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High-Throughput Screening Of The Genome And Proteome In Postmortem CNS From Subjects With Schizophrenia
Funder
National Health and Medical Research Council
Funding Amount
$553,190.00
Summary
Schizophrenia is a serious psychiatric illness that effects ~1% of the Australia population. The underlying pathology of the illness remains unknown. This application seeks funding to use new technologies to screen approximately 60% of the expressed human genome and proteome to determine which genes are being differentially expressed in two regions thought to be important in generating the symptoms of the illness, the frontal cortex and hippocampus. This project will generate a large amount of d ....Schizophrenia is a serious psychiatric illness that effects ~1% of the Australia population. The underlying pathology of the illness remains unknown. This application seeks funding to use new technologies to screen approximately 60% of the expressed human genome and proteome to determine which genes are being differentially expressed in two regions thought to be important in generating the symptoms of the illness, the frontal cortex and hippocampus. This project will generate a large amount of data, however by comparing the data from subjects with schizophrenia to that from control subjects and subjects with bipolar disorder who were psychotic and being treated with antipsychotic drugs close to death will allow us to identify changes that are specific to schizophrenia. Genes that are expressing different levels of mRNA and protein will become prime targets for future investigations as they are likely to be central to the pathology of the illness.Read moreRead less
Identification Of Genes Involved In Neural Crest Development
Funder
National Health and Medical Research Council
Funding Amount
$482,310.00
Summary
Knowledge of the genes that during embryonic development control the way our bodies form is necessary to understanding how our body systems function in health and disease. However, research on the developmental genetics of vertebrates, including humans, has proceeded very indirectly, mostly by looking for genes similar to those found in other biological systems, most notably the fruit fly. The significance of this research is that it will identify developmental genes directly from the chosen ver ....Knowledge of the genes that during embryonic development control the way our bodies form is necessary to understanding how our body systems function in health and disease. However, research on the developmental genetics of vertebrates, including humans, has proceeded very indirectly, mostly by looking for genes similar to those found in other biological systems, most notably the fruit fly. The significance of this research is that it will identify developmental genes directly from the chosen vertebrate body system as it develops. As a body system we will choose one of the most basic building blocks of the very early nervous system. This building block is an embryonic organ called the Neural Crest that later goes on to form important parts of the nervous system, but in addition it also forms major parts of the head and face, glands in the neck, the large arteries leading out from the heart, and pigment cells (melanocytes) in the skin. It is particularly important to gain insight into development of this organ because the tissues that derive from the neural crest are the most at risk for birth defects and for childhood cancers. Knowledge of neural crest development also tells us about our own evolution, because the neural crest is the only major system found only in vertebrates including humans.Read moreRead less
Functional Analysis Of Candidate Sex-determining And Gonadal Development Genes
Funder
National Health and Medical Research Council
Funding Amount
$503,500.00
Summary
This project is aimed at finding and studying the genes that control whether an embryo develops as a male or a female, and the genes that are responsible for proper development of the gonads, organs that control an individual's sexual development. It is thought that a genetic chain of events is important for gonadal development, and we aim to find the missing links of that chain and to work out how they fit together, as well as how genetic defects can lead to disorders of sexual development. Def ....This project is aimed at finding and studying the genes that control whether an embryo develops as a male or a female, and the genes that are responsible for proper development of the gonads, organs that control an individual's sexual development. It is thought that a genetic chain of events is important for gonadal development, and we aim to find the missing links of that chain and to work out how they fit together, as well as how genetic defects can lead to disorders of sexual development. Defects in sexual development in the human embryo not only result in some of the most common forms of birth defects but also have profound physiological and psychosexual ramifications for the afflicted individuals. A fuller understanding of the causes of these defects will lead to improved patient management.Read moreRead less
The Function Of An Essential Histone Variant During Early Development.
Funder
National Health and Medical Research Council
Funding Amount
$436,980.00
Summary
Gene expression in a cell occurs in the nucleus where genes are stored. In the nucleus, DNA is not in a free form but is covered with an equivalent weight of protein to form a structure known as chromatin. Chromatin is a periodic structure made up of repeating, regularly spaced subunits, the subunit being the nucleosome. A nucleosome consists of a group of proteins (histones) wrapped around with DNA. A nucleosome is capable of blocking gene expression therefore one important function of chromati ....Gene expression in a cell occurs in the nucleus where genes are stored. In the nucleus, DNA is not in a free form but is covered with an equivalent weight of protein to form a structure known as chromatin. Chromatin is a periodic structure made up of repeating, regularly spaced subunits, the subunit being the nucleosome. A nucleosome consists of a group of proteins (histones) wrapped around with DNA. A nucleosome is capable of blocking gene expression therefore one important function of chromatin is to prevent unwanted gene expression which is essential to allow an organism to develop properly. When gene expression is not accurately controlled by chromatin developmental defects or cancer could result from the production of incorrect proteins. To control correct gene expression, highly specific mechanisms must operate in the cell to remove, or disrupt, nucleosomes at certain genes at a precise time during development. One mechanism that we believe to be important is changing the make-up of a nucleosome. This can be achieved in the cell by the replacement of histones with different specialised forms of these histones (variants). It is thought that these histone variants could specifically expose certain genes and thereby turn them on. Once the correct protein is made in sufficient amounts the histone variants could be rapidly exchanged for the normal histones to shut off the gene. Employing a new approach, we will study one of these histone variants to discover the role it plays in turning genes on at precise times in early development during the formation of different specialised cell types. This new information may define targets for the prevention of incorrect gene expression during cancer progression or abnormal development.Read moreRead less
Characterisation Of Candidate Colorectal Cancer Genes Identified By Microarray And SSH Analysis
Funder
National Health and Medical Research Council
Funding Amount
$417,750.00
Summary
Bowel cancer is one of the leading causes of cancer death in Australia today. If diagnosed early, surgery cures most patients. Unfortunately, symptoms often are not present until the cancer is advanced. In these cases surgery is still performed but sometimes all the cancer cannot be removed or it comes back after surgery. We need better ways to identify patients in whom the cancer is likely to return and better chemotherapy drugs to treat cancer not able to be removed surgically. Recently it has ....Bowel cancer is one of the leading causes of cancer death in Australia today. If diagnosed early, surgery cures most patients. Unfortunately, symptoms often are not present until the cancer is advanced. In these cases surgery is still performed but sometimes all the cancer cannot be removed or it comes back after surgery. We need better ways to identify patients in whom the cancer is likely to return and better chemotherapy drugs to treat cancer not able to be removed surgically. Recently it has been recognised that there are different subgroups of bowel cancer. One of these subgroups contains changes in the DNA called microsatellite instability, MSI-H for short. MSI-H cancers are less likely to come back after surgical removal and there is some evidence that they respond differently to chemotherapy. All cancers develop due to changes in their genetic material which make the cancer cells behave more aggressively than normal cells. We think that MSI-H bowel cancers have different changes in their genetic material compared to non-MSI-H bowel cancers. Understanding what these differences are would allow a better understanding of why bowel cancers do or do not come back after surgery. It would also allow chemotherapy treatments to be individualised according to genetic changes in the cancer. We have already used DNA chip technology to identify a large number of genetic differences between MSI-H and non-MSI-H bowel cancers. In this project we want to examine the most important of these in more detail. We will replicate these changes in cells cultured in the laboratory to see if the changes really do affect the behaviour of cancer cells. We will then look for what kind of genetic damage has led to the change. For key genetic changes, we will then examine our large tumour bank of bowel cancers collected with patients' consent over many years. We will look to see if the genetic changes really do predict the cancers' behaviour and response to treatment.Read moreRead less
MICRORNA PREDICTORS OF OESOPHAGEAL TUMOUR RESPONSE TO CHEMOTHERAPY AND RADIOTHERAPY
Funder
National Health and Medical Research Council
Funding Amount
$659,990.00
Summary
Chemoradiotherapy (CRT) is used for the treatment of oesophageal cancer before surgical resection, and for patients not undergoing surgery. However, it is unsuccessful for many, causing side effects, no clinical gain, and delaying surgery. MicroRNAs are small molecules that control cellular functions. This project will identify miRNA markers which are able to predict cancer response to CRT, and this will help clinical decision making for individualized treatment.
Chondrocyte Hypertrophy In Development And Disease
Funder
National Health and Medical Research Council
Funding Amount
$360,018.00
Summary
Whereas chondrocyte hypertrophy is a normal feature of skeletal growth, in adult chondrocytes it is associated with osteoarthritis (OA). We propose that collagen II fragments provide signals for hypertrophy in cartilage. The lack of collagen II fragments in our collagenase-resistant mouse provides a unique opportunity to address the role of collagen II fragments in driving cellular hypertrophy. We will identify bioactive collagen II fragments that represent novel targets for OA therapies
Motor Functioning In Autism And Asperger's Disorder: Furthering Current Neurobehavioural And Clinical Definitions
Funder
National Health and Medical Research Council
Funding Amount
$354,932.00
Summary
While it is well known that autism and Asperger's disorder are associated with social, communicative, and behavioural symptoms, it is less well known that affected individuals also have considerable movement and coordination difficulties. For example, these children often have problems with hand writing, walking, hopping, skipping, catching, and running. These skills are very important for success at school; for example, if children are unable to participate in school sports they often feel isol ....While it is well known that autism and Asperger's disorder are associated with social, communicative, and behavioural symptoms, it is less well known that affected individuals also have considerable movement and coordination difficulties. For example, these children often have problems with hand writing, walking, hopping, skipping, catching, and running. These skills are very important for success at school; for example, if children are unable to participate in school sports they often feel isolated and rejected from the peer group. Also, hand writing problems have a significant impact on children's academic performance. Our previous research has suggested that there may be particular patterns of motor problems that characterise individuals with autism and Asperger's disorder. Our proposed research aims to use the kinds of 3D motion analysis technology used in the movie industry to capture exactly how people affected by these conditions move and respond to the environment. This study will enable us to highlight particular parts of the brain-motor circuitry that are affected by these disorders and will also enable us to more clearly distinguish how autism is different from Asperger's disorder. Ultimately, it is hoped that our motor investigations will lead to improved assessment and interventions for these disorders.Read moreRead less