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Sanjay SWARUP (Associate Professor) Deputy Director Singapore-Delft Water Alliance www.sdwa.nus.edu.sg Ph: +65  6516 6852 Fax: +65 6778 0617 Email: dbsss@nus.edu.sg PI, Research Centre of Excellence for Mechanobiology (website)

PhD UF (USA), PhD, Msc IARI, BSc PAU India

The Small Molecule Biology Laboratory

Our research program involves understanding the biological role of small biomolecules. We work in two broad areas involving small molecules. First, to understand metabolic networks- including their modularity, connectivity, control mechanisms and to discover new products or pathways of applied value. Second, to understand the role of cyclic nucleotide 2^nd messengers that control diverse pathways in model bacterial species Pseudomonas or in environmental bacterial communities.

In the metabolic networks program, we have adopted mostly a data-driven systems approach to understand cellular responses to perturbations caused by diverse intrinsic or extrinsic signals in the biological system(s). We combine both wet and dry laboratory work within our group. Our model organisms are diverse and include bacteria (Bacillus, Pseudomonas), Arabidopsis, rat and human skin cells. We have developed capabilities to comprehensively map out the changes in the metabolic complement or the 'metabolome' of cells in response to perturbations such as metabolic mutations, effector molecules, or environmental stresses. This approach has allowed us in various projects to:

• Uncover some broad connections in metabolic networks;
• Describe novel catabolic pathway in bacteria;
• Identify members of novel family of bioactive compounds;
• Propose a 'rhizosphere engineering' approach to increase competitiveness of soil microbes;
• Identify intra- and inter-pathway regulatory controls associated with the 'metabolome'. 

In the signalling program, we have recently described the regulatory mechanism for a novel cyclic nucleotide 2^nd messenger in microbes, cyclic diguanylate. The motility regulator MorA is especially conserved in Pseudomonas, modulates the intracellular messenger levels and controls pathways such as motility and biofilm formation. Current efforts in the laboratory are focused on the elucidation of the structure, function and regulatory circuit of the pathways.

In 2008, we have started applying our fundamental studies to addresses the role of plant-microbial interactions in urban freshwater ecology. This work is being carried out under the umbrella of Singapore-Delft Water Alliance (www.sdwa.nus.edu.sg) and funded by the National Research Foundation. We are taking a taking a multidisciplinary approach incorporating hydraulics, genomics, metabolomics, computational and graphical modelling, and high-resolution imaging to study mechanisms that govern biofilm formation and plant metabolic processes in urban freshwater conditions. Both, single-species (Pseudomonas sp.) model and bacterial communities in aquatic environments are being investigated. We focus on biofilm processes such as bacterial signaling that affect bacterial motility, adhesion, biofilm initiation and metabolic networks including roles of metabolites as nutrients and signals in microbial communities.

Since 2009, we have begun complementary studies at a fundamental level to understand the mechanical properties of motility and biofilm formation in bacteria in relation to their control mechanisms. We are especially interested in understanding the coordinated control of multiple appendages of bacteria such as flagella and pili, taking Pseudomonas as our biological model. This work is being carried out at the Research Centre of Excellence in Mechanobiology (www.dbs.nus.edu.sg/mechano) funded by the National Research Foundation.

Selected Publications (2000-2009)

• Ravichandran, A., Sugiyama, N., Tomita, M., Ishihama, Y., Swarup, S. Ser/Thr/Tyr Phosphoproteome Analysis of Pathogenic and Non-Pathogenic Pseudomonas Species. Proteomics 2009, 9, 1-12

• Ananda Kumar C. S. & S. B. Benaka Prasad & K. Vinaya & S. Chandrappa & N. R. Thimmegowda & S. R. Ranganatha & Sanjay Swarup & K. S. Rangappa (2008) Synthesis and antiproliferative activity of substituted diazaspiro hydantoins: a structure-activity relationship study. Invest New Drugs (2009) 27:131-139

• C.S. Ananda Kumar, S.B. Benaka Prasad, K. Vinaya, S. Chandrappa, N.R. Thimmegowda, Y.C. Sunil Kumar, Sanjay Swarup, K.S. Rangappa , Synthesis and in vitro antiproliferative activity of novel 1-benzhydrylpiperazine derivatives against human cancer cell lines European Journal of Medicinal Chemistry 44 (2009) 1223-1229

• Salekoppal Boregowda Benaka Prasada, Mallappanahally Kambappa Vinaya, Channapille Koppal Siddegowda Ananda Kumar, Sanjay Swarup and Kanchugarakoppal Subbegowda Rangappa, Synthesis and In Vitro Antiproliferative Activity of Diphenyl(piperidin-4-yl)thioamide Methanol Derivatives Letters in Drug Design & Discovery, 2008, 5, 423-430 423

• Stuart Meier, Chris Gehring, Cameron Ross MacPherson, Mandeep Kaur, Monique Maqungo, Sheela Reuben, Samson Muyanga, Ming-Der Shih, Fu-Jin Wei, Samart Wanchana, Ramil Mauleon, Aleksandar Radovanovic, Richard Bruskiewich, Tsuyoshi Tanaka, Bijayalaxmi Mohanty, Takeshi Itoh, Rod Wing, Takashi Gojobori, Takuji Sasaki, Sanjay Swarup, Yue-ie Hsing and Vladimir B. Bajic.  The promoter signatures in rice LEA genes can be used to build a co-expressing LEA gene network. Rice, 1(2):177-187 (2008). [Open access article] Inaugural year, no impact factor

• Parab. G, Rao. R, Lakshminarayanan. S, Von Bing. Y, Moochhala. S.M, Swarup. S. Data driven optimization of metabolomics methods using rat liver samples. Analytical Chemistry (Published online: January 13, 2009 )( DOI: 10.1021/ac801645t)  Impact factor: 5.3

• Choy, W. K. , Bajic, V. B., Heng, M.-W., Veronika, M. and Swarup, S. (2008) Regulatory Networks of Genes Affected by MorA, A Global Regulator Containing GGDEF and EAL Domains in Pseudomonas Aeruginosa. In: Series on Advances in Bioinformatics and Computational Biology, World Scientific, Vol. 8: Regulatory Genomics. Proceedings of the RECOMB2006 Conference on Gene Regulatory Networks.

• Domadia, P. N.; Bhunia, A.; Sivaraman, J.; Swarup, S.; Dasgupta, D. Berberine Targets Assembly of Escherichia coli Cell Division Protein FtsZ. Biochemistry. 2008 47(10): 3225-3234.

• Domadia, P, S Swarup, A Bhunia, D Dasgupta and J Sivaraman*, "Inhibition of bacterial cell division protein FtsZ by cinnamaldehyde".  Biochemical Pharmacology, 74, no. 6 (2007):      831-840

• Bajic, V.B., Veronika, M., Veladandi, P.S., Meka, A., Heng, M.-K., Rajaraman, K., Pan, H., and Swarup, S. (2005) DPBE: A Text-mining Tool for Integrating Associations between Genetic and Biochemical Entities with Genome Annotation and Biochemical Terms Lists. Plant Physiology. Vol. 138: 1914-1925.

• Adaikkalam, V. and Swarup, S. (2005) Characterization of copABCD operon from a copper-sensitive Pseudomonas putida strain. Canadian J. Microbiol. 51: 209-216.

• Bhalla, R., Narasimhan, K. and Swarup, S. (2005) Review: Metabolomics and its Role in Understanding Cellular Processes in Plants. Plant Cell Reports 24: 562-571.

• Mohanty, B., Krishnan, S.P.T., Swarup, S. and Bajic, V. B. (2005) Detection and Analysis of Motifs in Promoters of Anaerobically Induced Genes of Different Plant Species. Annals of Botany 96: 669-681

• Choy, W.K., Lian Zhou, L., Syn, C.K.C., Zhang, L.-H. and Swarup, S. (2004) MorA defines a new class of regulators affecting flagellar development and biofilm formation in diverse Pseudomonas species. J. Bacteriology, vol 185.186: 7221-7228

• Tamilselvi D, Anand G and Swarup S (2004) A geminivirus AYVV-derived shuttle vector for tobacco BY2 cells. Plant Cell Reports. 23:81-90..

• Syn, K C C, J Mangnuson, M T Kingsley and S Swarup, Characterization of Pseudomonas putida genes responsive to nutrient limitation. (2004) Microbiology 150: 1661-1669

• Narasimhan, K., Basheer, C., Bajic, V.B., and Swarup, S. (2003) Enhancement of Plant-Microbe Interactions Using a Rhizosphere Metabolomics-Driven Approach and Its Application in the Removal of Polychlorinated Biphenyls. Plant Physiology, 132, 146-153.

• Pillai, B. V. S. and Swarup, S. (2002) Elucidation of the flavonoid catabolism pathway in Pseudomonas putida PML2 strain by Comparative Metabolic Profiling. Appl. Environ. Microbiol. 68, 143-151.

• Adaikkalam, V. and Swarup, S. (2002) A chromosomally located copper transport operon, copAR, encoding a putative P1-type ATPase and a Mer-type regulatory protein in Pseudomonas putida. Microbiology, 148, 2857-2867

• Teo, W L L, P P Kumar, C J Goh and S Swarup (2001) The expression of Brostm, a KNOTTED1-like gene, marks the cell type and timing of in vitro shoot induction in Brassica oleracea. Plant Molecular Biology, 46: 567-5

• Cheng, P K, L Prakash and S Swarup (2001) High frequency direct shoot regeneration and continuous production of rapid-cycling Brassica oleracea in vitro. In Vitro Cellular and Developmental Biology (Plant). 37, 592-598

• Low, R K W, A P Prakash, S Swarup, C J Goh and P P Kumar (2001) Lambda exonuclease-based subtractive hybridization approach to isolate differentially expressed genes from leaf cultures of Paulownia kawakamii. Analytical Biochemistry, 295: 240-247.

• Low, R K W, A P Prakash, S Swarup, C J Goh and P P Kumar (2001) A differentially expressed bZIP gene is associated with adventitious shoot regeneration in leaf cultures of Paulownia kawakamii. Plant Cell Reports, 20: 696-700.

• Syn, C S K C and S Swarup (2000) A scalable protocol for the isolation of large-sized genomic DNA within an hour from several bacteria. Analytical Biochemistry, 278: 86-90.

Co-authored Papers

• Reza, M A, S Swarup and R M Kini*, "Gene structures of two functionally diverse prothrombin activators, Trocarin D and coagulation factor X in Tropidechis carinatus snake: gene duplication and recruitment of factor X gene to the venom gland". Journal of Thrombosis Haemostasis, 5 (2007): 117-126. (United States). Publication no. 0352285

• Reza M. A., Le T. N. M., Swarup S. and Kini R. M. Molecular evolution caught in action: gene duplication and evolution of molecular isoforms of prothrombin activators in Pseudonaja textilis (brown snake). Journal of Thrombosis Haemostasis, 4: 1346-1353. 2006

• Reza M. A., Swarup S. and Kini R. M. Gene structures of trocarin D and coagulation factor X, two functionally diverse prothrombin activators from Australian rough scaled snake. Pathophysiology of Haemostasis and Thrombosis 34: 205-208. 2005

• Le, T.N., Reza, M.A., Swarup, S. and Kini, R.M. (2005) Gene duplication of coagulation factor V and origin of venom prothrombin activator in Pseudonaja textilis snake. Thromb. Haemost., 93, 420-429.

• Reza, A., Swarup, S. and Manjunatha, K.R. (2005) Two parallel prothrombin activator systems in Australian rough-scaled snake, Tropidechis carinatus. Structural comparison of venom prothrombin activator with blood coagulation factor X. Thromb. Haemost., 93, 40-47

• Veena S. Rao, Sanjay Swarup, R. Manjunatha Kini (2004) The catalytic subunit of pseutarin C, a group C prothrombin activator from the venom of Pseudonaja textilis, is structurally similar to mammalian blood coagulation factor Xa. Thrombosis and Haemostasis 92: 509-521

• Yobas L, Gui EL, Ji HM, Li J, Chen Y, Hui WC, Rafe SRM, Swarup S, Wong SM, Lim TM, Heng CK (2004) A flow-through shear-type microfilter chip for separating plasma and virus particles from whole blood. Proceedings of the Micro Total Analysis Systems 2004. 2. 2:7-12.

• Veena S. Rao, Sanjay Swarup, and R. Manjunatha Kini (2003) The nonenzymatic subunit of pseutarin C, a prothrombin activator from eastern brown snake (Pseudonaja textilis) venom, shows structural similarity to mammalian coagulation factor V. Blood. 102: 1347-1354

Book Chapters (2000-2004)

• Reuben S, Bhinu VS and Sanjay Swarup (2008) Rhizosphere metabolomics: Methods and Applications, Chapter 3, In: SECONDARY METABOLITES IN SOIL ECOLOGY" Part 1: Springer Berlin Heidelberg, pp 37-68.

• Swarup, S. and Ong, B.L. (2004) Enhanced Food Production and Security of Asian Leafy Vegetables. pages 181-196. In : Food Security and Vegetables- A Global Perspective. Eds. P. Nath, P.G. Gaddagimath, O.P. Datta. Publishers, PNASF, Bangalore, India.

• Hong Pan, Li Zuo, Rajaraman Kanagasabai, Zhuo Zhang, Vidhu Choudhary, Bijayalaxmi Mohanty, Sin Lam Tan, S.P.T. Krishnan, Pardha Sarathi Veladandi, Archana Meka, Weng Keong Choy, Sanjay Swarup, Vladimir B Bajic (2004) Extracting information for meaningful function inference through text-mining. In: 'Discovering Biomolecular Mechanisms with Computational Biology'. Ed. Frank Eisenhaber. Landes Bioscience Publishers. Texas, U.S.A.

• Reuben, S, Cseke, L., Jayakumar, S, Pillai, B.V.S., Narasimhan, K. and Swarup, S. Molecular Biology of Plant Natural Products (Chapter 5). In "Natural Products From Plants", Second Edition. Eds. L. Cseke et al. Boca Raton, FL: CRC Press, 2006. 611 pp.

• Pillai, B.V.S, Narasimhan, K. Swarup, S. Plant Natural Products in the Rhizosphere (Chapter 4). In 'Natural Products from Plants', Second Edition. Eds. L. Cseke et al. 143 164.Boca Raton, FL: CRC Press, 2006. 611 pp.

Bioinformatics Tools

• Microbial Marker Discovery Tool (MMDT): It is a well defined computational pipeline to compare multiple genomes in order to identify polymorphic regions and design primers for microbial diagnostics and other applications.
  [http://plantmiclab.science.nus.edu.sg/MMDT/microbialmarker.html]

• Dragon Metabolome Explorer(DME): It is a system for exploring potential associations in the metabolic networks (pathways, enzymes and metabolites), ontologies (anatomy, developmental stages) and genes in plants, based on mining PubMed documents.
  [http://research.i2r.a-star.edu.sg/DRAGON/ME/]