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Dr Betty Chung

Dr Betty Chung

Medical Research Council Fellow

Division of Microbiology and Parasitology

Translation control

Gene expression mechanisms

Ribosome profiling

RNA structure and function

Tennis Court Road, CB21QP
Cambridge, United Kingdom
Office Phone: +44 (0)1223 333331
Lab Phone: +44 (0)1223 333545

Biography:

Betty's research focuses on the dynamics of post-transcriptional control of gene expression. During her PhD, under the tutelage of Professor John Atkins, she was particularly interested in "non-canonical" mechanisms such as programmed ribosomal frame-shifting (animal virus) and programmed transcriptional slippage (plant virus). Her postdoctoral studies - supported by Long-Term EMBO and Sir Henry Wellcome Postdoctoral Fellowships and mentored by Professor Sir David Baulcombe - addressed the global effects and mechanism of miRNA-mediated gene regulation in plants. As a Medical Research Council Career-Development Fellow, her group in Department of Pathology aims to address both translational and transcriptional dynamics of immune cells during pathogen infection (Viruses, Toxoplasma, Salmonella and Listeria).

Research Interests

A major response of cells during pathogen infection is changes in gene expression, leading to changes in the proteins being produced in the cell. Proteins are essential biopolymers in all living organisms, playing roles as structural components of cells, enzymes, and immune response agents such as antibodies. Regulation of gene expression can occur at two levels: transcription (where mRNA is synthesised in the cell nucleus by the macromolecular machine RNA polymerase) and translation (where mRNA is decoded into proteins in the cell cytoplasm by the macromolecular machine known as the ribosome).
When cells are stressed, specific gene expression pathways are activated (e.g. cytokines as part of the innate immune system). However, so far, very few studies have systematically studied these changes in gene expression at the level of translation. The primary reason is due to technical difficulties with global monitoring of protein synthesis. Transcriptional regulation has been previously studied; however there is evidence that a significant amount of regulation also occurs at the translational level. This makes sense as direct modulation of protein synthesis provides a faster and more efficient response to pathogen infection, as it circumvents de novo mRNA transcription, processing and transport to the cell cytoplasm. Translational control is a highly dynamic process and global studies have only recently become possible with the advent of RiboSeq - a high-throughput technique that allows capturing the location and abundance of all ribosomes on mRNAs, allowing precise global measurement of real-time protein synthesis. We aim towards understanding the complex interplay of host and pathogen gene regulation, and its ultimate effect on the host proteome and host response to biotic stress.

Understanding biological role for translation responses during pathogen infection

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Mechanism of infection-dependent cis-regulatory RNA elements that modulates translation.

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Mechanism of infection-dependent trans-regulatory RNA elements

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Key Publications

Public resource development 

riboSeqR – Bioinformatic software package developed with Dr Thomas Hardcastle (Department of Plant Sciences) as part of the Bioconductor project, to assist the community in the analysis of Ribosome profiling data [Hardcastle and Chung 2018Chung et al.2015 RNA]

Peer reviewed publications

  • Chung, B. (co-corresponding author), Deery, M., Groen, A., Howard, J., and Baulcombe, D. (2017) Endogeneous miRNA in the green alga Chlamydomonasregulate translation repression through CDS-targeting.  Nature Plants. Oct; 3(10):787-794 DOI:10.1038/s41477-017-0024-6 October issue with an accompanying News and Views highlight 

First demonstration of the global effects and targeting efficacy of endogenous miRNA on gene expression in plants.

  • Valli, A., Santos, B., Hnatova, S., Bassett, A., Molnar, A., Chung, B., and Baulcombe, D. (2016) Most microRNAs in the single-cell alga Chlamydomonas reinhardtiiare produced by Dicer like 3- mediated cleavage of introns and untranslatable regions of coding RNAs. Genome Research26(4): 519-529, DOI: 10.1101/gr.199703.115 
  • Irigoyen, N., Firth, A., Jones, J., Chung, B., Siddell, S., and Brierley, I. (2016) High-resolution analysis of Coronavirus gene expression through RNA sequencing and ribosome profiling. PLoS Path.12(2):e1005473. DOI: 10.1371/journal.ppat.1005473
  • Chung, B. (co-corresponding author), Hardcastle, T., Jones, J., Irigoyen, N., Firth, A., Baulcombe, D., and Brierley, I. (2015) The use of duplex-specific nuclease in ribosome profiling and a user-friendly software package for Ribo-Seq data analysis. RNA, 21: 1731-1745DOI: 10.1261/rna.052548.115

Development of a non-organism specific rRNA depletion method for ribosome profiling and a software package for simultaneous analysis of ribosome profiling and corresponding RNA-seq.

  • Olspert, A., Chung, B., Carr, J., and Firth, A. (2015) Transcriptional slippage in the positive-sense RNA virus family Potyviridae. EMBO Rep, 16: 995-1004,with an accompanying News and Views highlight DOI: 10.15252/embr.201540509

Deciphered the non-canonical expression mechanism of P3N-PIPO, an overlapping gene in the largest plant virus family.

  • Smirnova, E., Firth, A., Scheidecker, D., Brault, V., Reinbold, C., Rakotondrafara, A., Chung, B., Miller, W., and Ziegler-Graff, V. (2015) Discovery of a small non-AUG-initiated ORF in Poleroviruses and Luteoviruses that is required for long-distance movement. PLoS Path, 11: e1004868, DOI: 10.1371/journal.ppat.1004868
  • Cook, A., Chung, B. (joint first author), Bass, D., Moureau, G., Mcalister, E., Culverwell, L., Glucksman, E., Wang, H., Brown, T., Gould, E., Harbach, R., De Lamballerie, X. and Firth, A. (2013)Novel virus discovery and genome reconstruction from field RNA samples reveals highly divergent viruses in dipteran hosts. PLoS ONE, 8: e80720, DOI: 10.1371/journal.pone.0080720
  • Kuchibhatla, D., Sherman, W., Chung, B., Cook, S., Schneider, G., Eisenhaber, B. and Karlin, D. (2013) Powerful sequence similarity search methods and in-depth manual analyses identify remote homologs in many apparently “orphan” viral proteins. J Virol88: 10-20, DOI:10.1128/JVI.02595-13
  • Chung, B., Firth, A. and Atkins, J. (2010) Frameshifting in Alphaviruses: a diversity of 3′ stimulatory structures. J Mol Biol, 397: 448-456DOI:10.1016/j.jmb.2010.01.044

Characterization of cis-elements utilized for programmed ribosome frameshifting in Alphaviruses

  • Firth, A., Chung, B. (joint first author), Fleeton, M. and Atkins, J. (2008) Discovery of frameshifting in Alphavirus 6K resolves a 20-year enigma. Virol J, 5: 108, DOI: 10.1186/1743-422X-5-108  

Discovery of the overlapping gene (TF) in the important animal virus Alphavirus genus as well as characterization of its non-canonical expression mechanism via ribosome frameshifting 

  • Chung, B., Miller, W., Atkins, J., and Firth, A. (2008) An overlapping essential gene in the Potyviridae. Proc Natl Acad Sci, 105: 5897-5902, DOI: 10.1073/pnas.0800468105, Selected by Faculty of 1000

Discovery of an essential overlapping gene in the largest plant virus family

  • Chung, B., Simons, C., Firth, A., Brown, C. and Hellens, R. (2006) Effect of 5′ UTR introns on gene expression in Arabidopsis thaliana, BMCGenomics, 7: 120, DOI: 10.1186/1471-2164-7-120