Identification Of Genes For X-linked Mental Retardation.
Funder
National Health and Medical Research Council
Funding Amount
$675,228.00
Summary
We propose to identify novel heritable causes of intellectual disability using 22 large and well-characterised families from Australia. In these families we have refined the location of the genetic defect to the chromosome X and excluded the contribution of all so far known genes. We will achieve this using the technology of massive parallel sequencing. At the completion of the project we will have identified novel causes of intellectual disability and devised tests to identify them.
Investigating The Role Of The UPF3B Gene And Nonsense Mediated RNA Decay (NMD) Process In Mental Retardation.
Funder
National Health and Medical Research Council
Funding Amount
$572,710.00
Summary
Intellectual disability is a frequent and important medical problem. Genetic and environmental factors contribute about equally to the aetiology of intellectual disability. Estimated 1-3% of population suffer from a form of intellectual disability. Among the genetic factors contributing to intellectual disability are genes, and their mutations, on one of the human chromosomes, chromosome X. We have been studying human X-chromosome genes for many years and discovered in excess of 20 novel genes c ....Intellectual disability is a frequent and important medical problem. Genetic and environmental factors contribute about equally to the aetiology of intellectual disability. Estimated 1-3% of population suffer from a form of intellectual disability. Among the genetic factors contributing to intellectual disability are genes, and their mutations, on one of the human chromosomes, chromosome X. We have been studying human X-chromosome genes for many years and discovered in excess of 20 novel genes causing various forms of intellectual disability. Surprisingly the number of genes, in which mutations cause various forms of intellectual disability is unexpectedly high. Just on the human X-chromosome we expect in excess of 200 such genes, which is nearly 30% of the gene content of this chromosome. We propose to study a novel gene, UPF3B, we recently identified to be mutated in a form of intellectual disability. The normal function of this gene and its protein is known to a certain extent. The UPF3B protein plays a role of a guardian of other genes in human (and also other species) cells. The role of the UPF3B protein is to prevent erroneous genetic information to be used for the building of proteins with potentially toxic effects to the organism. In our patients this process clearly malfunctions as a consequence of the damaged UPF3B gene. We propose to shed some more light in to the molecular intricacies of this process with the aim to better understand the mechanics of the process. Families, which participate in our studies and have this gene involved will benefit from the availability of direct test. Multiple other families around the world are also likely to benefit, now or in the future.Read moreRead less
Build competency aware and assuring machine learning systems. Recent development in machine learning (ML) has seen ML models with extremely high prediction accuracy. However, to support human-machine partnership in decision-making in complex environments, beyond accuracy, it is essential for ML systems to be competency aware and reliable, and at the same time be exploratory. This project aims to develop novel techniques to equip a ML system with the ability to identify own competency, to justify ....Build competency aware and assuring machine learning systems. Recent development in machine learning (ML) has seen ML models with extremely high prediction accuracy. However, to support human-machine partnership in decision-making in complex environments, beyond accuracy, it is essential for ML systems to be competency aware and reliable, and at the same time be exploratory. This project aims to develop novel techniques to equip a ML system with the ability to identify own competency, to justify its competency and decisions, to explore unknown situations and fully utilise existing expertise to deal with unknowns. The expected outcomes of the project will enable ML systems to become truely intelligent and reliable machine partners for human decision makers in a wide range of applications.Read moreRead less
Towards knowledge discovery from imperfect and evolving data. Information extraction from data is critical, both to analyse and protect consumer data. However, many learning techniques are developed using perfect, static datasets, quite different to messy, ever-changing real-world data. This project aims to develop data analytics techniques that can extract accurate information in complex structures from imperfect/incomplete data that changes over time. Expected outcomes are a prototype tool, te ....Towards knowledge discovery from imperfect and evolving data. Information extraction from data is critical, both to analyse and protect consumer data. However, many learning techniques are developed using perfect, static datasets, quite different to messy, ever-changing real-world data. This project aims to develop data analytics techniques that can extract accurate information in complex structures from imperfect/incomplete data that changes over time. Expected outcomes are a prototype tool, tested on real datasets, that combines new techniques in data modelling, algorithm development, and system design. Likely benefits are enhanced Australia's competence in data science through student training and new, robust data tools relevant to critical sectors such as cybersecurity, healthcare, and defence.Read moreRead less
Tapasin And Major Histocompatibility Complex Class I Antigen Presentation
Funder
National Health and Medical Research Council
Funding Amount
$226,650.00
Summary
An effective T cell response (cellular immune response) to infections is vital to a functional immune system. Normally, proteins are cleaved into small molecules called peptides and these peptides are in turn presented by Major Histocompatibility Complex molecules to T cells. However, we have only partial understanding of what determines the choice of peptides that are finally presented to T cells. Recent research suggests that a molecule called tapasin may also influence the choice of peptides. ....An effective T cell response (cellular immune response) to infections is vital to a functional immune system. Normally, proteins are cleaved into small molecules called peptides and these peptides are in turn presented by Major Histocompatibility Complex molecules to T cells. However, we have only partial understanding of what determines the choice of peptides that are finally presented to T cells. Recent research suggests that a molecule called tapasin may also influence the choice of peptides. This research proposal aims to examine the role of tapasin in this regard. A thorough understanding of the basic principles of peptide presentation to T cells is crucial to the design of effective vaccines. Furthermore it will also broaden our understanding of immunological responses to cancer, autoimmune diseases and infections.Read moreRead less