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Health Sciences profile

Dr Chun Shen Lim

PositionResearch Fellow
DepartmentDepartment of Biochemistry
Research summaryGenomics and bioinformatics

Research

The regulation of gene expression is critical for the normal cellular function and the development of multicellular eukaryotes. It is also important in prokaryotes and virus-infected cells.

I am establishing my research into the fundamental steps of gene expression and how these can be manipulated in experimental systems. I have been researching different aspects of gene expression and regulation since my doctoral (2015-2018) and postdoctoral research (2018-2020).

For more details, see our homepage.

Why are some genes highly expressed? Why are some proteins poorly soluble? We are investigating the key sequence features that control gene expression and protein solubility.

How does the exon-intron gene structure emerge? Most of our genes are in pieces. The existence of the intervening sequences, so called introns, is still a mystery. We are comparing the genomes of various species to probe the origin of introns and their functions.

A new role of introns? We have recently found an undescribed mechanism that regulates gene expression, through splicing and translation. This links splicing and translation, key sequential cellular processes that occur in two separate cellular compartments. We estimate that ~30% of messenger RNAs are regulated by this new mechanism. We are developing computational and experimental methods (e.g., quantitative proteomics) to study this new mechanism.

What is the role of RNA splicing in viruses? Hepatitis B virus (HBV) affect 296million people worldwide. HBV is an unusual DNA virus. HBV produces the pregenomic RNA that is retro-transcribed into genomic DNA. While the introns of most human mRNAs are completely spliced out, the introns of HBV pregenomic RNA are partially spliced. We are investigating the sequence features and cellular processes that control splicing in HBV.

Publications

Bhandari, B. K., Lim, C. S., Remus, D. M., Chen, A., van Dolleweerd, C., & Gardner, P. P. (2021). Analysis of 11,430 recombinant protein production experiments reveals that protein yield is tunable by synonymous codon changes of translation initiation sites. PLoS Computational Biology, 17(10), e1009461. doi: 10.1371/journal.pcbi.1009461

Lim, C. S., Weinstein, B. N., Roy, S. W., & Brown, C. M. (2021). Analysis of fungal genomes reveals commonalities of intron gain or loss and functions in intron-poor species. Molecular Biology & Evolution, 38(10), 4166-4186. doi: 10.1093/molbev/msab094

Bhandari, B. K., Lim, C. S., & Gardner, P. P. (2021). TISIGNER.com: Web services for improving recombinant protein production. Nucleic Acids Research, 49, W654-W661. doi: 10.1093/nar/gkab175

Lim, C. S., Sozzi, V., Littlejohn, M., Yuen, L. K. W., Warner, N., Betz-Stablein, B., … Brown, C. M. (2021). Quantitative analysis of the splice variants expressed by the major hepatitis B virus genotypes. Microbial Genomics, 7, 000492. doi: 10.1099/mgen.0.000492

Chapman, L. M., Spies, N., Pai, P., Lim, C. S., Carroll, A., Narzisi, G., … Zook, J. M. (2020). A crowdsourced set of curated structural variants for the human genome. PLoS Computational Biology, 16(6), e1007933. doi: 10.1371/journal.pcbi.1007933

Bhandari, B. K., Lim, C. S., & Gardner, P. P. (2021). TISIGNER.com: Web services for improving recombinant protein production. Nucleic Acids Research, 49, W654-W661. doi: 10.1093/nar/gkab175

Journal - Research Article

Bhandari, B. K., Lim, C. S., Remus, D. M., Chen, A., van Dolleweerd, C., & Gardner, P. P. (2021). Analysis of 11,430 recombinant protein production experiments reveals that protein yield is tunable by synonymous codon changes of translation initiation sites. PLoS Computational Biology, 17(10), e1009461. doi: 10.1371/journal.pcbi.1009461

Journal - Research Article

Lim, C. S., Sozzi, V., Littlejohn, M., Yuen, L. K. W., Warner, N., Betz-Stablein, B., … Brown, C. M. (2021). Quantitative analysis of the splice variants expressed by the major hepatitis B virus genotypes. Microbial Genomics, 7, 000492. doi: 10.1099/mgen.0.000492

Journal - Research Article

Lim, C. S., Weinstein, B. N., Roy, S. W., & Brown, C. M. (2021). Analysis of fungal genomes reveals commonalities of intron gain or loss and functions in intron-poor species. Molecular Biology & Evolution, 38(10), 4166-4186. doi: 10.1093/molbev/msab094

Journal - Research Article

Bhandari, B. K., Gardner, P. P., & Lim, C. S. (2020). Solubility-Weighted Index: Fast and accurate prediction of protein solubility. Bioinformatics, 36(18), 4691-4698. doi: 10.1093/bioinformatics/btaa578

Journal - Research Article

Chapman, L. M., Spies, N., Pai, P., Lim, C. S., Carroll, A., Narzisi, G., … Zook, J. M. (2020). A crowdsourced set of curated structural variants for the human genome. PLoS Computational Biology, 16(6), e1007933. doi: 10.1371/journal.pcbi.1007933

Journal - Research Article

Tan, L. P., Tan, G. W., Sivanesan, V. M., Goh, S. L., Ng, X. J., Lim, C. S., … the Malaysian Nasopharyngeal Carcinoma Study Group. (2020). Systematic comparison of plasma EBV DNA, anti-EBV antibodies and miRNA levels for early detection and prognosis of Nasopharyngeal Carcinoma. International Journal of Cancer, 146, 2336-2347. doi: 10.1002/ijc.32656

Journal - Research Article

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, 46(9), 4575-4591. doi: 10.1093/nar/gky282

Journal - Research Article

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

Journal - Research Article

Lim, C. S., Goh, S. L., Kariapper, L., Krishnan, G., Lim, Y.-Y., & Ng, C. C. (2015). Inclusion bodies of recombinant Epstein–Barr virus capsid antigen p18 as potential immobilized antigens in enzyme immunoassays for detection of nasopharyngeal carcinoma. Clinica Chimica Acta, 448, 206-210. doi: 10.1016/j.cca.2015.07.008

Journal - Research Article

Lim, K.-S., Tan, A.-H., Lim, C.-S., Chua, K.-H., Lee, P.-C., Ramli, N., … Ng, C.-C. (2015). R54C mutation of NOTCH3 gene in the first Rungus family with CADASIL. PLoS ONE, 10(8), e0135470. doi: 10.1371/ journal.pone.0135470

Journal - Research Article

Lim, C. S., Goh, S. L., Krishnan, G., & Ng, C. C. (2014). Recombinant production of Epstein-Barr virus BZLF1 trans-activator and characterization of its DNA-binding specificity. Protein Expression & Purification, 95, 8-12. doi: 10.1016/j.pep.2013.11.007

Journal - Research Article

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

Journal - Research Other

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

Journal - Research Other

Lim, C. S., Krishnan, G., Sam, C. K., & Ng, C. C. (2013). On optimizing the blocking step of indirect enzyme-linked immunosorbent assay for Epstein-Barr virus serology [Short communication]. Clinica Chimica Acta, 415, 158-161. doi: 10.1016/j.cca.2012.08.031

Journal - Research Other

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