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Populations of viruses in an host can be very diverse and just as the behaviour of a population of humans can be very different to the behaviour of individuals in them, populations of viruses behave differently to the behaviour of individuals in them. This diversity may provide a survival advantage to the virus and it also may regulate the severity of the symptoms in an infected host. This study will provide important new information that will drive vaccine strategies and public health policy.
Biological And Mathematical Studies Of Development Of The Enteric Nervous System
Funder
National Health and Medical Research Council
Funding Amount
$390,250.00
Summary
During very early development in the embryo, cells migrate from the future brain. These cells, called neural crest cells, make there way to the nearest part of the gut, in the future oesophagus. They then migrate as a growing population right along the gut until they have populated the entire gut down to the rectum. To complicate matters, the gut itself is rapidly growing length-wise as this migration occurs. These neural crest cells then form the nerve cells that reside in the gut and which con ....During very early development in the embryo, cells migrate from the future brain. These cells, called neural crest cells, make there way to the nearest part of the gut, in the future oesophagus. They then migrate as a growing population right along the gut until they have populated the entire gut down to the rectum. To complicate matters, the gut itself is rapidly growing length-wise as this migration occurs. These neural crest cells then form the nerve cells that reside in the gut and which control gut function. In a common birth defect, Hirschsprung's disease, this migration stops short of the rectum so that the last part of the gut never develops nerve cells. This region lacking nerve cells is unable to propel the gut contents and, if untreated, this condition of intractable constipation is fatal after birth. Eight genes, when mutated, give essentially the same condition either in humans or animals, but the link between the genes and the condition is still not clear. We have proposed that the genes code for molecules that effect the way the neural crest cells interact with other neural crest cells and with the cells of the gut in which migration takes place. The link between the genes and the development of a normal gut nerve system (or its failure, as in Hirschsprung's disease) operates at the level of the dynamics of the neural crest cell population, interacting with the dynamics of gut growth. This project will use very detailed biological data acquisition to feed into newly formulated original mathematical models to tease out the important links between the neural crest cell population and the growing gut, that control cell migration. This will lead to an understanding of formation of the gut nerve system and of Hirschsprung's disease, at the population level, a level not well served by molecular levels of understanding. These models will have application in the many developmental contexts where cell movement and growth are simultaneous.Read moreRead less
Population Dynamics Of Tissue-specific Effector And Regulatory CD4+ T Cells
Funder
National Health and Medical Research Council
Funding Amount
$394,250.00
Summary
Survival of white blood cells in the body is an active process and is important for the maintainence of a T cell population which can recognise a wide variety of foreign antigens. At present the fate of T lymphocytes which recognise self antigens is unclear. Knowledge of the survival kinetics of self-reactive T lymphocytes and the mechanism by which they are regulated in the normal individual is crucial to be able to control the development of various diseases, including autoimmune diseases. Fro ....Survival of white blood cells in the body is an active process and is important for the maintainence of a T cell population which can recognise a wide variety of foreign antigens. At present the fate of T lymphocytes which recognise self antigens is unclear. Knowledge of the survival kinetics of self-reactive T lymphocytes and the mechanism by which they are regulated in the normal individual is crucial to be able to control the development of various diseases, including autoimmune diseases. From our previous studies of autoimmune gastritis we have generated cell lines of lymphocytes that recognise stomach-specific antigens and with these unique reagents we will perform experiments to determine the fate of these self-reactive T cells in a normal individual. Also we will determine the impact of different amounts of the tissue antigens on the survival and activation of self-reactive T cells, and finally how a special class of lymphocytes, know as regulatory lymphocytes, act in vivo to control the activity of self-reactive T cells. We will use not only classical immunological approaches to address these issues but also state of the art imaging, to visualise the nature of the cell interactions in living tissues. The information arising from this work will underpin strategies to selectively turn off self-reactive lymphocytes that cause disease, will form the basis of clinical development of cell based therapies to treat autoimmune diseases, and the imaging technologies developed in this grant will have wide applicability to the study of a range of immune responses.Read moreRead less
Post-market Surveillance Of Medicine-related Adverse Events
Funder
National Health and Medical Research Council
Funding Amount
$99,248.00
Summary
Observational studies using administrative data are an important complement to spontaneous reporting systems for detecting medicine-related adverse events after they go to market, as they reflect real-world use of medicines; yet, they require rigorous methodological approaches to avoid bias. This project will review the existing methodologies for detecting adverse events in administrative data and apply them to Australian data.
Mitochondrial Damage Following Fetal Hypoxia Or Birth Asphyxia: Using Creatine To Preserve Mitochondrial Function
Funder
National Health and Medical Research Council
Funding Amount
$838,726.00
Summary
There is a need for a therapy that can be given before a mother gives birth to protect the baby should ‘oxygen starvation’ threaten the baby’s brain and other organs such as the heart, kidney, lungs, and the ability to breathe properly. We are suggesting that an increased intake of creatine is a very effective treatment against this threat, and its proven safety and ease of use recommends it for wide application, particularly in countries where the access to medical resources is poor.
Biobank Networks, Medical Research And The Challenge Of Globalisation
Funder
National Health and Medical Research Council
Funding Amount
$790,698.00
Summary
Medical research increasingly relies on large-scale biobanks that store tissue samples from healthy donors or patients. Over the past decade, international networks of biobanks have been established. These are scientifically valuable but raise numerous legal and ethical challenges. In this project we will generate evidence to inform the development of ethically rigorous strategies to ensure that Australian donors and biobanks contribute to, and benefit from, international biobank networks.
Investigation Of Early Cell Surface Rearrangements Mediating Adequate TCR-pMHC Engagement
Funder
National Health and Medical Research Council
Funding Amount
$303,708.00
Summary
This project aims to use advanced cell imaging techniques to view precise interactions that occur between cells as our immune system attacks and destroys infected cells. The techniques to be employed are highly advanced and involve cutting edge science. Essentially these techniques allow the production of movies of the body's immune system in action. Determining these interactions in such detail is important for understanding the body’s ability to fight infection.
Gene Discovery And Functional Studies To Reveal Mechanisms Underlying Mitochondrial Respiratory Chain Disorders.
Funder
National Health and Medical Research Council
Funding Amount
$381,343.00
Summary
Mitochondrial respiratory chain disorders are a devastating group of disorders, potentially affecting any organ of the body, with no effective therapies currently available. The majority of these disorders have a childhood onset and the genetic basis for most of them is unknown. Identification of the genes responsible for these disorders in specific families would greatly improve the accuracy and usefulness of genetic counselling, and an understanding of their biology may assist the development ....Mitochondrial respiratory chain disorders are a devastating group of disorders, potentially affecting any organ of the body, with no effective therapies currently available. The majority of these disorders have a childhood onset and the genetic basis for most of them is unknown. Identification of the genes responsible for these disorders in specific families would greatly improve the accuracy and usefulness of genetic counselling, and an understanding of their biology may assist the development of effective therapies.Read moreRead less