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Sim Tiow Suan BSc (Hons), PhD
Associate Professor
Assistant Dean, Yong Loo Lin School of Medicine, NUS,
Tel: +65 6516 3280
Email: micsimts@nus.edu.sg |
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Approaches to anti-malarial drug discovery research
Malaria, an age-old disease, affects millions of people worldwide including tropical Asia (WHO, 2005). With this widespread disease and the increasing occurrence of drug-resistant Plasmodium falciparum, new therapies requiring the identification of unique targets for drug development are warranted. A vital strategy in drug development is to apply rational drug designs through knowledge of the structural and active sites of drug targets. Using in silico approaches (sequence analysis and homology modelling), validation by site-directed mutagenesis and functional analyses, strategic amino acid residues in selected malarial proteins can be identified.
We are interested in the molecular basis of anti-malarial targets for setting up screens against a collection of natural and biotransformed products. Our studies so far have included primary metabolic genes and genes involved in the parasite’s life cycle: HSP90s, kinases, cysteine proteases.
Gene structure and function analysis: directed modification for improving antibiotic efficacies
The possibility of improving enzymes for the biosynthesis and biotransformation of antibiotics remains a useful challenge for drug development. Isopenicillin N synthase (IPNS) and deacetoxycephalosporin C synthase (DAOCS) have been studied and have provided promising avenues to upgrade industrially important enzymes. Genetically engineered DAOCS has been shown to expand the efficacy of penicillinase resistant β-lactam antibiotics.
Environmental microbiology : monitoring and endorsing microbial water quality
To support microbiological assessment of wastewater and potable water treatment systems, we have set-up a battery of tests, including standard bacteriological tests, coliphage evaluation, parasite detection, toxicity tests and PCR amplification of signature sequences for species identification. |
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Goo KS, Chua CS, Sim TS (2008) Relevant double mutations in bioengineered Streptomyces clavuligerus deacetoxycephalosporin C synthase result in higher binding specificities which improve penicillin bioconversion. Appl. Environ. Microbiol. 74:1167-1175
Chua CS, Biermann D, Goo KS and Sim TS (2007) Elucidation of active site residues of Arabidopsis thaliana flavonol synthase provides a molecular platform for engineering flavonols. Phytochemistry. 69:66-75
Goo KS, Chua CS and Sim TS (2008) A complete library of amino acid alterations at R306 in Streptomyces clavuligerus deacetoxycephalosporin C synthase demonstrates its structural role in the ring-expansion activity. Proteins: Structure, Function, and Bioinformatics. 70: 739-747
Low H, Lye YM and Sim TS (2007) Pfnek3 functions as an atypical MAPKK in Plasmodium falciparum. Biochem. Biophys. Res. Commun. 361:439-444
Chan M, Tan DSH and Sim TS (2007) Plasmodium falciparum pyruvate kinase as a novel target for antimalarial drug-screening. Travel Med. Infect. Dis. 5:125-131 Elsevier.
Lye YM, Chan M and Sim TS (2006) Pfnek3: an atypical activator of a MAP kinase in Plasmodium falciparum. FEBS Lett. 580:6083-6092 Elsevier.
Chan M, Tan DSH, Wong SH and Sim TS (2006) A relevant in vitro eukaryotic live-cell system for the evaluation of plasmodial protein localization. Biochimie. 88:1367-1375 Elsevier.
Goh SL, Goh LL and Sim TS (2005) Cysteine protease falcipain 1 in Plasmodium falciparum is biochemically distinct from its isozymes. Parasitol. Res. 97:295-301
Goh LL and Sim TS (2005) Characterization of amino acid variation at strategic positions in parasite and human proteases for selective inhibition of falcipains in Plasmodium falciparum. Biochem. Biophys. Res. Commun. 335:762-770
Chan C, Goh LL and Sim TS (2005) Differences in biochemical properties of the Plasmodial falcipain-2 and berghepain-2 orthologues: Implications for in vivo screens of inhibitors. FEMS Microbiol. Lett. 249:315-321
Goh LL and Sim TS (2004) Homology modelling and mutagenesis analyses of Plasmodium falciparum falcipain 2A: implications for rational drug design. Biochem. Biophys. Res. Commun. 323:565-572 |
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