Production Of Humanised Mouse Models For Haemoglobin E And 0-thalassaemia
Funder
National Health and Medical Research Council
Funding Amount
$280,693.00
Summary
The proposed study aims to identify and characterise genes critical to male fertility using two mouse models of infertility: 1) Joey mouse line: an ENU induced model of sperm abnormalities. Following linkage analysis, candidate genes will be selected for sequencing to identify the causal mutation. 2) Ggn knockout mice. The role of the testis-specific gene, Ggn will be characterised through a phenotypic analysis of Ggn knockout mice and a series of expression and biochemical analyses. Both models ....The proposed study aims to identify and characterise genes critical to male fertility using two mouse models of infertility: 1) Joey mouse line: an ENU induced model of sperm abnormalities. Following linkage analysis, candidate genes will be selected for sequencing to identify the causal mutation. 2) Ggn knockout mice. The role of the testis-specific gene, Ggn will be characterised through a phenotypic analysis of Ggn knockout mice and a series of expression and biochemical analyses. Both models will be of direct value in the identification of commercially relevant contraceptive targets, as well as furthering our understanding of male reproductive function.Read moreRead less
A Novel Molecular Target Capable Of Abrogating Neuroblastoma Development
Funder
National Health and Medical Research Council
Funding Amount
$802,499.00
Summary
Although modern chemotherapy has significantly improved survival rates for many childhood cancers, the outlook remains dismal for children with advanced staged neuroblastoma. These patients frequently have alterations in the cancer-causing gene called MYCN. Using pre-clinical models of MYCN-driven neuroblastoma and genome sequencing we have discovered a gene that can completely block the action of MYCN and prevent neuroblastoma growth. This work will characterize the function of this novel gene.
Identifying Novel Antimalarial Targets Using ENU Mutagenesis In The Mouse
Funder
National Health and Medical Research Council
Funding Amount
$760,170.00
Summary
Malaria is estimated to cause 1.2 million deaths per year. The malarial parasite has developed resistance to most drugs and new drugs are needed. We aim to mimic the protective red blood cell diseases common in human populations in malarial endemic areas by identifying host targets that are important in parasite growth.
Identifying Target Genes For Novel Anti-epileptic Therapies In The Mouse
Funder
National Health and Medical Research Council
Funding Amount
$469,802.00
Summary
Epilepsy is a disease which affects 2-4% of the population. There are a wide range of drugs available to treat the condition but there is consistently 30-40% of patients who do not respond well to any of these drugs and who continue to have seizures. The reason that there are no drugs available for these people is that most of the drugs available have been designed along the same principles. A new set of principles is needed to develop new drugs which will be able to treat those people not respo ....Epilepsy is a disease which affects 2-4% of the population. There are a wide range of drugs available to treat the condition but there is consistently 30-40% of patients who do not respond well to any of these drugs and who continue to have seizures. The reason that there are no drugs available for these people is that most of the drugs available have been designed along the same principles. A new set of principles is needed to develop new drugs which will be able to treat those people not responding to current therapy. This project is designed to identify new biologic pathways which may be interrupted with drugs to prevent seizures in people with epilepsy. This project uses a procedure to induce mutations into genes in mice and then screens for mice which do not seize when challenged with a drug which generates seizures in mice. Genetic studies will identify the mutated genes and these will be used as potential targets for new therapies or will identify new biological pathway which should expand the use of future anti-epileptic drugs.Read moreRead less
Translational Study Of The Genetics Of Systemic Autoimmunity Based On Mouse Mutagenesis
Funder
National Health and Medical Research Council
Funding Amount
$518,500.00
Summary
Lupus is the prototypic autoimmune disease. It is characterised by inflammation that can damage virtually any organ in the body. This inflammation is the outcome of a complex interplay between the environment and genetic predisposition, resulting in production of antibodies against components of normal tissue. Better characterisation of the genetic basis of lupus is a priority because it is the single best path towards a clearer understanding of the mechanism of this debilitating disease, and ul ....Lupus is the prototypic autoimmune disease. It is characterised by inflammation that can damage virtually any organ in the body. This inflammation is the outcome of a complex interplay between the environment and genetic predisposition, resulting in production of antibodies against components of normal tissue. Better characterisation of the genetic basis of lupus is a priority because it is the single best path towards a clearer understanding of the mechanism of this debilitating disease, and ultimately, new therapeutic options. Strategies used to identify the genetic basis of human disease fall into two categories. The first involves gathering genetic information from families with more than one affected member, which is then compared with genetic information from unaffected people. This can identify genetic regions likely to contain disease-causing genes, but so far, this approach has met with limited success in lupus. Although regions of the genome that harbour disease-associated genes have been found, few actual disease causing genes have been confirmed. The second approach begins with known genes that might plausibly cause the disease, based on prior knowledge then tests are performed to see whether particular variants of these genes are more common in patients than in healthy controls. Obviously this approach is usually biased towards investigation of candidate genes that are already well-characterised. In this project, we will combine information obtained from a large-scale mouse-based programme in which genetic changes that cause features of lupus are generated randomly. In other words, there is an unbiased search for candidate genes, which should lead to the discovery of new disease pathways. Since the mouse and human immune systems are remarkably similar, genetic abnormalities that cause features of lupus in mice are highly likely to be informative about the genetic basis of human lupus, a hypothesis we will test with genetic studies in humans with lupus.Read moreRead less
Functional Analysis Of A Novel Genetic Mouse Model For Congenital Growth Hormone Deficiency
Funder
National Health and Medical Research Council
Funding Amount
$519,131.00
Summary
Pituitary Hormone deficiency is not uncommon and is associated with poor growth, metabolism and fertility. Some cases of this disorder arise due to genetic changes that compromise the ability of the pituitary gland to make or secrete growth hormone (GH). Using cutting-edge genomics technology, we have generated a new genetic mouse model of GH deficiency. The aim of this project is to understand the function of this novel GH _regulating gene in mice and in humans.
Role Of Inflammation In The Physiological And Pathological Function Of The Gastrointestinal Tract
Funder
National Health and Medical Research Council
Funding Amount
$443,946.00
Summary
The gastrointestinal tract is continuously exposed to the external environment as a consequence of what we ingest. We have therefore evolved distinct mechanisms to deal with exposure to non-pathogenic insults in the gut. Sometimes, however these mechanisms fail leading to chronic inflammation and resultant pathology, which can under certain circumstances develop into cancer. This study will investigate inflammation in the gut, with particular interest in the systems that control inflammation.
ENU Mutagenesis To Identify Targets For Host-directed Therapy Against Malaria.
Funder
National Health and Medical Research Council
Funding Amount
$660,175.00
Summary
Malaria kills up to one million people annually, mainly children and pregnant women. The drugs that are used to treat malaria are becoming useless due to the malarial parasite developing resistance to these drugs. We are looking at a totally new way of developing drugs that target molecules in humans , depriving the parasites of crucial factors. By using this approach, the malaria parasite will be unable to develop resistance to these new drugs and millions of lives may be saved.