Use Of The Norfolk Island Genetic Isolate For Disease Gene Mapping
Funder
National Health and Medical Research Council
Funding Amount
$978,500.00
Summary
This gene mapping study will use a unique founder effect population to investigate two major public health disorders. We aim to identify genes that play a role in migraine and in cardiovascular disease, using a population from Norfolk Island. The Norfolk Island community is a population of ~1200 permanent residents, the majority of whom are direct descendents of 18th century English Bounty mutineers and Polynesian women. We will undertake a full genome scan to identify migraine gene loci and QTL ....This gene mapping study will use a unique founder effect population to investigate two major public health disorders. We aim to identify genes that play a role in migraine and in cardiovascular disease, using a population from Norfolk Island. The Norfolk Island community is a population of ~1200 permanent residents, the majority of whom are direct descendents of 18th century English Bounty mutineers and Polynesian women. We will undertake a full genome scan to identify migraine gene loci and QTL that influence cardiovascular disease using samples from this population isolate.Read moreRead less
Statistical Methods And Algorithms For Analysis Of High-throughput Genetics And Genomics Platforms
Funder
National Health and Medical Research Council
Funding Amount
$1,557,500.00
Summary
Through rapid advances in high-throughput -omics technologies, the number of phenotypes and the number of genotypes in gene mapping studies are or will be orders of magnitudes larger than in previous studies. Current algorithms and analysis methods have not kept up with the speed of data collection, nor has the training of qualified researchers. We will develop quantitative trait loci (fine) mapping analysis methods and bioinformatics algorithms and train (post)graduates in these research areas.
Functional Characterization Of The Regulatory Architecture Of Melanoma-associated Loci
Funder
National Health and Medical Research Council
Funding Amount
$645,663.00
Summary
Melanoma accounts for more than 75% of skin cancer related deaths. In Australia, >10,000 new cases are diagnosed yearly. In this proposal, we will apply novel genetic sequencing technologies developed in our laboratory to examine genomic regions that are associated with melanoma development. By focusing on selected areas, we will obtain a much deeper understanding of how these genes are regulated and find new ways of detecting and treating this disease.
Importance Of Histone Variant H2AZ Acetylation In Gene Activation In Cancer
Funder
National Health and Medical Research Council
Funding Amount
$611,737.00
Summary
DNA is packaged in the cell in such a way that essential genes are available to be switched on by the transcription machinery. The packaging involves nucleosomes, that consist of four histone proteins, H2A, H2B, H3 and H4. H2A.Z is a histone variant that is often over expressed in cancer, and therefore could lead to abnormal gene transcription. This project is focused on understanding the role of H2A.Z in gene deregulation in cancer as modification of this mark may provide a potential novel canc ....DNA is packaged in the cell in such a way that essential genes are available to be switched on by the transcription machinery. The packaging involves nucleosomes, that consist of four histone proteins, H2A, H2B, H3 and H4. H2A.Z is a histone variant that is often over expressed in cancer, and therefore could lead to abnormal gene transcription. This project is focused on understanding the role of H2A.Z in gene deregulation in cancer as modification of this mark may provide a potential novel cancer therapeutic target.Read moreRead less
Understanding The Role Of Chromosome Condensation Proteins And Their Link To Disease
Funder
National Health and Medical Research Council
Funding Amount
$601,224.00
Summary
Cells divide through a complex cascade of signals from our genetic material (DNA) which need to be finely tuned for events to occur properly. Errors in control cause faulty cell division and lead to diseases such as cancer. We have identified a master controller of these events termed the condensin complex and aim to understand how it orchestrates these functions by creating a map of its DNA location and understanding which regions in the genetic material it controls and how.
Clinical Classification Of Regulatory Variants In Breast Cancer Susceptibility Genes
Funder
National Health and Medical Research Council
Funding Amount
$536,966.00
Summary
Variations in our genes can confer a risk of diseases including breast cancer. Determining the clinical significance of these variations is a major and increasing challenge for genetic counselors and clinicians. This project will evaluate the clinical significance of variants in the control regions of breast cancer susceptibility genes. This research will inform the development of guidelines for interpreting such variants in a clinical setting.
Understanding The Regulation Of The Location Of Chromosomes Within The Nucleus
Funder
National Health and Medical Research Council
Funding Amount
$333,612.00
Summary
The nucleus of each human cell, despite being under 10µM in diameter, contains 46 chromosomes, each consisting of several centimeters of DNA. The organisation of chromosomes within the nucleus helps regulate which genes are switched on and off. Genes attached to the nuclear lamina, which lines the nuclear membrane, tend to be switched off. Mutations in the nuclear lamina cause several diseases, including progeria, resulting premature aging. I am interested in understanding why only certain regio ....The nucleus of each human cell, despite being under 10µM in diameter, contains 46 chromosomes, each consisting of several centimeters of DNA. The organisation of chromosomes within the nucleus helps regulate which genes are switched on and off. Genes attached to the nuclear lamina, which lines the nuclear membrane, tend to be switched off. Mutations in the nuclear lamina cause several diseases, including progeria, resulting premature aging. I am interested in understanding why only certain regions of the genome attach to the nuclear lamina.Read moreRead less
Molecular Insights Into Long Noncoding RNA-protein Complexes: Important Gene Regulators In Cancer
Funder
National Health and Medical Research Council
Funding Amount
$388,927.00
Summary
Cancer cells turn good genes off and bad ones on: but how do they do this? Recent breakthroughs suggest that noncoding RNA, produced from so-called ‘junk’ DNA, is important. One such noncoding RNA forms paraspeckles, a novel component of the cell machinery. Here, we will pick apart the way paraspeckles are organised and function, to develop them as a prototype for designing anti-cancer treatments against noncoding RNAs.
Nuclear Retention-and-release Of RNA: A Naturally-occurring Mechanism For Controlling Gene Expression
Funder
National Health and Medical Research Council
Funding Amount
$428,753.00
Summary
The deliberate retention of messenger RNA in the nucleus is a newly-discovered biological mechanism used by cells to control which genes are made into proteins, and when. This is a fundamental process in health and disease. The project will employ cutting edge molecular and cellular techniques to discover the principles underpinning nuclear retention. These insights will allow the development of new methods to spatially and temporally control gene expression in diverse gene therapy applications.