessive airway narrowing is crucial and may be largely independent of airway inflammation, new treatments aimed at the smooth muscle are needed. Treatments must be based on knowledge of the factors which result in more smooth muscle - hypertrophy (enlargement of cells), hyperplasia (more cells) or deposition of proteins (extracellular matrix) between the muscle cells. Matrix is produced by airway myofibroblasts which are more numerous in asthma. These various contributing factors have different signals that can be targeted for treatment, however, information regarding their relative importance is scant. We propose to examine cases of mild and severe asthma using archived tissue blocks in a multi-centre collaborative study using stereological techniques not previously applied to the airway in man. This study is important because it will: 1. Yield new data regarding the degree to which hyperplasia, hypertrophy and increased extracellular matrix vary in the airways; 2. Provide direction for the development of treatments of increased smooth muscle in asthma; 3. Provide relevance and direction to animal and tissue studies of airway smooth muscle; 4. Yield new information on the number of myofibroblasts in mild and severe asthma; 5. Yield new information on the effects of corticosteroids on smooth muscle, extracellular matrix and myofibroblasts in severe, fatal asthma, and 6. Relate increased smooth muscle to increased extracellular matrix, numbers of myofibroblasts and other airway wall dimensions including those close to the airway surface. These may be used to monitor airway pathology in asthma.Read moreRead less
A Randomised Controlled Trial Of High Dose Folic Acid To Slow The Progression Of Atheroma In Renal Failure (194246)
Funder
National Health and Medical Research Council
Funding Amount
$326,980.00
Summary
The Atherosclerosis and Folic Acid Supplementation Trial (ASFAST) is examining the effect of high dose folic acid supplementation on the development of desease of the heart and blood vessels in people with kidney failure. Subjects in the study take 15mg folic acid daily or a dummy tablet for 3 to 5 years. Folic acid is known to reduce the levels of a substance called homocysteine which is elevated in people with kidney disease. Homocysteine has been associated with disease of the heart and blood ....The Atherosclerosis and Folic Acid Supplementation Trial (ASFAST) is examining the effect of high dose folic acid supplementation on the development of desease of the heart and blood vessels in people with kidney failure. Subjects in the study take 15mg folic acid daily or a dummy tablet for 3 to 5 years. Folic acid is known to reduce the levels of a substance called homocysteine which is elevated in people with kidney disease. Homocysteine has been associated with disease of the heart and blood vessels and these diseases occur very commonly in people who also have kidney failure. I t is hoped that by using folic acid to reduce the levels of homocysteine, we can reduced the amounbt of heart and blood vessel disease in people with kidney failure.Read moreRead less
Novel Functional Domains On Adrenoceptors For Drug Interaction And Cell Signalling
Funder
National Health and Medical Research Council
Funding Amount
$801,500.00
Summary
Our work involves studying cell-surface proteins (receptors) that respond to hormones such as adrenaline or substances that transmit signals in the nervous system (neurotransmitters). These receptors play a vital role in orchestrating responses to stimuli such as stress, pain, changes in blood pressure, body temperature, fluid and energy status, and exercise. They allow communication between different organs or different parts of the nervous system. G-protein coupled receptors (GPCRs) are the ma ....Our work involves studying cell-surface proteins (receptors) that respond to hormones such as adrenaline or substances that transmit signals in the nervous system (neurotransmitters). These receptors play a vital role in orchestrating responses to stimuli such as stress, pain, changes in blood pressure, body temperature, fluid and energy status, and exercise. They allow communication between different organs or different parts of the nervous system. G-protein coupled receptors (GPCRs) are the major group of cell surface receptors that interact with hormones and neurotransmitters. Treatment of many diseases and conditions relies on the use of drugs that selectively activate or block a single type of GPCR. In fact, about 2-3 of existing therapies are based on these drugs. In designing new drugs it is important to understand as much as possible about the properties of the target receptors. There is emerging evidence concerning interactions between drugs, receptors and proteins inside cells that translate signals into responses (signalling proteins). For example, receptors have additional sites of drug action that can modulate their activity, and can also couple to multiple signalling pathways. We are studying adrenoceptors that respond to adrenaline and to the neurotransmitter noradrenaline. Our studies will use adrenoceptors as model systems to identify novel potential sites for drug interaction, to gain new insights into signalling mechanisms utilized by these receptors and to examine how a variety of phosphorylation mechanisms affect the ability of receptors to couple to particular signalling pathways.Read moreRead less
Androgen Receptor Mechanims In Female Reproductive Physiology
Funder
National Health and Medical Research Council
Funding Amount
$539,773.00
Summary
Infertility occurs in one in six Australian couples with 50% attributable to females, thus, enhancing our understanding of ovarian and uterine function is of great importance. This project tests the proposal that androgens (steroid hormones) play a major role in regulating female reproductive physiology through their interaction with the androgen receptor. We have developed novel mouse models which we will use to determine the roles of androgens in regulating female reproductive function.
Hormonal Modulation Of Prostatic Growth And Contractility
Funder
National Health and Medical Research Council
Funding Amount
$324,237.00
Summary
With increasing age human males are likely to develop benign prostatic hyperplasia (BPH), a disorder characterized by urethral obstruction due to an increase in size of the prostate gland. Drug treatments of this condition are not entirely satisfactory and the current project is to examine the mechanisms by which the prostate grows and occludes the urethra. We will use human prostate cells grown in artificial conditions to determine which hormones alter the types of cells and especially examine ....With increasing age human males are likely to develop benign prostatic hyperplasia (BPH), a disorder characterized by urethral obstruction due to an increase in size of the prostate gland. Drug treatments of this condition are not entirely satisfactory and the current project is to examine the mechanisms by which the prostate grows and occludes the urethra. We will use human prostate cells grown in artificial conditions to determine which hormones alter the types of cells and especially examine those cells which can contract as these may be of critical importance in the urethral obstruction. We hypothesize that an enzyme called protein kinase C may be implicitly involved in both cell growth and contractile function and we will examine the role of protein kinase C with a view ultimately to develop drugs which may interfere with this process and therefore aid in non-surgical treatment of the condition.Read moreRead less
Selectivity And Mode Of Action Of Rho-conopeptide TIA: A Novel Inhibitor Of Alpha1-adrenoceptors.
Funder
National Health and Medical Research Council
Funding Amount
$399,300.00
Summary
A major obstacle to the development of safer and more effective treatments for cardivascular diseases and benign prostatic hyperplasia is the inability to find small molecules with sufficient specificity to be safe and effective. The applicant team brings together a unique set of complementary research interests and skills in using conotoxins to define, at the molecular level, how rho-conotoxins act at the alpha1-adrenoceptor, a major drug target for cardiovascualr and related diseases. Rho-cono ....A major obstacle to the development of safer and more effective treatments for cardivascular diseases and benign prostatic hyperplasia is the inability to find small molecules with sufficient specificity to be safe and effective. The applicant team brings together a unique set of complementary research interests and skills in using conotoxins to define, at the molecular level, how rho-conotoxins act at the alpha1-adrenoceptor, a major drug target for cardiovascualr and related diseases. Rho-conotoxins are novel peptide inhibitors of the alpha1-adrenoceptor that appear to act at an undescribed allosteric site. This Project will use rho-conotoxins and analogues to characterise structurally and functionally how and where this class of conopepides act. The structure activity relationship for rho-conotoxins will be established to guide the development of subtype specific inhibitors. Pairwise interactins between the alpha1-adrenoceptorand TIA will be used to dock TIA onto a homolgy model of the alpha1-adrenoceptor. The long-term goal of the project is to develop new and safer treatments for cardiovascular and related disorders.Read moreRead less