The Australian ICGC Project
The Australian contingent of the ICGC initiative is based at the QCMG/IMB and will study the underlying changes that result in the development of pancreatic and ovarian cancer.
The Australian Pancreatic Cancer Genome Initiative (APGI), co-led by Professor Sean Grimmond from the Institute of Molecular Bioscience in Brisbane, and Professor Andrew Biankin from The Garvan Institute of Medical Research in Sydney, is the Australian project arm of the pancreatic cancer genome initiative.
It is made up of a range of specialists and researchers in pancreatic cancer across the country.
The initiative also includes significant contributions from centres across the globe including Johns Hopkins University and the University of California in the USA, the Ontario Institute for Cancer Research in Canada and the University of Verona in Italy.
Another component of the QCMG will be the sequencing of a set of ovarian cancer tumours through partnership with Professor David Bowtell from the Peter MacCallum Cancer Centre.
Professor Bowtell is part of the Australian Ovarian Cancer Study (AOCS) which is a collaborative research program between clinicians, scientists, patients and advocacy groups aimed at improving the prevention, diagnosis, and treatment of ovarian cancer.
Initiated in 2001 AOCS now has a uniquely powerful resource for ovarian cancer research comprised of bio-specimens, clinical and epidemiological data, ensuring that the QCMG will have samples meeting the ICGC and NHMRC criteria.
A major goal of the study is to identify genetic and biochemical changes in patient’s cancers that dictate responsiveness to chemotherapy and overall patient survival.
QCMG RESEARCH PROJECTSStudying mammalian transcriptomes at single nucleotide resolution
The mammalian Transcriptome is far more complicated than previously thought. Rather than each gene encoding a single mRNA, it now appears human loci are capable of an average 6-7 RNAs.
We are actively surveying this transcriptional complexity in specific biological states using a next-generation sequencing approach (RNAseq) and an effort to put newly discovered transcripts into a functional context.
RNAseq supersedes traditional array based expression profiling as it allows us to simultaneously monitor gene activity, study alternative splicing events, identify promoter and 3' UTR usage, and capture expressed sequence variation (SNPs and mutations). The QCMG is actively engaged in RNAseq studies of the following areas:
- Creating a human and mouse tissue transcriptome atlas
- Human Embryonic Stem Cells (hESCs) including Pluripotent (iPS) cells
- Human Cell Cycle synchronized cells
- Human Cancer cell lines
Projects are currently funded by the Australian Stem Cell Centre, the Australia Research Council and Australian National Health & Medical Research Council.
Characterizing mammalian microRNA-mRNA interactions
MicroRNAs (miRNAs) are crucial components of the regulatory circuitry of cells, modulating target gene activity and controlling key biological processes such as cell proliferation and cell death.
Although the mechanism for miRNA regulation is well understood, the biological role of most miRNAs remains unknown. The major is identifying their mRNA targets in vivo. Currently, the experimental methods for determining miRNA-mRNA interactions are laborious and expensive and computationally derived predictions are plagued with high false positive rates.
Ideally, one would isolate all RNA sequences to which the miRNA is bound in vivo, and identify them through sequencing, but until recently this approach has not been technically or economically feasible.
The QCMG will exploit recent advances in molecular biology and next-generation sequencing to elucidate the scale and scope of miRNA-mRNA interactions in mammalian to re-derive the rules of miRNA-mRNA interaction based on large-scale data sets.