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.
Molecular Profiling Of The Immunoglobulin Proteome In Primary Sjögren’s Syndrome
Funder
National Health and Medical Research Council
Funding Amount
$322,460.00
Summary
Primary Sjögren’s syndrome is a common autoimmune disease. The patients have high levels of circulating immunoglobulins (Igs) in their blood-a hallmark of the disorder. The applicant proposes to sequence these Igs and identify their so-called variable region molecular signatures. These signatures can then be used in a mass spectrometric-based diagnostic platform to identify unique clones in patients as early markers of the disease process, and hopefully lead to more relevant diagnostic markers.
Symmetries in real and complex geometry. This project concerns an important area of abstract modern geometry. The results and techniques of the project will lead to significant progress in this area. It will benefit the national scientific reputation, strengthen the research profile of the home institutions, and provide training to young researchers.
Synchrotron X-ray Assessment Of Airway Surface Physiology For Cystic Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$778,228.00
Summary
We seek a cure or long-lasting therapy for the fatal airway disease in cystic fibrosis. Disease is caused by a shallow and dehydrated airway surface liquid (ASL), allowing bacteria to infect the lung. We can introduce a corrective gene into mouse airways where it can be effective for over 1 yr, but no fast, accurate and non-invasive measurement exists to test if treatments are successful. We will develop methods using synchrotron light to directly measure ASL depth changes in live mouse airways.
Identification Of The Conformation Dependant Targets Of Autoimmune Disease Linked Variation In Human Regulatory T Cells
Funder
National Health and Medical Research Council
Funding Amount
$1,001,815.00
Summary
Specialised immune cells called regulatory T cells act as the policemen of the immune system, preventing the immune system attacking itself, but still fighting infections. If these cells do not work properly, autoimmune diseases such as type 1 diabetes or IBD can arise, because of immune attack on normal body tissue by mistake. In order to explain how this goes wrong we need to carefully identify all of the gene interactions in these cells including interactions over long distances in the DNA.
I am a molecular geneticist with a main research focus in the identification and characterisation of genes and molecular pathways involved in intellectual disability and epilepsy.
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
Operator Integrals and Derivatives. The project is a contribution to the study of non-commutative differential and integral calculus. The novelty of the present project lies in the study of smoothness properties of functions whose domains and ranges are spaces of unbounded, non-commuting operators on some Hilbert space. Our general approach will be based on a detailed investigation of properties of double operator integrals, which permit smoothness estimates of operator-functions. It can be expe ....Operator Integrals and Derivatives. The project is a contribution to the study of non-commutative differential and integral calculus. The novelty of the present project lies in the study of smoothness properties of functions whose domains and ranges are spaces of unbounded, non-commuting operators on some Hilbert space. Our general approach will be based on a detailed investigation of properties of double operator integrals, which permit smoothness estimates of operator-functions. It can be expected that the new techniques generated will find further application in areas of mathematical physics and non-commutative geometry related to quantized calculus.
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Non-commutative analysis and differential calculus. This project is in an area of central mathematical importance and will lead to important scientific advances that will keep Australia at the forefront internationally in this field of research. There is an emphasis on international networking and we will collaborate with leading researchers in USA and France.
Mechanisms Of Premature Cranial Fusion: Role Of Retinol Binding Protein 4 In Osteogenesis And Suture Fusion
Funder
National Health and Medical Research Council
Funding Amount
$555,855.00
Summary
Craniosynostosis is a condition where the skull bones fuse prematurely, affecting skull shape, vision and cognition. It occurs in 1 in 2,500 births. The only treatment is surgery, which is life-threatening, costly and may need to be repeated. By studying how fusion happens in this project we may be able to devise therapies to minimize the risks and need for re-operation. Here, we hope to show that modification of a single substance in the skull of mouse models can prevent premature bone fusion.