Expression Genomics - Sean Grimmond

Professor Sean Grimmond

The Queensland Centre for Medical Genomics (QCMG) was officially opened by the Premier of Queensland, the Hon. Anna Bligh, on June 16, 2010. The laboratory is focused on globally surveying genomic, transcriptomic and epigenomic information using next-generation sequencing and array-based approaches, and then integrating this data to define the underlying molecular networks controlling biological processes (such as cell division and differentiation) and pathological states (pancreatic, ovarian and breast cancer). This systems-wide approach will provide the means to identify key genes driving specific phenotypes and also the chance to model the different layers of control guiding biological states.

Defining the complete repertoire of mutations driving pancreatic and ovarian cancer development and progression: The next-generation sequencing facility at QCMG has been actively scaling the output required for the International Cancer Genome Consortium (ICGC) project with Australia’s contribution covering pancreatic cancer and a smaller subset of ovarian cancer patients. The informatics pipelines needed to handle the data output have been established with many of the tools created in house; the focus for the informatics group over the next 12 months will be on automating many of the manual steps still used which will allow the ICGC project to be scaled appropriately. The ICGC’s ultimate aim is to create comprehensive genomic, transcriptomic and epigenomic atlases of the molecular changes arising in human tumours. The consortium will achieve this by characterising up to 50 different tumor types and/or subtypes from across the globe over the next five years.

Studying mammalian transcriptomes at single nucleotide resolution: We are continuing to actively survey the transcriptional complexity in specific biological states using a next-generation sequencing approach (RNAseq) in 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). It also provides an opportunity to study novel expression events (including retrotransposon expression, the complexity in small RNAs and identification of novel non-coding RNAs). We are actively engaged in RNAseq studies to create a human and mouse tissue transcriptome atlas, study transcriptome complexity in human Embryonic Stem Cells (hESCs) and inducible Pluripotent (iPS) cells, as well as surveying transcriptome content during the cell cycle.

Research Projects

• Predicting the function of onco-miRs through miRNA-mRNA networks


• Defining the complete repertoire of genetic damage driving development and progression of breast cancer in a mouse model


• Sequencing the mammalian transcriptome in toto


• Phasevarions of pathogenic neisseria


• Functionally characterising mammalian microRNA-mRNA interactions

Key Publications

Chiu, H.-S., Szucsik, J.C., Georgas, K.M., Jones, J.L., Rumballe, B.A., Tang, D., Grimmond, S.M., Lewis, A.G., Lessard, J.L., Aronow, B.J., and Little, M.H. (2010). A comprehensive catalogue of gene expression in the developing lower urinary tract and genital tubercle reveals strong links with cadherin and Wnt signaling and identifies epidermal gene networks in the developing genital tubercle. Developmental Biology 344: 1071-1087.

Cloonan, N., and Grimmond, S.M. (2010). Simplifying Complexity. Nature Methods 7: 793-795.

Mercer, T.R., Dinger, M.E., Bracken, C.P., Kolle, G., Szubert, J.M., Korbie, D.J., Askarian-Amiri, M.E., Gardiner, B.B., Goodall, G.J., Grimmond, S.M., and Mattick, J.S. (2010). Regulated post-transcriptional RNA cleavage diversifies the eukaryotic transcriptome. Genome Research 20: 1639-1650.

Schmeier, S., Kanamori-Katayama, M., Bertin, N., Carninci, P., Daub, C.O., Forrest, A.R.R., Gough, J., Grimmond, S.M., Han, J.-H., Hashimoto, T., Hide, W., Hofmann, O., Kawaji, H., Kubosaki, A., Lassmann, T., van Nimwegen, E., Ogawa, C., Teasdale, R.D., Tegnér, J., Lenhard, B., Teichmann, S.A., Arakawa, T., Ninomiya, N., Murakami, K., Tagami, M., Fukuda, S., Imamura, K., Kai, C., Ishihara, R., Kitazume, Y., Kawai, J., Hume, D.A., Ideker, T., and Hayashizaki, Y. (2010). An Atlas of Combinatorial Transcriptional Regulation in Mouse and Man. Cell 140: 744-752.

Tallack, M., Whitington, T., Cloonan, N., Bailey, T.*, Grimmond, S.M.*, and Perkins, A.* (Corresponding authors) (2010). A global role for KLF1 in erythropoiesis revealed by ChIP-seq in primary erythroid cells. Genome Research 20: 1052-1063.

The International Cancer Genome Consortium (SM Grimmond listed as leader of the Australian project & member of the technology and scientific steering committees) (2010). International network of cancer genome projects. Nature 464: 993-998.

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