Molecular Genetics Of Sex Determination And Gonad Development
Funder
National Health and Medical Research Council
Funding Amount
$4,580,898.00
Summary
Intersex disorders - ranging in severity from hypospadias (misplacement of the urethral opening) to complete sex reversal - are surprisingly common, with estimates as high as 4% of all live births. These disorders usually result in infertility, genital abnormalities, gender mis-assignment and long-term psychological trauma. The cause of these problems is most often the failure of the delicate network of gene regulation that is responsible for proper development of testes or ovaries in the embryo ....Intersex disorders - ranging in severity from hypospadias (misplacement of the urethral opening) to complete sex reversal - are surprisingly common, with estimates as high as 4% of all live births. These disorders usually result in infertility, genital abnormalities, gender mis-assignment and long-term psychological trauma. The cause of these problems is most often the failure of the delicate network of gene regulation that is responsible for proper development of testes or ovaries in the embryo. This research program will identify genes important for sex determination and development of the gonads, find out how these genes function and interact, and discover how they contribute to cases of aberrant sexual development in humans. Australia boasts three of the foremost international researchers in sex determination. Their contributions have been fundamental to the advancement of the field, including the identification and characterization of the master testis determining gene and other genes critical for sex determination. They now propose to pool their expertise in human molecular genetics, mouse developmental biology and protein chemistry to bring spectacular advances in our knowledge of human sexual development and its associated disorders. This information will be used to bring improved clinical care to patients withdisorders of sexual development.Read moreRead less
To study the genetic alterations that give rise to cancer. In particular, exploring how too little death of cells can lead to a tumour. If too few cells in a tissue die, a tumour may develop there. The team is exploring how the cell death process is normally controlled. They plan to characterise the molecules inside cells that determine whether a cell lives or dies and hope that better understanding of those molecules will help to explain how tumours arise. It could also lead to new drugs that c ....To study the genetic alterations that give rise to cancer. In particular, exploring how too little death of cells can lead to a tumour. If too few cells in a tissue die, a tumour may develop there. The team is exploring how the cell death process is normally controlled. They plan to characterise the molecules inside cells that determine whether a cell lives or dies and hope that better understanding of those molecules will help to explain how tumours arise. It could also lead to new drugs that can kill tumour cells more effectively by directly triggering the normal death switch of the cell.Read moreRead less
Many new therapies are being developed to treat stroke and prevent its recurrence. While a number of these have been successfully introduced, there is a puzzling gap between evidence of efficacy in animal models and humans. One of the main reasons may be lack of an integrated approach between the basic sciences and clinical researchers. By assembling a team with skills in both areas and a structure to maximise communication between groups this team plan to incrementally introduce new therapies i ....Many new therapies are being developed to treat stroke and prevent its recurrence. While a number of these have been successfully introduced, there is a puzzling gap between evidence of efficacy in animal models and humans. One of the main reasons may be lack of an integrated approach between the basic sciences and clinical researchers. By assembling a team with skills in both areas and a structure to maximise communication between groups this team plan to incrementally introduce new therapies into clinical practice.Read moreRead less
This program, run by an established team with skills in public health, clinical epidemiology, biostatistics, health economics and behavioural science addresses the under-researched issues of whether, when and how to use medical tests. The elements of the program follow the sequence in which testing is often done: for screening (early detection), for diagnosis on which to base treatment decisions, and for monitoring the effects of treatment. A common approach throughout is the identification of t ....This program, run by an established team with skills in public health, clinical epidemiology, biostatistics, health economics and behavioural science addresses the under-researched issues of whether, when and how to use medical tests. The elements of the program follow the sequence in which testing is often done: for screening (early detection), for diagnosis on which to base treatment decisions, and for monitoring the effects of treatment. A common approach throughout is the identification of the benefits and harms of testing and assessing their trade-off; how benefits weigh up against harms. This research is relevant to all partners in healthcare, (consumers, clinicians and policy-makers), who currently are being tested or using tests without being fully informed about the accuracy and effects of these tests.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
THE INTERFACE BETWEEN INNATE AND ADAPTIVE IMMUNITY
Funder
National Health and Medical Research Council
Funding Amount
$4,905,420.00
Summary
Allergic disorders including asthma are amongst the most prevalent diseases in Australia afflicting up to 25% of the population and costing the Australian Government in excess of $600 million annually. This program aims to understand the molecular and cellular mechanisms controlling airway inflammation, focusing on the cross-talk between scavenger cells at airway surfaces and circulating cells of the immune system. These studies will combine sophisticated mouse models of airway inflammation in t ....Allergic disorders including asthma are amongst the most prevalent diseases in Australia afflicting up to 25% of the population and costing the Australian Government in excess of $600 million annually. This program aims to understand the molecular and cellular mechanisms controlling airway inflammation, focusing on the cross-talk between scavenger cells at airway surfaces and circulating cells of the immune system. These studies will combine sophisticated mouse models of airway inflammation in the laboratory with clinical investigation and analysis of human tissue. Understanding these processes will translate into better treatments for patients suffering from life-threatening allergy and asthma.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
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
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