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Small Molecule Biology Laboratory

We have an interest in understanding the biological role of small molecules. We study their roles in metabolic pathways and as second messengers in signal transduction pathways in the homologous biological systems. In heterologous systems, we study their role as bioactive molecules. The underlying platform includes a combination of analytical technologies such as chromatography coupled with mass spectrometry, functional genomics technologies such as gene microarray and proteomics and integrated with in-house developed computational and bioinformatics tools. Hence, we combine 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 stresses. This approach has allowed us in various projects to (i) uncover some broad connections in metabolic networks; (ii) describe novel microbial catabolic pathway; (iii) identify members of novel family of bioactive compounds; (iv) propose a 'rhizosphere engineering' approach to increase competitiveness of soil microbes and (v) identify groups of co-regulated genes associated with the 'metabolome'. We are currently taking a systems approach to understand metabolic networks and their perturbation by diverse intrinsic or extrinsic signals in plant and animal models.

We have recently described the regulatory mechanism for a novel cyclic nucleotide 2nd messenger in microbes, cyclic-di-GMP. The regulator MorA is especially conserved in Pseudomonas, it synthesizes as well as hydrolyses cyclic-di-GMP and controls more than 150 genes in pathways such as motility and biofilm formation. Another small molecule, acetyl phosphate, acts as a cofactor in this process. Current efforts in the laboratory are focused on the elucidation of the structure, function and regulatory circuit of the pathway.

Selected Publications (2000-2006)

• 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 Aug 1. Vol. 384 (In press).

• 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., 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

• 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

• 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.

• 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

Book Chapters (2000-2004)

•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.

• 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.