Infectious Large Capacity Vectors For Gene Therapy
Funder
National Health and Medical Research Council
Funding Amount
$374,625.00
Summary
The next 25 to 50 years will witness the culmination of a demographic shift in the age of the population which will be associated with an increasing importance of both inherited predispositions to late-onset chronic, complex diseases and natural degenerative processes. Medicine has historically sought to manage and cure the symptoms of disease. The focus for therapy has begun to switch from alleviating the ailments to establishing and resolving their causes. On the back of the Human Genome Proje ....The next 25 to 50 years will witness the culmination of a demographic shift in the age of the population which will be associated with an increasing importance of both inherited predispositions to late-onset chronic, complex diseases and natural degenerative processes. Medicine has historically sought to manage and cure the symptoms of disease. The focus for therapy has begun to switch from alleviating the ailments to establishing and resolving their causes. On the back of the Human Genome Project, genetics research will identify genes that are central to these processes, leading to gene-based medicine. Some of this new treatment will be drug-based but an alternative is the correction of the defective genes themselves gene therapy to either replace inherited faulty genes or to provide novel or modified genes that may help the repair and maintenance of tissue, or combat abnormal processes such as cancer. Gene therapy is a field still in its infancy with just a few qualified successes reported in the past few years. Persistent expression of a transgene at therapeutic levels is required for successful gene therapy. Most of the currently used vector and virus systems have a small capacity and usually employ a reduced (cDNA) copy of the transgene lacking natural control mechanisms. These are prone to vector loss and promiscuous expression or loss of expression. The delivery of genomic DNA up to 20 times this size would enable genes to be transferred in entirety, including their natural regulatory elements. This project aims to develop a vector system based on Herpesviruses that tackles some of the problems with the current generation of gene therapy vectors. This system is particularly aimed at providing long-term gene expresssion at physiological levels and safe, efficient delivery systems through the use of genomic DNA.Read moreRead less
Further Characterisation Of The Role Of HSSB1 In DNA Repair And Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$85,526.00
Summary
To date, all breast cancer predisposition genes identified play an important role in the DNA damage repair pathway. We have characterised a new protein designated as hSSB1, which plays a crucial role in the maintenance of genomic stability by protecting us from DNA damage. Significantly, evidence strongly suggests an interaction of hSSB1 with the breast cancer susceptibility protein BRCA2. This project will investigate the role of hSSB1 in breast cancer predisposition and DNA damage repair.
Defining Biomarkers Of Colorectal Cancer Prevention By Dietary Agents And Translation To Human Intervention Studies
Funder
National Health and Medical Research Council
Funding Amount
$632,924.00
Summary
This research will explore dietary agents for their ability to regulate the damage to DNA that is responsible for causing bowel cancer. The plan is to identify a dietary approach that will effectively reduce the risk of colon cancer. The science will be tested in animal models followed by initial human experiments aimed at testing the relevance to humans.
Epigenetic Inheritance Through Meiosis At The Agouti Locus In Mice
Funder
National Health and Medical Research Council
Funding Amount
$182,699.00
Summary
The manifestations of many genetic traits do not conform to the rules of Mendelian inheritance. In humans, some alleles give a completely predictable phenotype, while others display a wide range of phenotypes, described as differences in penetrance and expressivity. As the phenotype associated with a particular gene in humans may be modified by the genotype at unlinked modifying loci and by environmental factors, it is difficult to determine to what extent any single factor is responsible for va ....The manifestations of many genetic traits do not conform to the rules of Mendelian inheritance. In humans, some alleles give a completely predictable phenotype, while others display a wide range of phenotypes, described as differences in penetrance and expressivity. As the phenotype associated with a particular gene in humans may be modified by the genotype at unlinked modifying loci and by environmental factors, it is difficult to determine to what extent any single factor is responsible for variability. In mice, however, a number of examples of variable expressivity have been reported in conditions where genetic background and environment have been controlled. For example, the phenotypes of mice with mutations at the agouti locus can vary substantially between genotypically identical littermates. Epigenetic modifications such as DNA methylation are known to be involved. Furthermore, the phenotypes of the offspring are related to the phenotype of the mother and recent experiments carried out in our laboratory suggest that this is the result of inheritance of the epigenetic state of the allele through the female germline. This is the first report of epigenetic inheritance at an endogenous gene in mammals. The experiments described in this project should help to clarify the mechanisms involved in variable expressivity and epigenetic inheritance. Variable expressivity in combination with epigenetic inheritance may be viewed as an alternative method of inheritance of genetic traits which does not involve DNA mutation, but which can be carried from generation to generation in a semipermanent way. Understanding the mechanisms underlying these phenomena is a challenge for contemporary genetics.Read moreRead less
Role Of DNA Methylation And Non-coding RNA In Human Centromere Function
Funder
National Health and Medical Research Council
Funding Amount
$499,000.00
Summary
A chromosome is a grouping of coiled strands of DNA, containing many genes. Every human cell has 23 pairs of chromosomes, which together comprise the genome. Both gain and loss of any of these chromosomes will lead to severe medical problems including birth defects and cancer development. Thus, the understanding of the mechanisms underlying the exact passage of these chromosomes from a parental cell to two new cells during cell division, and how the information is copied from from one cell gener ....A chromosome is a grouping of coiled strands of DNA, containing many genes. Every human cell has 23 pairs of chromosomes, which together comprise the genome. Both gain and loss of any of these chromosomes will lead to severe medical problems including birth defects and cancer development. Thus, the understanding of the mechanisms underlying the exact passage of these chromosomes from a parental cell to two new cells during cell division, and how the information is copied from from one cell generation to another, is an important area of research, however, much remains to be learnt about the mechanisms. Our laboratory was the first to discover a key component of the chromosome that is involved in the regulation of the cell division process, ensuring the accurate segregation of chromosomes. This structure, known as a neocentromere, is an ideal model system to study important aspects of chromosome segregation. The present project proposes to study the properties of this neocentromere in detail. The outcome will contribute to our knowledge on the processes underlying cell and chromosome division, which will ultimately have a direct impact on our understanding of the causes for some of the most common clinical conditions that affect human health.Read moreRead less