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Department of Biochemistry profile

Dr Chris Brown

PositionSenior Lecturer
DepartmentDepartment of Biochemistry
QualificationsMSc PhD(Otago)
Research summaryRegulatory genomics
TeachingGenetics and Biochemistry: BIOC 221, GENE 223, BIOC 352, BIOC 451, GENE 400, PLBI 401, MICN 201 (Genetics, Blood), MICN 301 (Genetics).

Research

Regulatory Genomics

The identification of novel regulatory elements and genes.

Gene expression must be carefully regulated in all species. We are investigating this regulation using bioinformatics and wet experiments in a range of systems. Software and datasets from the Brown group are available through our servers, by download, or through collaborators. Current projects involve the use of both computer and experimental tools to test for new types of control mechanisms.

Databases and tools for genomics.

The recent availability of large amounts of sequence data, particularly complete genome sequences and transcriptomes and proteomes, has revolutionised the study of gene expression. Our first tool (TransTerm) began over 20 years ago, it includes data and tools related to translation. Virus research tools and databases include HBVRegDB, CRISPRTarget and CRISPRSuite.

A listing of tools and their applications is on the Bioanalysis website.

Gene discovery using comparative genomics

We are using high throughput genomic from several diverse organisms, in collaboration with other groups (see collaborations). These studies include aiming to identify coding and non-coding RNAs and regulatory elements in these genomes. Applications include - plant pathogen and endophyte interactions, methanogen genomes, and pathogenic bacterial and viral genomes and viromes.

Potential PhD (Doctoral) or MSc research projects

There are several exciting projects available to students including Bioinformatics, Virology or Cell Biology or a mix of these. The balance of the approach would depend on the skills and interests of the person (e.g. Bioinformatics, Genetics, Genomics). These could be supervised in collaborations (e.g. with CRIs or other Otago Researchers). Please send a CV including academic references and reason why you are interested in that project to me.

Indicative projects (for 2019–2020)

  • Discovery of viruses in genomic and virome sequences
  • Genomic and transcriptomic approaches to reducing agricultural greenhouse gas emissions (jointly supervised with collaborators).
  • Discovery of key features of the bacterial adaptive immune system (CRISPR-Cas). Jointly supervised by Dr Peter Fineran (Microbiology and Immunology).
  • Plant/Fungal interactions and genomics (with Dr David Orlovich, Botany)

More information on fellowships and scholarships can be found on the University of Otago postgraduate pages.

Current collaborations

  • Peter Fineran (Otago, Microbiology). The discovery of CRISPR elements in bacterial genomes and their targets in viral (bacteriophage) genomes.
  • David Orlovich and Tina Summerfield (Botany) New Zealand native mushroom genomes (Taonga).
  • Artemio Mendoza (Bio-Protection, Lincoln) Genomics of fungal-plant interactions - Gene expression bioinformatics. Fungal non-coding RNAs.
  • Abigail Smith (Marine Science) Bryozoan genomics

Thanks to past and present funding agencies

  • Dunedin School of Medicine Bequest Funds
  • University of Otago Research Grants
  • Human Frontier Science Organisation
  • Health Research Council
  • Lotteries Health
  • The Marsden Fund
  • Joint Genome Institute

I am interested in contacts from potential collaborators, postdoctoral fellows, and graduate students.

Publications

Shehreen, S., Chyou, T.-y., Fineran, P. C., & Brown, C. M. (2019). Genome-wide correlation analysis suggests different roles of CRISPR-Cas systems in the acquisition of antibiotic resistance genes in diverse species. Philosophical Transactions of the Royal Society B, 374(1772), 20180384. doi: 10.1098/rstb.2018.0384

Nilsen, A. R., Brown, C. M., Summerfield, T. C., & Orlovich, D. A. (2019). Cortinarius atropileatus sp. nov. (Cortinariaceae) from New Zealand. New Zealand Journal of Botany, 57(1), 50-61. doi: 10.1080/0028825X.2018.1548493

Chyou, T., & Brown, C. M. (2018). Prediction and diversity of tracrRNAs from type II CRISPR-Cas systems. RNA Biology. Advance online publication. doi: 10.1080/15476286.2018.1498281

Lim, C. S., Wardell, S. J. T., Kleffmann, T., & Brown, C. M. (2018). The exon-intron gene structure upstream of the initiation codon predicts translation efficiency. Nucleic Acids Research. Advance online publication. doi: 10.1093/nar/gky282

Nicholson, T. J., Jackson, S. A., Croft, B. I., Staals, R. H. J., Fineran, P. C., & Brown, C. M. (2018). Bioinformatic evidence of widespread priming in Type I and II CRISPR-Cas systems. RNA Biology. Advance online publication. doi: 10.1080/15476286.2018.1509662

Chapter in Book - Research

Biswas, A., Fineran, P. C., & Brown, C. M. (2015). Computational detection of CRISPR/crRNA targets. In M. Lundgren, E. Charpentier & P. C. Fineran (Eds.), CRISPR: Methods in molecular biology (Vol. 1311). (pp. 77-89). New York, NY: Humana Press. doi: 10.1007/978-1-4939-2687-9_5

Stevens, S. G., & Brown, C. M. (2014). Bioinformatic methods to discover Cis-regulatory elements in mRNAs. In N. K. Kasabov (Ed.), Springer handbook of bio-/neuro-informatics. (pp. 151-169). Dordrecht, The Netherlands: Springer. doi: 10.1007/978-3-642-30574-0_10

Brown, C., Schreiber, M. J., Chapman (Nee Hobbs), B., & Jacobs, G. H. (2000). Information Science and Bioinformatics. In Future Directions for Intelligent Systems and Information Science. (pp. 251-287). Heidelberg, Germany: Springer-Verlag.

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Journal - Research Article

Shehreen, S., Chyou, T.-y., Fineran, P. C., & Brown, C. M. (2019). Genome-wide correlation analysis suggests different roles of CRISPR-Cas systems in the acquisition of antibiotic resistance genes in diverse species. Philosophical Transactions of the Royal Society B, 374(1772), 20180384. doi: 10.1098/rstb.2018.0384

Nilsen, A. R., Brown, C. M., Summerfield, T. C., & Orlovich, D. A. (2019). Cortinarius atropileatus sp. nov. (Cortinariaceae) from New Zealand. New Zealand Journal of Botany, 57(1), 50-61. doi: 10.1080/0028825X.2018.1548493

Chyou, T., & Brown, C. M. (2018). Prediction and diversity of tracrRNAs from type II CRISPR-Cas systems. RNA Biology. Advance online publication. doi: 10.1080/15476286.2018.1498281

Nicholson, T. J., Jackson, S. A., Croft, B. I., Staals, R. H. J., Fineran, P. C., & Brown, C. M. (2018). Bioinformatic evidence of widespread priming in Type I and II CRISPR-Cas systems. RNA Biology. Advance online publication. doi: 10.1080/15476286.2018.1509662

Lim, C. S., Wardell, S. J. T., Kleffmann, T., & Brown, C. M. (2018). The exon-intron gene structure upstream of the initiation codon predicts translation efficiency. Nucleic Acids Research. Advance online publication. doi: 10.1093/nar/gky282

Biswas, A., Staals, R. H. J., Morales, S. E., Fineran, P. C., & Brown, C. M. (2016). CRISPRDetect: A flexible algorithm to define CRISPR arrays. BMC Genomics, 17, 356. doi: 10.1186/s12864-016-2627-0

Schmoll, M., Dattenböck, C., Carreras-Villaseñor, N., Mendoza-Mendoza, A., Tisch, D., Alemán, M. I., … Brown, C., … Herrara-Estrella, A. (2016). The genomes of three uneven siblings: Footprints of the lifestyles of three Trichoderma species. Microbiology & Molecular Biology Reviews, 80(1), 205-327. doi: 10.1128/mmbr.00040-15

Hellens, R. P., Brown, C. M., Chisnall, M. A. W., Waterhouse, P. M., & Macknight, R. C. (2016). The emerging world of small ORFs. Trends in Plant Science, 21(4), 317-328. doi: 10.1016/j.tplants.2015.11.005

Lim, C. S., & Brown, C. M. (2016). Hepatitis B virus nuclear export elements: RNA stem-loop α and β, key parts of the HBV post-transcriptional regulatory element. RNA Biology, 13(9), 743-747. doi: 10.1080/15476286.2016.1166330

Staals, R. H. J., Jackson, S. A., Biswas, A., Brouns, S. J. J., Brown, C. M., & Fineran, P. C. (2016). Interference-driven spacer acquisition is dominant over naive and primed adaptation in a native CRISPR–Cas system. Nature Communications, 7, 12853. doi: 10.1038/ncomms12853

Bond, D. M., Albert, N. W., Lee, R. H., Gillard, G. B., Brown, C. M., Hellens, R. P., & Macknight, R. C. (2016). Infiltration-RNAseq: Transcriptome profiling of Agrobacterium-mediated infiltration of transcription factors to discover gene function and expression networks in plants. Plant Methods, 12, 41. doi: 10.1186/s13007-016-0141-7

Davies, C., Brown, C. M., Westphal, D., Ward, J. M., & Ward, V. K. (2015). Murine norovirus replication induces a G0/G1 cell cycle arrest in asynchronous growing cells. Journal of Virology, 89(11), 6057-6066. doi: 10.1128/jvi.03673-14

Waugh, E., Chen, A., Baird, M. A., Brown, C. M., & Ward, V. K. (2014). Characterization of the chemokine response of RAW264.7 cells to infection by murine norovirus. Virus Research, 181, 27-34. doi: 10.1016/j.virusres.2013.12.025

Gillard, G. B., Garama, D. J., & Brown, C. M. (2014). The transcriptome of the NZ endemic sea urchin Kina (Evechinus chloroticus). BMC Genomics, 15, 45. doi: 10.1186/1471-2164-15-45

Biswas, A., Fineran, P. C., & Brown, C. M. (2014). Accurate computational prediction of the transcribed strand of CRISPR noncoding RNAs. Bioinformatics, 30(13), 1805-1813. doi: 10.1093/bioinformatics/btu114

Chen, A., T-Thienprasert, N. P., & Brown, C. M. (2014). Prospects for inhibiting the post-transcriptional regulation of gene expression in hepatitis B virus. World Journal of Gastroenterology, 20(25), 7993-8004. doi: 10.3748/wjg.v20.i25.7993

Biswas, A., & Brown, C. M. (2014). Scan for Motifs: A webserver for the analysis of post-transcriptional regulatory elements in the 3’ untranslated regions (3’ UTRs) of mRNAs. BMC Bioinformatics, 15, 174. doi: 10.1186/1471-2105-15-174

Stevens, S. G., & Brown, C. M. (2013). In silico estimation of translation efficiency in human cell lines: Potential evidence for widespread translational control. PLoS ONE, 8(2), e57625. doi: 10.1371/journal.pone.0057625

Biswas, A., Gagnon, J. N., Brouns, S. J. J., Fineran, P. C., & Brown, C. M. (2013). CRISPRTarget: Bioinformatic prediction and analysis of crRNA targets. RNA Biology, 10(5), 817-827. doi: 10.4161/rna.24046

Chen, A., & Brown, C. (2012). Distinct families of cis-acting RNA replication epsilon elements from hepatitis B viruses. RNA Biology, 9(2), 130-136. doi: 10.4161/rna.18649

Lange, S. J., Maticzka, D., Möhl, M., Gagnon, J. N., Brown, C. M., & Backofen, R. (2012). Global or local? Predicting secondary structure and accessibility in mRNAs. Nucleic Acids Research, 40(12), 5215-5226. doi: 10.1093/nar/gks181

Chen, X. S., & Brown, C. M. (2012). Computational identification of new structured cis-regulatory elements in the 3’-untranslated region of human protein coding genes. Nucleic Acids Research, 40(18), 8862-8873. doi: 10.1093/nar/gks684

Pilbrow, A. P., Folkersen, L., Pearson, J. F., Brown, C. M., McNoe, L., Wang, N. M., … Black, M. A., Troughton, R. W., Richards, A. M., … Cameron, V. A. (2012). The chromosome 9p21.3 coronary heart disease risk allele is associated with altered gene expression in normal heart and vascular tissues. PLoS ONE, 7(6), e39574. doi: 10.1371/journal.pone.0039574

Panjaworayan, N., & Brown, C. M. (2011). Effects of HBV genetic variability on RNAi strategies. Hepatitis Research & Treatment, 2011, 367908. doi: 10.1155/2011/367908

Stevens, S. G., Gardner, P. P., & Brown, C. (2011). Two covariance models for iron-responsive elements. RNA Biology, 8(5), 792-801. doi: 10.4161/rna.8.5.16037

Milev, M. P., Brown, C. M., & Mouland, A. J. (2010). Live cell visualization of the interactions between HIV-1 Gag and the cellular RNA-binding protein Staufen1. Retrovirology, 7, 41. doi: 10.1186/1742-4690-7-41

Panjaworayan, N., Payungporn, S., Poovorawan, Y., & Brown, C. M. (2010). Identification of an effective siRNA target site and functional regulatory elements, within the hepatitis B virus posttranscriptional regulatory element. Virology Journal, 7, 216. doi: 10.1186/1743-422x-7-216

Jacobs, G. H., Chen, A., Stevens, S. G., Stockwell, P. A., Black, M. A., Tate, W. P., & Brown, C. M. (2009). Transterm: A database to aid the analysis of regulatory sequences in mRNAs. Nucleic Acids Research, 37(Database issue), D72-D76. doi: 10.1093/nar/gkn763

Panjaworayan, N., Roessner, S. K., Firth, A. E., & Brown, C. M. (2007). HBVRegDB: Annotation, comparison, detection and visualization of regulatory elements in hepatitis B virus sequences. Virology Journal, 4, 136. Retrieved from http://www.virologyj.com/content/4/1/136

Zadissa, A., McEwan, J. C., & Brown, C. M. (2007). Inference of transcriptional regulation using gene expression data from the bovine and human genomes. BMC Genomics, 8, 265. doi: 10.1186/1471-2164-8-265

Firth, A. E., & Brown, C. M. (2006). Detecting overlapping coding sequences in virus genomes. BMC Bioinformatics, 7, 75. doi: 10.1186/1471-2105-7-75

Jacobs, G. H., Stockwell, P. A., Tate, W. P., & Brown, C. M. (2006). Transterm: Extended search facilities and improved integration with other databases. Nucleic Acids Research, 34(Database), D37-D40.

Chung, B. Y. W., Simons, C., Firth, A. E., Brown, C. M., & Hellens, R. P. (2006). Effect of 5'UTR introns on gene expression in Arabidopsis thaliana. BMC Genomics, 7, 120. doi: 10.1186/1471-2164-7-120

Chen, A., Kao, Y. F., & Brown, C. M. (2005). Translation of the first upstream ORF in the hepatitis B virus pregenomic RNA modulates translation at the core and polymerase initiation codons. Nucleic Acids Research, 33(4), 1169-1181.

Firth, A. E., & Brown, C. M. (2005). Detecting overlapping coding sequences with pairwise alignments. Bioinformatics, 21(3), 282-292.

Chapman, B., & Brown, C. (2004). Translation termination in Arabidopis thaliana: Characterisation of three versions of release factor 1. Gene, 341, 219-225.

Rackham, O., & Brown, C. M. (2004). Visualization of RNA-protein interactions in living cells: FMRP and IMP1 interact on mRNAs. EMBO Journal, 23(16), 3346-3355.

Jacobs, G. H., Rackham, O., Stockwell, P. A., Tate, W. P., & Brown, C. M. (2002). Transterm: a database of mRNAs and translational control elements. Nucleic Acids Research, 30, 310-311.

Schreiber, M., & Brown, C. (2002). Compensation for nucleotide bias in a genome by representation as a discrete channel with noise. Bioinformatics, 18(4), 507-512.

Jacobs, G. H., Stockwell, P. A., Schreiber, M. J., Tate, W. P., & Brown, C. M. (2000). Transterm: A database of messenger RNA components and signals. Nucleic Acids Research, 28, 293-295.

Dalphin, M. E., Stockwell, P. A., Tate, W. P., & Brown, C. M. (1999). TransTerm, the translational signal database, extended to include full coding sequences and untranslated regions. Nucleic Acids Research, 27, 293-294.

Brown, C. M., Jacobs, G. H., Schreiber, M. J. J., Magnum, J., McNaughton, J. C., Cambray, M., Futschik, M., Major, L. L., Rackham, O., Tate, W. P., … Stockwell, P. A., & Kasabov, N. K. (1999). Using bioinformatics to investigate post-transcriptional control of gene expression. New Zealand BioScience, 7, 11-12.

Dalphin, M. E., Brown, C. M., Stockwell, P. A., & Tate, W. P. (1998). The translational signal database, TransTerm, is now a relational database. Nucleic Acids Research, 26, 335-337.

Miller, W. A., Brown, C., & Wang, S. (1997). New punctuation for the genetic code: Luteovirus gene expression. Seminars in Virology, 8, 3-13.

Dalphin, M. E., Brown, C. M., Stockwell, P. A., & Tate, W. P. (1997). The translational signal database, TransTerm: more organisms, complete genomes. Nucleic Acids Research, 25, 246-247.

Brown, C. M., Dinesh-Kumar, S. P., & Miller, W. A. (1996). Local and distant sequences are required for efficient readthrough of the barley yellow dwarf virus PAV coat protein gene stop codon. Journal of Virology, 70, 5884-5892.

Dalphin, M. E., Brown, C., Stockwell, P. A., & Tate, W. P. (1996). TransTerm: a database of translational signals. Nucleic Acids Research, 24, 216-218.

Tate, W. P., Poole, E. S., Horsfield, J. A., Mannering, S. A., Brown, C. M., Moffat, J. G., Dalphin, M. E., … Major, L. L., & Wilson, D. N. (1995). Translational termination efficiency in both bacteria and mammals is regulated by the base following the stop codon. Biochemistry & Cell Biology, 73, 1095-1103. doi: 10.1139/o95-118

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Journal - Research Other

Tate, W. P., Cridge, A. G., & Brown, C. M. (2018). 'Stop' in protein synthesis is modulated with exquisite subtlety by an extended RNA translation signal. Biochemical Society Transactions, 46(6), 1615-1625. doi: 10.1042/bst20180190

Lim, C. S., & Brown, C. M. (2018). Know your enemy: Successful bioinformatic approaches to predict functional RNA structures in viral RNAs. Frontiers in Microbiology, 8, 2582. doi: 10.3389/fmicb.2017.02582

Lim, C. S., & Brown, C. (2017). A new class of ribozyme from hepatitis B virus. FEBS Journal, 284(8), 1182-1183. doi: 10.1111/febs.14062

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