Molecular Mechanisms For The Cell-type Specific Regulation Of The Tissue-type Plasminogen Activator Gene
Funder
National Health and Medical Research Council
Funding Amount
$490,500.00
Summary
Tissue-type plasminogen activator (t-PA) is an important enzyme that is widely known for its ability to remove blood clots. More recently, t-PA has been shown to influence memory development and under pathological conditions can promote neuronal cell death. t-PA is produced by many cells including the endothelial cells that line the blood vessels, fibroblasts, as well as cells within the central nervous system. The t-PA gene is regulated very differently in these cell types and this project will ....Tissue-type plasminogen activator (t-PA) is an important enzyme that is widely known for its ability to remove blood clots. More recently, t-PA has been shown to influence memory development and under pathological conditions can promote neuronal cell death. t-PA is produced by many cells including the endothelial cells that line the blood vessels, fibroblasts, as well as cells within the central nervous system. The t-PA gene is regulated very differently in these cell types and this project will address the mechanisms underlying the cell-type specific regulation of the t-PA gene. Endothelial cells, fibroblasts and neuronal cell cultures will be used to study the regulation of t-PA expression. Information gained will not only add to the understanding of the broader field of gene regulation, but may also provide clues to manipulate the expression of the t-PA gene in different cells.Read moreRead less
Epigenomic Marks As Indicators Of The Kinetics Of Gene Activation In Immune Cells.
Funder
National Health and Medical Research Council
Funding Amount
$619,805.00
Summary
Switching on an immune response involves major changes in the gene expression program of the immune cells. These changes in gene expression take place in the context of DNA packaged into the nucleus in a structure known as chromatin. We will investigate the relationship between chromatin and gene expression changes and how this relationship plays a role in the timing of the immune response. This information will be useful in developing novel means of controlling aberrant immune responses.
Genomic Characterisation Of Asbestos Related Lung Cancer
Funder
National Health and Medical Research Council
Funding Amount
$88,099.00
Summary
Lung cancer causes more deaths in Australia than any other cancer. Smoking is the main cause, but people exposed to asbestos are also at risk, and it can be difficult to know whether a case is due to tobacco, asbestos or both. We will study lung cancer genes in people with asbestos exposure to find whether asbestos lung cancer has a specific pattern of abnormal genes (signature). If so, this could help people entitled to compensation, and also point to new treatments for asbestos lung cancer
Investigating The Role Of MtrA In Antimicrobial Resistance Of N. Gonorrhoeae
Funder
National Health and Medical Research Council
Funding Amount
$329,023.00
Summary
The main aim of this project is to investigate how genes are regulated by a specific protein called MtrA. This protein has been involved in antibiotic resistance in Neisseria gonorrhoeae, and has recently been shown to be important for the survival of N. gonorrhoeae in early infections. Understanding the exact mechanisms of this resistance, and how the genes regulated by MtrA are important for early N. gonorrhoeae infections would aid in treatment options.
Retrotransposon Regulation Of The Human Innate Immune Response
Funder
National Health and Medical Research Council
Funding Amount
$231,937.00
Summary
Complete sequencing of the human genome has revealed the positions of approximately 20,000 genes. In addition, nearly 50% of the human genome is comprised of repetitive sequences previously thought of as junk DNA. Numerous studies are now finding that this DNA actually has a variety of important functions, particularly in the control of gene activity. This project will examine the relationships between gene expression and nearby repetitive sequences during the innate immune response in humans.
The Role Of Ikaros In Establishing Regulatory Networks For Lymphocyte Development
Funder
National Health and Medical Research Council
Funding Amount
$345,809.00
Summary
Ikaros is a protein that regulates gene expression during development of lymphocytes from blood stem cells. Ikaros has a profound importance in normal and malignant lymphocyte development, but we still do not know how it controls these processes. The aim of my study is to identify genes regulated by Ikaros and the molecular mechanisms of their regulation. This study will contribute to understanding of the regulatory network controlling the development and function of lymphocytes.
Inferring Global Regulatory Architecture Of Human Gene Expression In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$47,427.00
Summary
Our genome encodes ~25,000 genes that shape out an individual from head to toe. Malfunction of a particular gene could cause fatal health problem or disease. Nonetheless, the mis-regulation of functioning genes can also result in serious diseases. In this study, we are going to use large-scale gene regulation information and advanced computing techniques to clarify the regulation network of human genome on a global level. Hence, helping us to understand more about diseases of gene transcription.
Retrotransposons As Controlling Elements In Mammals: A Screen For Expression In Somatic Cells And Cancer
Funder
National Health and Medical Research Council
Funding Amount
$452,545.00
Summary
Differences between individual mammals are generally thought to be due to differences either between their genes, or between their environments. However, in many cases genetic or environmental factors cannot account for differences between individuals. We have studied mice in which dramatic differences between genetically identical individuals are due solely to the activity of a type of transposable element (transposon). There are tens of thousands of similar elements in the genomes of all mamma ....Differences between individual mammals are generally thought to be due to differences either between their genes, or between their environments. However, in many cases genetic or environmental factors cannot account for differences between individuals. We have studied mice in which dramatic differences between genetically identical individuals are due solely to the activity of a type of transposable element (transposon). There are tens of thousands of similar elements in the genomes of all mammals. A large body of evidence demonstrates that transposons can disrupt gene expression. To prevent this from occurring, most organisms have evolved mechanisms to keep transposons silent. However, fragmentary evidence indicates that transposons are at least sometimes expressed in normal and cancer cells. We hypothesize that activity of transposons in mammals alters gene expression sufficiently to cause variation between individuals, and that altered gene expression can cause disease (particularly cancer) and some manifestations of aging. As a first step toward testing this hypothesis, it is essential to acquire more complete information on the expression of transposons in normal and diseased cells. Furthermore, if transposon expression is closely linked to the development or progression of cancer or aging, then the ability to monitor such expression could have diagnostic utility. DNA array technology is coming into wide use to compare patterns of gene expression in different types of cells. We propose to adapt this method to the study of transposon expression. We will clone examples of all known classes of mouse and human transposon, and study transposon expression in: 1. Normal mice, at intervals from the earliest phase of development to old age, and 2. Human cancers of a variety of types. These studies will provide information of fundamental significance for mammalian biology, and also have the potential to lead to improved diagnosis of disease.Read moreRead less
In Vivo And In Vitro Studies Of The Human -308 TNF Promoter Polymorphism.
Funder
National Health and Medical Research Council
Funding Amount
$232,131.00
Summary
The identification of genetic variation in region of the DNA that controls expression of the inflammatory cytokine Tumour Necrosis Factor (TNF) and its association with a number of autoimmune and inflammatory diseases, has led to speculation that this genetic difference may play a role in predisposing some people to these diseases. We have isolated an activity, TPF1, that may regulate expression through interaction with this DNA control region. During the tenure of this grant we intend to clarif ....The identification of genetic variation in region of the DNA that controls expression of the inflammatory cytokine Tumour Necrosis Factor (TNF) and its association with a number of autoimmune and inflammatory diseases, has led to speculation that this genetic difference may play a role in predisposing some people to these diseases. We have isolated an activity, TPF1, that may regulate expression through interaction with this DNA control region. During the tenure of this grant we intend to clarify some of these questions, we will generate genetically modified mice that have either of the two genetic forms of the human TNF promoter. These mice will be compared in two models of associated disease, murine Lupus and cerebral malaria. We will also characterise the interactions of TPF1 with other components of the TNF control region. An understanding of the role of TPF1 in controlling TNF expression and an appreciation of the cell types that are able to express the phenotype, will allow the development of more subtle, cell specific strategies to modulate the activity of TNF without completely abolishing expression and may lead to better preventative and therapeutic strategies.Read moreRead less