School of Science
Associate Professor Kumaran has a long-standing interest in developing improved gene delivery and expression systems in mammalian cells. Work in his lab has developed several innovative applications using natural microbial mechanisms. In the 1990s his research adapted the natural homologous recombination mechanism operating in E. coli to develop recombination-based technology for genetic manipulation of very large DNA - a task that was extremely difficult until then. Another research project engineered innocuous E. coli to invade mammalian cells to deliver and express human genes. More recently his team has assembled artificial chromosomes that can be used to maintain and achieve long-term expression of human genes. Together these innovations seek to contribute to the field of gene delivery for the correction of human genetic disease and have led to a number of patents in this area. Associate Professor Kumaran is a member of the School of Science’s Industry Advisory Board, which provides strategic advice to the overall direction of the School. My other role is to drive industry engagement and industry led research on Campus.
- Doctor of Philosophy, University of Melbourne, 2000
Molecular genetics, gene expression
1. Recombineering: DNA engineering using homologous recombination
Recombineering permits genetic engineering of DNA using homologous recombination in E. coli. Because homologous recombination is not dependent on the presence of suitably placed restriction enzyme sites like conventional genetic engineering methods, recombineering permits more complex manipulations and is not limited by the size of the DNA. Using this technique, various changes can be added to very large (>100 kb) DNA sequences including i) point mutations, ii) deletions, iii) insertions, and iv) gene fusions to develop specific cell lines and animal models of human disease. My current research is directed to better understand the action of the recombineering enzymes on various DNA substrates and to advance improved applications using this system.
2. E. coli as a vector for gene delivery into mammalian cells
Intracellular bacteria such as Shigella, Yersinia, and Salmonella, have evolved the capability to enter mammalian cells by invasion to establish pathogenicity. My research has adapted a non-pathogenic E. coli strain to express the Y. pseudotuberculosis invasin gene to deliver high molecular weight DNA up to 200 kb in size into mammalian cells by invasion. A vector capable of delivering such large DNA can include complete genes together with their introns, exons, and regulatory regions to permit more accurate expression of a genetic locus. Efforts are ongoing to improve the gene delivery efficiency of this vector into various mammalian cell types.
3. Artificial chromosome research
Gene therapy requires development of improved vectors for long-term retention and accurate expression of transgenes in cells. Currently available vectors can deliver genes efficiently into cells but provide only short bursts of expression before they become silenced by the host cell. To overcome these limitations my research is developing artificial chromosome vectors. Artificial chromosomes will 1) enable long-term retention of the delivered transgenes by existing as independent chromosomes that segregate faithfully to daughter cells during cell division, 2) provide long-term gene expression by avoiding DNA integration into human chromosomes, which can cause transgene silencing, and 3) provide correct levels and duration of expression because they carry complete genes along with their surrounding sequences that function to provide regulation.
- BTH1802 (Fundamentals of biotechnology)
Bacterial Artificial Chromosomes, 2nd Edition (2015): Methods in Molecular Biology Series, Kumaran Narayanan (Editor), Springer, New York
Chen, Q. and Narayanan, K. (2015). Recombineering linear BACs. In Bacterial Artificial Chromosomes, 2nd Edition: Methods in Molecular Biology Series, Kumaran Narayanan (Editor), Springer, New York
Osahor, A., Deekonda, K., Lee, C.W., Sim, E.U., Radu, A., and Narayanan, K. (2017). Rapid preparation of adherent mammalian cells for basic scanning electron microscopy (SEM) analysis. Analytical Biochemistry534: 46-48
Sim, E.U., Ng, K.L, Lee, C.W and Narayanan, K. (2017). The uS8, uS4, eS31, and uL14 ribosomal protein genes are dysregulated in nasopharyngeal carcinoma cell lines. BioMed Research International 4876954, doi.org/10.1155/2017/4876954
Sim, E.U., Chan, S.L.L., Ng, K.L., Lee, C.W., and Narayanan, K. (2016). Human Ribosomal Proteins RPeL27, RPeL43 and RPeL41 are Up-regulated in Nasopharyngeal Carcinoma Cell Lines. Disease Markers. 2016:5179594. doi: 10.1155/2016/5179594.
Sim, E.U., Ma, X, Chan, S.L., Lee, C.W, Narayanan, K. (2016) Predicted interaction of human Ribosomal Protein S15 with Fragile X Mental Retardation Protein. J. App. Biol. & Biotechnology 4: 38-45.
Hui, Y.W., Narayanan, K., and Dykes, G.A. (2015). Control of Attachment of Pseudomonas aeruginosa and Burkholderia cepacia to Surfaces by Shear Force. Water Environ. Res. 88: 2040-2046, doi:10.2175/106143016X14504669767292
Lee, S.W., Lee, C.W., Bong, C.W., Narayanan, K., and Sim, UE (2015). The dynamics of attached and free-living bacterial population in tropical coastal waters. Marine and Freshwater Research. http://dx.doi.org/10.1071/MF14123
Osahor, A.N., Tan, C.Y., Sim, E.U., Lee, C.W., and Narayanan, K. (2014). Short homologies efficiently generate detectable homologous recombination events. Analytical Biochemistry 462: 26-8. doi: 10.1016/j.ab.2014.05.030.
Chen, Q., Lee, C.W., Sim, E.U, and Narayanan, K. (2014) Induction of protein expression within E. coli bactofection vector for entry into mammalian cells. Human Gene Therapy Methods 25: 40-7.
Narayanan, K., Sim, E.U, Lee, C.W., Radu, A. (2013). E. coli bactofection using Lipofectamine. Analytical Biochemistry 439:142-4.
Chen, Q. and Narayanan, K. (2011). Crude protein extraction protocol for phage N15 protelomerase in vitro enzymatic assays. Analytical Biochemistry, 414: 169-171.
Narayanan, K., and Chen, Q. (2011). Bacterial artificial chromosome mutagenesis using recombineering. J. Biomedicine and Biotechnology, 971296, doi:10.1155/2011/971296
Lee, C.W., Ng, A.Y., Bong, C.W., Narayanan, K., Sim, E.U., Ng, C.C. (2011). Investigating the decay rates of Escherichia coli relative to Vibrio parahemolyticus and Salmonella Typhi in tropical coastal waters. Water Research 45:1561-70.
Sim, E.U., Ang, C.H., Ng, C.C., Lee, C.W., and Narayanan, K. (2010). Differential expression of a subset of ribosomal protein genes in cell lines derived from human nasopharyngeal epithelium. J. Human Genetics 55:118-20.
Lee, C.W., Ng, A.Y., Narayanan, K., Sim, E.U., Ng, C.C. (2009). Isolation and characterization of culturable bacteria from tropical coastal waters. Ciencias Marinas 35: 153–167.
Narayanan, K., Sim, E.U, Ravin, N.V., and Lee, C.W. (2009). Recombination between double-stranded DNA substrates in vivo. Analytical Biochemistry 387: 139-141.
Narayanan, K. (2008). Intact recombineering of highly repetitive DNA requires reduced induction of recombination enzymes and improved host viability. Analytical Biochemistry 375: 394-396.
Ooi, Y.S., Warburton, P.E., Ravin, N.V., and Narayanan, K. (2008). Recombineering linear DNA that replicate stably in E. coli. Plasmid 59: 63-71.
Narayanan, K., and Warburton, P.E. (2003). DNA modification and functional delivery into human cells using E. coli DH10B. Nucleic Acids Research 31:e51.
Jamsai, D., Nefedov, M., Narayanan, K., Orford, M., Fucharoen, S., Williamson, R., and Ioannou, P.A. (2003). Insertion of common mutations into the B-globin locus using GET Recombination and an EcoRIendonuclease counter-selection cassette. Journal of Biotechnology 101:1-9.
Narayanan, K., Williamson, R., Zhang, Y., Stewart, A. F., and Ioannou, P.A. (1999). Efficient and precise engineering of a 200 kb Beta-globin human/bacterial artificial chromosome in E. coli DH10B using an inducible homologous recombination system. Gene Therapy 6: 442-447.
Kumaran Narayanan (Project Leader) and Priyia Pusparajah (Monash), 2017, The glycemic index (GI) of SUITENA 178, a naturally-occuring polyol, Fiatec Biactive Sdn Bhd (Industry Grant), RM19k
Kumaran Narayanan (Project Leader)., Sunil K. Lal (Monash), and Emily Goh Joo Kheng (Monash), 2017, Relivium Sciences Sdn Bhd (Industry grant), RM64k
Kumaran Narayanan (Project Leader)., E.U.I., Sim (UNIMAS), Song, B.K. (Monash), 2016, Understanding the Expression Characteristics and Activities of the Phage N15 Protelomerase in Mammalian Cells, Ministry of Higher Education (MoHE) Fundamental Research Grant Scheme (FRGS), RM170k
Khai, N.C (Project Leader)., Lee, W.L., Aditya, A., Narayanan, K. (Researcher), Sidek, H.M, 2015, Attenuating Influenza A Virus Endocytosis By HB-EGF (Heparin-Binding EGF-Like Growth Factor), Ministry of Higher Education (MoHE) Fundamental Research Grant Scheme (FRGS), RM187k
Kumaran Narayanan (Project Leader) and Lee, C.W. (UM), 2015, Advancing E.coli as a Vector for Gene Delivery into Human Cells: Hybrids with DNA/protein delivery reagents and intracellular strategies, Ministry of Science, Technology and Innovation (MOSTI) Malaysia E-Science Fund, RM281k
Edmund Sim U.H. (UNIMAS) and Kumaran Narayanan (Researcher), 2013, Identification and characterisation of the molecular pathways mediated by a subset of human ribosomal protein genes, Ministry of Higher Education (MoHE) Research Acculturation Collaborative Effort (RACE) grant Scheme, RM50k
Kumaran Narayanan (Project Leader) and Lee, C.W. (UM), 2012, Functional expression of bacteriophage N15 protelomerase activity in mammalian cells, Ministry of Higher Education (MoHE) Experimental Research Grant Scheme (ERGS), RM88k
Kumaran Narayanan (Project Leader), 2011, Determining the minimal length of sequence homology between donor and recipient DNA for homologous recombination to occur in E. coli, Ministry of Higher Education (MoHE) Fundamental Research Grant Scheme (FRGS), RM134k
PhD Students (Present)
- Allan Ng Wee Ren
- Rasaq Akinsola Olajide
- Wong Yin Cheng
- Clerance Cheong Su Yee
- Aarthi Ramesh
PhD Students (Completed)
- Chen Qingwen
- Lee Woon Ching
- Felicia Chung
- Erik Hui Yew Woh
- Alviya Sultana
- Liew Pei Sheng
- Liannie Chua
- Andrew Osahor
Masters Student (Completed)
- Ong Poh Teck
Honours Students (Completed)
- Khor Jian Ming
- Ali Mehdi
- Amrita Subramanian
- Bhavini Suraiya
- Kenny Tan Chau Yan
- Tee Hsin Yee
Membership in Academic Editorial Committees
- Journal reviewer
- Nature Communications
- Nucleic Acids Research
- Molecular Pharmaceutics
- Gene Therapy
- International Journal of Nanomedicine
- Toxicology and Applied Pharmacology
- Journal of Biotechnology
- Analytical Biochemistry
- Molecular Biotechnology
- Journal of Gene Medicine
Engagement with premier Public Universities
Icahn School of Medicine at Mount Sinai, NY, Adjunct Assistant Professor
- Pro Vice Chancellor’s Award for Excellence in Administration, Monash University Malaysia
- Pro Vice Chancellor’s Award for Excellence in Research, Monash University Malaysia