Application of novel exact combinatorial optimisation techniques and metaheuristic methods for problems in cancer research. Novel biotechnologies are offering an unprecedented opportunity to understand the genetic basis of cancer development and progression. However, they present us with a challenge; new computational methods and improved mathematical models and algorithms need to be introduced to complement these technologies in the determination of the function of our individual genetic makeup ....Application of novel exact combinatorial optimisation techniques and metaheuristic methods for problems in cancer research. Novel biotechnologies are offering an unprecedented opportunity to understand the genetic basis of cancer development and progression. However, they present us with a challenge; new computational methods and improved mathematical models and algorithms need to be introduced to complement these technologies in the determination of the function of our individual genetic makeup, especially in connection with disease states. The project will deal with research questions and datasets related to some of the highest incidence cancers in Australia. This project will contribute towards the development of new powerful algorithms for pattern recognition for future "personalized" molecular diagnostics methods.Read moreRead less
Communicating genetic information in families: practical, legal, social and ethical issues. The outcomes of this study, will give evidence as to whether or not people do pass on genetic risk information to relatives, how they do it, what the barriers are, what their preferences are. It will also provide data so that mechanisms for best practice communication and clear guidelines for legal and health professionals can be developed. Effective communication and exchange of genetic risk information ....Communicating genetic information in families: practical, legal, social and ethical issues. The outcomes of this study, will give evidence as to whether or not people do pass on genetic risk information to relatives, how they do it, what the barriers are, what their preferences are. It will also provide data so that mechanisms for best practice communication and clear guidelines for legal and health professionals can be developed. Effective communication and exchange of genetic risk information will benefit individual health and the health of future generations.Read moreRead less
The Genetic Study Of Diabetic Retinopathy Risk In Type 1 Diabetes Mellitus
Funder
National Health and Medical Research Council
Funding Amount
$32,628.00
Summary
Type 1 diabetes is a disorder leading to high blood sugars, which can damage the small blood vessels of the the back of the eye and potentially lead to blindness. However not all diabetics will develop blinding eye disease. Our project aims to find the genes that contribute to the development of blinding diabetic eye disease so that patients who carry the genes can be managed and treated appropriately. This will help to reduce the incidence of blindness related to diabetic eye disease.
Analysis Of The Role Of Polycomb Genes In Normal And Diseased Breast Stem Cells
Funder
National Health and Medical Research Council
Funding Amount
$362,810.00
Summary
In Australia, 1 in 8 women will be diagnosed with breast cancer. Many will receive chemotherapy that will apparently eliminate the cancer. However, in approximately 1 in 3 of these women, cancer will recur. This is thought to be due to the presence of chemotherapy-resistant breast cancer stem cells. This project will study the parallels between the role of Polycomb genes in normal mammary stem cell maintenance and their role in breast cancer, in order to improve treatment and cure rates.
Characterization Of A Novel Human X-linked Gene RBMX, A Candidate For X-linked Mental Retardation
Funder
National Health and Medical Research Council
Funding Amount
$356,870.00
Summary
We recently discovered a novel gene (which we have called RBMX for RNA-binding protein, X chromosome) on the human X chromosome. Its function is quite unknown, but it is active in all tissues, and it has changed very little in evolution, so we think it must have an important function in human development. Genes with a similar sequence bind to RNA and convert it to its final active form, so RBMX may have a similar role. Other RNA-binding proteins are active in the brain, so we suspect that RBMX m ....We recently discovered a novel gene (which we have called RBMX for RNA-binding protein, X chromosome) on the human X chromosome. Its function is quite unknown, but it is active in all tissues, and it has changed very little in evolution, so we think it must have an important function in human development. Genes with a similar sequence bind to RNA and convert it to its final active form, so RBMX may have a similar role. Other RNA-binding proteins are active in the brain, so we suspect that RBMX may be involved in brain development and learning. The RBMX gene is also interesting because it has a copy called RBMY on the human Y chromosome, which is thought to have a critical (unknown) function in sperm production. Of particular note is our finding that RBMX maps to the long arm of the human X chromosome at Xq26. This is a region that contains several inherited mental retardation syndromes called X linked mental retardation (XLMR) which are carried by females and manifest in males. At least eight XLMR syndromes have been mapped to human Xq26. Several of the syndromes have characteristic skeletal and facial abnormalities, as well as a range of other anomalies.. We will completely characterise the human RBMX gene. As well as giving us fresh clues to its function, this will allow us to make a mouse strain that lacks the gene (knockout) so we can see whether it is critical for life, and if it is involved in brain development and learning. Identification of an XLMR gene coding for an RNA binding protein will shed light on the role of RNA metabolism in the brain, and the effect of disruptions of RNA processing on mental function. We will then screen the RBMX gene in families with XLMR syndromes, to look for RBMX mutations in patients which may cause XLMR. If mutations in RBMX cause one or more XMLR phenotypes, it will be possible to use this knowledge to diagnose the condition and detect carriers.Read moreRead less
Functional Evaluation Of BRCA1 & BRCA2 Unclassified Sequence Variants And Identification Of Critical Pathogenic Domains.
Funder
National Health and Medical Research Council
Funding Amount
$331,312.00
Summary
The major genes that predispose to hereditary breast cancer are called BRCA1 and BRCA2. Most mutations in these genes cause the protein product to be truncated and inactive. However there are many families in which such truncating mutations are not found, but instead there are sequence changes that slightly alter the protein product. It is often difficult to predict whether these sequence variants are likely to cause hereditary breast cancer simply by looking at the position and nature of the se ....The major genes that predispose to hereditary breast cancer are called BRCA1 and BRCA2. Most mutations in these genes cause the protein product to be truncated and inactive. However there are many families in which such truncating mutations are not found, but instead there are sequence changes that slightly alter the protein product. It is often difficult to predict whether these sequence variants are likely to cause hereditary breast cancer simply by looking at the position and nature of the sequence change. Consequently, it is not possible to offer informative genetic counselling to these women or their at-risk family members. Assessment of the potential pathogenicity and functional significance of these unclassified sequence variants will be directly useful with regard to the clinical management of these women and their families, and will develop our current understanding of how different domains of these genes contribute to their role as cancer susceptibility genes.Read moreRead less
The Identification Of Novel Genes Involved In The Initiation And Development Of Thyroid Neoplasia
Funder
National Health and Medical Research Council
Funding Amount
$227,545.00
Summary
Thyroid cancer is the most frequently diagnosed endocrine malignancy, comprising 1% of all human malignancy. However, its actual occurrence indicated by autopsy studies may be as high as 10%. To date, a number of genes, both oncogenes (genes that are inappropriately switched on and take part in the process of tumour development) and tumour suppressor genes (genes that are switched off and lose their protective role against tumour development), have been implicated in the development of thyroid c ....Thyroid cancer is the most frequently diagnosed endocrine malignancy, comprising 1% of all human malignancy. However, its actual occurrence indicated by autopsy studies may be as high as 10%. To date, a number of genes, both oncogenes (genes that are inappropriately switched on and take part in the process of tumour development) and tumour suppressor genes (genes that are switched off and lose their protective role against tumour development), have been implicated in the development of thyroid cancer. However mutations, mistakes in the genetic code, of these genes account for only a small percentage of thyroid tumours and none of these genes have been shown to be useful as clear prognostic markers for tumour progression or aggressiveness. The merging of the 2 fields of cytogenetics (the study of chromosomes) and molecular genetics (the study of genes at the DNA and RNA level) has strengthened our ability to understand the process of tumour development. We are proposing use of a technique called Comparative Genomic Hybridisation to aid in the identification of new genes associated with tumour development in both benign and malignant thyroid disease. This technique has already been used to aid in the location of genes with a role in ovarian and brain cancer and in some familial syndromes characterised by breast and gastrointestinal malignancies. This method involves the detection of regions of chromosomal amplifications or deletions in tumour DNA that is fluorescently labelled (green), mixed with normal human DNA also fluorescently labelled (red). If the tumour contains regions of amplification (likely housing an oncogene), analyses show increased green fluorescence and if deletions are present (likely housing a tumour suppressor gene), analyses show increased red fluorescence. Chromosomal regions identified by this method will be further analysed to identify the precise genes they contain and establish a role for these genes in the development of thyroid tumours.Read moreRead less
Molecular Genetic Characterisation Of A Novel X-linked Skeletal Myopathy
Funder
National Health and Medical Research Council
Funding Amount
$158,104.00
Summary
This project aims to identify the genetic basis of a new disease that is characterised by episodes of muscular weakness. This disease only affects males. The signficance of the project is that this is the first description of such a disorder and gives us an opportunity to study a previously unsuspected aspect of human muscle function.
Novel bioinformatics approaches for biological inference from comparative genomics data. Unlocking the potential of the human and other genome sequences depends almost entirely upon comparative genomics techniques. We will develop powerful bioinformatic models, implemented as high-performance computing solutions, for the examination of gene sequences. Improving these models, which represent the initial building block for all comparative genomics techniques, will be beneficial across genomics dep ....Novel bioinformatics approaches for biological inference from comparative genomics data. Unlocking the potential of the human and other genome sequences depends almost entirely upon comparative genomics techniques. We will develop powerful bioinformatic models, implemented as high-performance computing solutions, for the examination of gene sequences. Improving these models, which represent the initial building block for all comparative genomics techniques, will be beneficial across genomics dependent industries. A major outcome from this work will be an integrated software/hardware product optimised for statistical examination of very large-scale genomics data.Read moreRead less
Using Next-generation Sequencing Technology To Explore The Genetic Basis Of Human Disease
Funder
National Health and Medical Research Council
Funding Amount
$278,463.00
Summary
This project will use powerful new DNA sequencing technologies to analyse the genes that underlie common diseases such as diabetes, arthritis and cancer in a large and diverse set of human DNA samples, and to find mutations in Australian patients suffering from rare genetic muscle disorders. This approach will provide novel information about the evolutionary origins and genetic basis of common disease and identify new genes that cause inherited muscle diseases.