Defining the repertoire of mutations driving cancer development and progression

Next generation sequencing technology has heralded new opportunities for cancer genomic research. It is now feasible to survey the entire sequence content of an individual tumour and define the accumulation of somatic mutations and structural variations. We are undertaking the systematically surveying of complete transcriptome complexity, genome sequence content / genome structure and epigenomic signatures in a large cohort of individual Pancreatic Cancers (in collaboration with A. Biankin, Gavan Institute) and Ovarian Cancers (in collaboration with D. Bowtell, PeterMac Cancer Institute) as part of the International Cancer Genome Consortium. [read more]

Studying Transcriptional Complexity

The mammalian Transcriptome is far more complicated than previously thought. Our group has used bioinformatics to review the transcriptional output of all loci in mouse and man, providing novel insights into how alternative transcription expands the repertoire of the proteome and provides higher levels of control of biological systems. [read more]

Studying mammalian transcriptomes at single nucleotide resolution:

Previously, we have used bioinformatic approaches to review the transcriptional output of all loci in mouse and man, and provided novel insights into how alternative transcription expands the repertoire of the proteome and provides higher levels of control of biological systems. We are now actively pursuing the role of this transcriptional complexity in specific biological statesĀ using next-generation sequencing approaches [read more]

Predicting the function of miRNA-mRNA networks:

MicroRNAs (miRNAs) are short, non-coding, RNA regulators of gene expression that have been identified in a broad range of eukaryotes. In addition to regulating growth, development, differentiation, some miRNAs have also been classified as tumour suppressors or oncogenes. We have recently developed a systems biology approach to uncover large networks of interacting genes that are directly targeted by miRs and predict their function. We are now expanding our endeavors to explore the mammalian miRNA and mRNA transcriptomes and search for novel functional miRNA-mRNA networks [read more]

Phosphoregulators: Systems biology of the kinome and phosphatome

Phosphoregulators Massive scale transcriptome and genome annotation efforts have recently identified all genes encoding the cellular machinery of protein phosphorylation. These molecular networks have been found to be far more complex in mammals than previously reported, with many kinase and phosphatase loci generating, on average, more than 6 transcripts per gene through the process of alternative splicing. We are modelling phosphoregulator networks and addressing the impact transcriptional complexity has on the control of normal cell division and tumorigenesis using system-based approaches. [read more]

Computational & Genomic characterisation of the Extracellular Space

ECS pipeline Intercellular communication underpins the entire processes of differentiation and development, and defines interactions between cells, tissues, and organs. With the completion of the human and mouse genomes, it is now possible to predict the entire set of ligands and receptors. [read more]

Systems approaches to ES Cell maintenance and differentiation

In this area of our research, we are using transcriptomic, bioinformatic and high throughput platform technologies to find lead compounds for the maintenance of human and mouse ES cell pluripotency and directed differentiation. [read more]

Transcriptome Studies of Kidney Development and Renal repair

SCGAP As part of the NIDDK's Stem Cell Genome Anatomy Project (SCGAP) we created a temporal and spatial transcriptome atlas of the developing mouse kidney (10.5dpc-adult). More recently, as part of the NIH Genitourinary Development Map program (GUDmap), we have undertaken surveying the histological expression patterns of several thousand genes in the normal mouse kidney (both embryonic and adult) via automated in situ hybridisation, providing us with a detailed temporal and spatial molecular atlas of normal metanephric development. This is forming the foundation for several studies into developmental gene networks, the role of extracellular signals in kidney organogenesis and renal repair. [read more]

Microarray Technology

Illumina The Expression Genomics laboratory has overseen microarray technology at the IMB since its inception of the array facility in 2001 - pioneering expression profiling using all major array platforms, fabrication of spotted high-density oligonucleotide and cDNA arrays and the design of customised arrays for targeting novel transcripts (non-coding RNAs) and splicing events. [read more]

ARVEC - Arrayed RetroViral Expression Cloning

ARVECThe ARVEC project aims to establish (1) an arrayed retroviral library of sequence-verified full-length cDNA clones covering the human transcriptome and (2) an automated, high-throughput facility for virus production, target cell transduction and screening. [read more]

Developmental Imaging and Laser Capture Microscopy

In 2006, the Expression Genomics laboratory established an IMB developmental imaging suite. The suite consists of automated technologies for in situ hybridisation, automated imaging and state of the art laser capture microscopy. [read more]

Next Generation Sequencing

Recent advances in nanotechnology have heralded new opportunities for DNA sequencing and genomic research. Applied Biosystems Inc (AB) have developed a single molecule sequencing approach based on Church's "polony" sequencing concept. Known as Supported Oligo Ligation Detection Sequencing (SOLiD), this technology provides the means to sequence short DNA fragments at rates of more than 100,000,000 sequences per run. [read more]