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NHMRC Medical Bioinformatics Genomics and Proteomics Program
Title Bioinformatic analysis and functional genomics
Investigation Team Professor Terence P Speed
Dr Gordon K Smyth
Dr Melanie Bahlo
Institution Walter & Eliza Hall Institute
State VIC
Recommended budget $2,450,000 over 5 years
Synopsis: We propose an integrated program of bioinformatics research and capacity building focused on functional genomics. We will address research problems in the analysis and interpretation of high-volume genomic and proteomic data, in comparative sequence analysis, in determining the relation between genotype and phenotype using mutagenesis screens, and in making effective use of single nucleotide polymorphisms. Our capacity building will focus on the research training of students (undergraduates through the UROP scheme, honours and PhD) and postdoctoral scholars.
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Title Genomic and Proteomic Profiling of Dendritic Cell Heterogeneity
Investigation Team Professor Ken Shortman
Dr William R Heath
Dr Jose Villandangos
Dr Mireille Lahoud
Professor Richard Simpson
Dr Mark Wright
Dr Sebastian Amigorena
Institution Walter & Eliza Hall Institute
State VIC
Recommended budget $1,971,250 over 5 years
Synopsis: Dendritic cells (DC) present antigens to T cells and regulate immunity and tolerance. DC are heterogeneous, comprising seven functionally distinct subsets. We will use genomics and proteomics to identify the plasma membrane and endosomal proteins that underpin this functional heterogeneity. Such proteins are potential targets for improved protocols of vaccination and prevention of autoimmunity. This project will thus provide further opportunities for high-quality research and commercialisation.
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Title Phosphoproteomics: metabolic and exercise signalling markers for sedentary and trained individuals
Investigation Team Professor Bruce Kemp
A/Professor Bostjan Kobe
Institution St.Vincent's Institute of Medical Research
State VIC
Recommended budget $1,222,500 over 5 years
Synopsis: It is widely recognized that diet and exercise have a major influence on the health and fitness.
Sedentary lifestyles predispose people to obesity and the early development of age onset diseases. In the past decade we have gained considerable insight into the regulatory links between exercise and metabolism particularly involving the AMPK signalling pathway. This project is concerned with the "phosphoproteome" of trained and untrained skeletal muscle, fat and erythrocytes as a marker of fitness.
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Title The Australian Medical Bioinformatics Resource (AMBeR)
Investigation Team Professor Lyle Palmer
Professor John L Hopper
Professor Fiona J Stanley
Professor Bruce K Armstrong
Professor Adrian J Baddeley
Professor John A Eisman
A/Professor James Semmens
Institution University of Western Australia
State WA
Recommended budget $2,185,000 over 5 years
Synopsis: This proposal is to build a new national medical bioinformatics resource - the Australian Medical Bioinformatics Resource (AMBeR) - and to enhance the national capacity in this important area. We aim to bring together Australia's unique resources for genetic epidemiology and genomics with high level expertise in bioinformatics and statistical science, conduct advanced methodological research, develop new research capacity and competitiveness in cutting-edge techniques, bring them to bear on important medical research problems, train young Australians in bioinformatics and advanced biostatistics, and transfer this expertise to the medical research community.
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Title Genome-wide combined linkage-association scan of multiply phenotyped twin sibships
Investigation Team Professor Nick Martin
Dr Grant Montgomery
Dr David Duffy
Professor Peter Visscher
Institution Queensland Institute of Medical Research
State QLD
Recommended budget $1,920,000 over 5 years
Synopsis: We have a large ongoing study of adolescent twins, their siblings and parents who are multiply phenotyped in many domains including melanoma risk factors, serum biochemistry, and cognition. We used our first Medical Genomics grant to obtain a 5cM linkage scan for>500 families and have identified linkage peaks for many different phenotypes. To fine map these it will be most efficient to carry out a genome-wide association scan. We request funds to type a 500k SNP chip on 1000 individuals.
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Title Retroviral Expression Cloning Using an Arrayed Full Length cDNA Gene Set
Investigation Team Professor Tom Gonda
Dr Brian Gabrielli
Dr Sean Grimmond
Dr Simon Barry
Institution University of Queensland
State QLD
Recommended budget $1,841,500 over 5 years
Synopsis: The sequencing of the human genome has revealed the blueprint for life, but the identities and/or functions of the majority of genes remain unknown. Here we propose to establish a radically modified retroviral expression cloning system that will, in principle, allow identification of all genes that confer a particular dominant phenotype. To do this we will establish an arrayed retroviral library of sequence-verified genes covering the entire human transcriptome. This technology will be used to identify genes involved in a wide range of medically-important biological processes.
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Title Statistical methods and algorithms for analysis of high-throughput genetics and genomics platforms.
Investigation Team Professor Peter Visscher
Professor Kerrie Mengersen
Dr David Duffy
Dr Dale Nyholt
Institution Queensland Institute of Medical Research
State QLD
Recommended budget $1,557,500 over 5 years
Synopsis: 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.
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Title Use of the Norfolk Island Genetic Isolate for Disease Gene Mapping
Investigation Team Professor Lyn Griffiths
Dr John Blangero
Dr Rod Lea
Institution Griffith University
State QLD
Recommended budget $978,500 over 3years
Synopsis: 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 18 th 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.
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