Transcriptome Profiling Of The Human Pathogen Schistosoma Japonicum
Funder
National Health and Medical Research Council
Funding Amount
$257,560.00
Summary
The parasitic disease, schistosomiasis, caused by human bloodflukes of the genus Schistosoma, is a major public health issue in Africa, Latin America and South East Asia. Current control methods are far from ideal, and a comprehensive understanding of the genetic mechanisms which allow schistosomes to grow, develop and survive within their hosts affords the best prospect for identifying new drug and vaccine targets. Microarray technology allows simultaneous monitoring of thousands of different g ....The parasitic disease, schistosomiasis, caused by human bloodflukes of the genus Schistosoma, is a major public health issue in Africa, Latin America and South East Asia. Current control methods are far from ideal, and a comprehensive understanding of the genetic mechanisms which allow schistosomes to grow, develop and survive within their hosts affords the best prospect for identifying new drug and vaccine targets. Microarray technology allows simultaneous monitoring of thousands of different genes, and to determine where and when they are active, thus placing the mass of data generated by genome sequencing programs into a biological and functional context. Microarrays provide a unique, cutting-edge, tool for investigating schistosome biology. We have fabricated a microarray representing some 20,000 schistosome genes. We will use this resource to perform large scale monitoring of schistosome gene expression during the parasite's complex life cycle, targetting the regionally important Asian schistosome, Schistosoma japonicum, for study. This will provide the single largest insight into the genetic changes that occur during schistosome development, will greatly further our understanding of the adaptations needed for the growth, development and survival of the parasite, and will identify genes involved in key biological processes, all of which may be exploitable for future interventions and treatments.Read moreRead less
Primary central nervous system (CNS) tumours, arising in the brain and spinal cord, are the leading cause of cancer-related deaths in children less than 15 years of age. Medulloblastomas and other primitive neuroectodermal tumours (PNETs) are the most common form of primary childhood brain tumours, accounting for 25-30% of cases. Despite notable recent advances in our understanding of the molecular genetic basis of malignancies, the pathogenesis of CNS PNETs remains obscure. To address this prob ....Primary central nervous system (CNS) tumours, arising in the brain and spinal cord, are the leading cause of cancer-related deaths in children less than 15 years of age. Medulloblastomas and other primitive neuroectodermal tumours (PNETs) are the most common form of primary childhood brain tumours, accounting for 25-30% of cases. Despite notable recent advances in our understanding of the molecular genetic basis of malignancies, the pathogenesis of CNS PNETs remains obscure. To address this problem, we propose to apply a novel combinatorial approach for the identification of PNET tumour suppressor genes utilising both representational difference analysis (RDA) and microarray expression profiling. Data from this study will help to elucidate the molecular pathways that are compromised in the initiation and growth of PNETs. This information will have direct implications for the development of improved diagnostic and prognostic indicators necessary for the design of more effective therapeutic strategies for the treatment of PNET patients.Read moreRead less
Array-based Comparative Genomic Hybridisation In Lung Cancer
Funder
National Health and Medical Research Council
Funding Amount
$314,773.00
Summary
Lung cancer is the most frequent cause of cancer deaths in many Western countries, including ours. Lung cancer is the third leading cause of death of Australians and the fifth leading cause of burden of disease in Australia. In many cases, even with the best treatment available, the lung cancer spreads from where it starts, to other parts of the lung, chest and throughout the body. This eventually leads to death. We are interested in the factors that influence when and how lung cancer spreads. W ....Lung cancer is the most frequent cause of cancer deaths in many Western countries, including ours. Lung cancer is the third leading cause of death of Australians and the fifth leading cause of burden of disease in Australia. In many cases, even with the best treatment available, the lung cancer spreads from where it starts, to other parts of the lung, chest and throughout the body. This eventually leads to death. We are interested in the factors that influence when and how lung cancer spreads. With exposure to cancer-causing agents such as cigarette smoke, parts of the lung may suffer permanent damage that increases the risk of lung cancer. Many of these changes include the genes in air passages and lung tissue. In this study, we will use the latest technology in genetics called gene chips to study changes in genes that affect the spread of lung cancer. These gene chips can study a vast number of genes at once. In particular, we will whether there is an abnormal number of copies of genes in the lung cancer. We hope that this research study will provide new information about the diagnosis and treatment of lung cancer.Read moreRead less
Genomic Profiling To Predict Lung Cancer Metastases
Funder
National Health and Medical Research Council
Funding Amount
$323,500.00
Summary
Lung cancer is the most frequent cause of cancer deaths in many Western countries, including ours. Lung cancer is the third leading cause of death of Australians and the fifth leading cause of burden of disease in Australia. In many cases, even with the best treatment available, the lung cancer spreads from where it starts, to other parts of the lung, chest and throughout the body. This eventually leads to death. We are interested in the factors that influence when and how lung cancer spreads. W ....Lung cancer is the most frequent cause of cancer deaths in many Western countries, including ours. Lung cancer is the third leading cause of death of Australians and the fifth leading cause of burden of disease in Australia. In many cases, even with the best treatment available, the lung cancer spreads from where it starts, to other parts of the lung, chest and throughout the body. This eventually leads to death. We are interested in the factors that influence when and how lung cancer spreads. With exposure to cancer-causing agents such as cigarette smoke, parts of the lung may suffer permanent damage that increases the risk of lung cancer. Many of these changes include the genes in air passages and lung tissue. In this study, we will use the latest technology in genetics called gene chips to study changes in genes that affect the spread of lung cancer. These gene chips can study a vast number of genes at once. We hope that this research study will provide new information about the diagnosis and treatment of lung cancer.Read moreRead less
Genetic And Biochemical Analysis Of The PIM/LAM Biosynthetic Pathway In Mycobacteria.
Funder
National Health and Medical Research Council
Funding Amount
$272,250.00
Summary
Tuberculosis (TB) is one of the most devastating diseases in human history. TB kills approximately two millions people each year worldwide, more than any other disease caused by a single infectious agent. The disease has re-emerged in recent years due to the AIDS epidemic and the appearance of TB bacteria that are not killed by currently available antibiotics. New antibiotics must be developed to combat this global health threat. This requires the identification of targets on the bacteria on whi ....Tuberculosis (TB) is one of the most devastating diseases in human history. TB kills approximately two millions people each year worldwide, more than any other disease caused by a single infectious agent. The disease has re-emerged in recent years due to the AIDS epidemic and the appearance of TB bacteria that are not killed by currently available antibiotics. New antibiotics must be developed to combat this global health threat. This requires the identification of targets on the bacteria on which antibiotics can act. One particularly attractive target is the outer coat of the bacterium. Several existing antibiotics target the bacterial coat, yet the ways in which coat is assembled are poorly understood. Two related compounds in the bacterial coat, and unique to TB bacteria, are called PIMs and LAMs. The structures of these compounds are known, and the compounds appear to be essential for the survival of the bacteria in the human host. However, the mechanisms by which PIMs and LAMs are made by the bacteria are very poorly understood. The aim of our research proposal is to better understand the process by which these compounds are made. If this process can be blocked by an antibiotic, then this represents a potential anti-TB therapy which could save millions of lives worldwide.Read moreRead less
The properties of Vegf-B suggest that it may play a role in new blood vessel formation (angiogenesis) especially during the development of the heart. Mice with the Vegf-b gene deleted are viable and fertile but display cardiac dysfunction as the animals age and in experimental conditions of ischemia. Comparison of total gene expression in the hearts of mice lacking Vegf-B with those of normal mice will identify genes involved in blood vessel formation during cardiac development and maintenance. ....The properties of Vegf-B suggest that it may play a role in new blood vessel formation (angiogenesis) especially during the development of the heart. Mice with the Vegf-b gene deleted are viable and fertile but display cardiac dysfunction as the animals age and in experimental conditions of ischemia. Comparison of total gene expression in the hearts of mice lacking Vegf-B with those of normal mice will identify genes involved in blood vessel formation during cardiac development and maintenance. The genes identified will be targets for designing potential new drugs and therapies for cardiovascular disease.Read moreRead less
Use Of Expression Profiling To Identify Genes Influencing Cardiovascular Risk In The Norfolk Island Population Isolate
Funder
National Health and Medical Research Council
Funding Amount
$697,409.00
Summary
This study will use a unique population isolate from Norfolk Island. We aim to identify genes that play a role in cardiovascular disease risk. Norfolk has a population of ~1200 permanent residents, most of whom are direct descendents of 18th century English Bounty mutineers and Polynesian women. We will undertake gene expression mapping to identify genomic loci that influence cardiovascular disease using samples from this population isolate.
Role Of MicroRNAs In The Control Of MRNA Translation
Funder
National Health and Medical Research Council
Funding Amount
$360,500.00
Summary
This project studies the function of a recently discovered class of ribonucleic acid (RNA) molecules termed microRNAs (miRNAs). They appear to have very important functions in all multicellular organisms, since many of them have undergone little change over hundreds of millions of years. At present we know that miRNAs probably work by regulating the efficiency with which messenger RNAs (mRNAs) are translated into protein molecules. However we do not know how they accomplish this, or which mRNAs ....This project studies the function of a recently discovered class of ribonucleic acid (RNA) molecules termed microRNAs (miRNAs). They appear to have very important functions in all multicellular organisms, since many of them have undergone little change over hundreds of millions of years. At present we know that miRNAs probably work by regulating the efficiency with which messenger RNAs (mRNAs) are translated into protein molecules. However we do not know how they accomplish this, or which mRNAs are regulated by miRNAs. Our work to date has suggested to us that miRNAs may act in combination with one another on mRNAs, so that the effect on a given mRNA depends on just which miRNAs are present, and how abundant they are. We propose to construct a system in which the function of miRNAs can be studied in vitro, using crude cell extracts that are known to perform mRNA translation and related functions. This will, for the first time, make it possible to test miRNAs in carefully controlled conditions, and ask which steps in translation they affect. We will be able to investigate just how the pairing of miRNA and mRNA sequences determines the ability of a miRNA to act on a specific mRNA, and to confirm that a given miRNA actually does regulate a specific mRNA. To facilitate this goal, we will use three methods to isolate mRNAs that are targets of miRNA regulation. Each of these methods relies on the physical interaction of miRNA and mRNAs in cell extracts. In one method, we will attach a tag to a miRNA, and use the tag to pull out associated mRNAs. In another method, we will use an antibody to a protein that is thought to associate with all miRNAs. The antibody should pull out any mRNAs associated with the miRNA-protein complex. Finally, we will identify mRNAs that have responded to the presence of a miRNA by changing the efficiency with which they are translated. These experiments will provide essential knowledge about an extremely important biological system.Read moreRead less
Novel Molecules Underlying The Development Of Corticopetal And Corticofugal Pathways
Funder
National Health and Medical Research Council
Funding Amount
$289,250.00
Summary
The mammalian brain consists of many discrete areas which perform specific functions. Each area has specific sets of connections with other brain areas. These sets of connections underlie the ability of the brain to execute functions critical to our daily lives, such as sight, hearing, touch and movement, as well as more complex functions such as memory, motivation and reasoning. We currently know little about how the sets of connections which underlie these functions are formed. The aim of this ....The mammalian brain consists of many discrete areas which perform specific functions. Each area has specific sets of connections with other brain areas. These sets of connections underlie the ability of the brain to execute functions critical to our daily lives, such as sight, hearing, touch and movement, as well as more complex functions such as memory, motivation and reasoning. We currently know little about how the sets of connections which underlie these functions are formed. The aim of this project is to understand how some of the connections between the cortex and other brain areas are formed during development. To do this the project will combine modern molecular techniques with neuroanatomy to identify molecules that are expressed by specific populations of neurons during critical developmental stages. These molecules will then be misexpressed in order to determine whether they are important for the development of appropriate connectivity in the brain. A knowledge of the molecules that regulate the development of neuronal pathways is critical to understanding brain development. In the long term, it will also lead to the development of therapies for cases when the brain is damaged or does not develop appropriately due to disease or injury.Read moreRead less
Integrated Analysis And Functional Characterisation Of Gene Amplicons In Ovarian Cancer
Funder
National Health and Medical Research Council
Funding Amount
$453,068.00
Summary
In Australia in 2001 there were ~1300 new cases of ovarian cancer. Survival of ovarian cancer is very poor and current treatments inadequate. To develop more effective treatments we need to understand the molecular events that cause ovarian cancer. Some genes have multiple copies in ovarian cancer cells and these may be good targets for therapy. We aim to find these genes and determine which ones have a functional effect in the tumour.