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Department of Pathology

 
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 is centred around the translational control of protein synthesis – an essential biological process in all living organisms. Translational regulation is widespread and especially important in the cellular response to stress factors, growth cues and differentiation signals. After 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.

With support from Long-Term EMBO and Sir Henry Wellcome Postdoctoral Fellowships, I joined the Department of Plant Sciences at the University of Cambridge. There, I elucidated the ancestral mechanism of miRNA-mediated translational regulation using the green algae Chlamydomonas reinhardtii as a model organism. Subsequently, through a Medical Research Council Career Development Fellowship, I established my research group within the Department of Pathology. Our primary focus is on investigating the molecular mechanisms of gene expression and translational control at the host-pathogen interface across various domains of life, particularly in the animal and plant kingdoms, and across multiple pathogen systems including viruses, bacteria, and eukaryotic parasites.

Our recent discoveries include the rapid translational induction of sentinel cells in response to osmotic changes as a mechanism to overcome infection, and the identification of novel translation mechanisms in pathogenic bacteria. My long-term scientific vision is to understand how living organisms utilise novel gene expression mechanisms to respond and adapt to the challenging and complex biosystems we live in, and how we can use these molecular discoveries to engineer biological systems for biotechnological applications to combat pathogen infection in the face of climate change.

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.
 

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Group members:

Dr Sherine Thomas

Ms Arlia Rapaiee

Dr Filip Lastovka

Dr George Wood

Dr Li Yang

Mr Vebushan Sukumar

Dr Sam Crawshaw

Visiting scientist

Dr Mariya Lobanovska (UC Berkeley, Portnoy Lab)

Dr Alex Murphy (Department of Plant Sciences, Carr Lab)

Dr Jessica Bergman (Department of Plant Sciences, Carr Lab)

Dr Andrew Yep (Department of Plant Sciences, Carr Lab)

 

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 2022Chung et al.2015 RNA]

 

Peer reviewed publications

  • Bryant, O*., Lastovka, F*., Powell, J., Chung, B. (2023) The distinct translational landscape of Gram-positive and Gram-negative bacteria. Nature Communications DOI: 10.1101/2023.05.25.542305

         First high-definition ribosome profile of any wild-type bacterial system; Discovery of novel cis-regulatory elements in Gram negative bacteria that drives efficient translation; Discovery of novel translation initiation    mechanism in the Gram positive bacteria Listeria.

  • 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: 1731-1745DOI: 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 

              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

Contact Details

Tennis Court Road, CB21QP
Cambridge, United Kingdom
Office Phone: +44 (0)1223 333331
Lab Phone: +44 (0)1223 333545
Not available for consultancy