Dr Betty Chung

Translation control and Protein synthesis

RNA structure and function

host pathogen interaction

Infection and immunity

External stresses (e.g. infection, temperature, pH)

Biography

My research focuses on the dynamics of post-transcriptional control of gene expression. After my undergraduate studies in Biochemistry at the University of Otago, Dunedin, New Zealand I pursued a PhD in Biochemistry at University College Cork, Ireland where I focused on elucidating non-canonical gene expression mechanisms in RNA viruses. During this time, I discovered and characterised novel mechanisms viruses use to generate previously unknown, but essential factors for infection. First, in the potyviruses - the largest family of plant viruses, I discovered and characterised a novel gene expression mechanism that results in the production of an essential viral protein PIPO (Pretty Interesting Potyvirius ORF), required for the virus to travel from cell to cell. Second, I discovered and characterised the TF protein of alphaviruses - a group of clinically important mosquito-transmitted arboviruses - where TF is important for the stability of the virus particles.

Following my studies on unusual protein synthesis mechanisms, and supported by Long-Term EMBO and Sir Henry Wellcome Postdoctoral Fellowships, I joined the Department of Plant Sciences, University of Cambridge, where I worked on deciphering the regulation of protein synthesis in plants, making use of the unicellular green algae Chlamydomonas to reveal the ancestral mechanism of miRNA-mediated translational regulation. Now, through a Medical Research Council Career Development Fellowship, I have established my research group in the Department of Pathology where my group aims to understand how living organisms utilise novel protein synthesis regulatory mechanisms to counteract external stresses, especially during host:pathogen interaction (animal) and in response to temperature fluctuation (plants).

Research

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 several high-throughput technologies, such as ribosome profiling - 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.

chunglab2023.jpg

Group members:

Dr Jessica Powell

Dr Sherine Thomas

Matt Brember

Filip Lastovka

Dominykas Murza

George Wood

Ella Bishop

Visiting Scientists

Dr Ying Tian Deng (Baulcombe Lab, Department of Plant Sciences)

Publications

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 2022; Chung et al.2015 RNA]

Peer reviewed publications

Thomas, S., Balcerowicz, M., Chung, B. (2022) RNA structure mediated thermoregulation: What can we learn from plants? Frontiers in Plant Sciences DOI: 10.3389/fpls.2022.938570
Albarnaz, J., Ren, H.,, Torres, A.A., Shmeleva, E.V., Melo, C.A., Bannister, A.J., Brember, M.P., Chung, B.Y.W., Geoffrey L. Smith G.L. (2021) Viral mimicry of p65/RelA transactivation domain to inhibit NF-κB activation. Nature Microbiology DOI: 10.1038/s41564-021-01004-9
Dumetz, F., Chow, E., Harris, L., Umar, M., Jensen, A., Chung, B., Chan, T., Merrick, C., Kwok, K., (2021) G-quadruplex RNA motifs influence gene expression in the malaria parasite Plasmodium falciparum. Nucleic Acids Research DOI:10.1093/nar/gkab1095
Balcerowicz, M., Di Antonio, M., Chung, B., (2021) Hairpin temperature-dependent FRET. Bio-protocol DOI:10.21769/BioProtoc.3950
Pearce, S., Cipullo, M., Chung, B., Brierley, I., Rorbach, J. (2021) Mitoribosome Profiling from Human Cell Culture: A High Resolution View of Mitochondrial Translation. Methods in Molecular Biology: Mitochondrial Gene Expression. 2192:p183-196 DOI:10.1007/978-1-0716-0834-0_14
Chung, B. (co-corresponding author), Balcerowicz M, Antonio M.D., Jaeger K.E., Geng F., Franaszek K., Marriott P., Brierley I., Firth A.E., Wigge P.A., (2020) An RNA thermoswitch regulates daytime growth in Arabidopsis. Nature Plants, May;6(5):522-532, DOI: 10.1038/s41477-020-0633-3,

May issue with an accompanying News and Views highlight.

Selected for Faculty of 1000.

Hot and highly cited by Thompson Reuter

First case of an eukaryotic RNA thermoswitch that controls protein synthesis

Chung, B. (co-corresponding author), Molnar, A., Deery M., Valli, A., Hardcastle, T., Howard J. and Baulcombe, D. (2019) Distinct roles of Argonaute in the green alga Chlamydomonas reveal an evolutionarily conserved mode of miRNA-mediated gene regulation. Sci. Rep., 9:22091, DOI:10.1038/s41598-019-47415-x

Part II of Chlamydomonas miRNA story – provides an explanation of miRNA CDS targeting and its evolutionary importance.

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: 1731-1745, DOI: 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: 448-456. DOI: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, Genomics, 7: 120, DOI: 10.1186/1471-2164-7-120

Medical Research Council Fellow

Division of Microbiology and Parasitology