Faculty of Science

Department of Biological Sciences
Ding Jeak Ling

Professor

Contact Information:
Department of Biological Science
National University of Singapore
14 Science Drive 4
Singapore 117543
Tel: 65162776
Fax:67792486 email: dbsdjl@nus.edu.sg

Ph.D.(Royal Postgraduate Medical School,University of London, UK

Research Interest : Innate Immunity & Pathogen surveillance strategies

Our lab studies host-pathogen interaction in infection and immunity. We examine the mechanisms of action of pattern recognition receptors (PRRs) and their interaction partners during acute phase infection. We have discovered new and important functions of several immune-responsive molecules which are evolutionarily conserved ~500 million years from horseshoe crab to human, eg: (i) lectins, complements, proteases, protease inhibitors localized to the plasma, (ii) TLRs on the membrane and (iii) NF-kB, TRX, SARM within the cell. By studying the ensemble of immune-responsive PRRs and what regulates their immediate action during acute infection-inflammation, we have unraveled new cryptic functions for well-known classical proteins like C-reactive protein (a clinical marker for inflammation) and the respiratory proteins, showing how these PRRs crosstalk collaborate to boost pathogen surveillance and immune response.

Besides unraveling fundamental mechanisms of innate immunity, we characterize those PRRs which directly bind bacterial ligands (pathogen-associated molecular patterns, PAMPs). The bioactive domains of the PRRs:PAMP interactions are delineated. Peptides which are derived from LPS-binding proteins become potential probes and prototypes for further development into novel LPS-sensors, antimicrobials and tools for LPS-removal. We have used the peptides to investigate LPS-binding and antimicrobial combat. We have innovated a molecular biosensor for endotoxin for quality assurance of injectables and medical devices. This IP has been commercialized worldwide as PyroGene by Lonza Inc.  

Research Highlights/Accomplishments:

1. 1995 National Science & Technology Award for 'outstanding contributions to genetic engineering'
2. 2000 Far Eastern Economic Review Award for Scientific Innovations
3. 2000 NUS Outstanding Researcher Award
4. 2008 Faculty of Science, NUS Outstanding Researcher Award
5. 2009 Provost Chair Professorship

Recent Representative Publications

  • Du RJ, Ho B & Ding JL. Rapid reprogramming of haemoglobin structure-function exposes multiple dual-antimicrobial potencies. EMBO J. (2009) doi:10.1038/emboj.2009.380   (pdf)

  • Zhang J, Koh JY, Lu JH, Thiel S, Leong BSH, Sethi S, He CYX, Ho B & Ding JL. Local inflammation induces complement crosstalk which amplifies the antimicrobial response. PLoS Pathogens (2009) 5 (1): 1-15. (pdf)

  • Low DHP, Ang ZW, Yuan Q, Frecer V, Ho B, Chen J & Ding JL. A novel human Tectonin protein with multivalent b-propeller folds interacts with ficolin and binds bacterial LPS. PLoS One (2009) 4 (7):e6260, doi:10.1371/journal.pone.006260. (pdf)

  • Leptihn S, Har JY, Chen J, Ho B, Wohland T & Ding JL. Single molecule resolution of the antimicrobial action of quantum dot-labeled sushi peptide on live bacteria. BMC Biol. (2009) 7:22, doi:10.1186/1741-7007-7-22. (pdf)

  • Jiang N, Thangamani S, Chor CF, Wang SY, Winarsih I, Du RJ, Sivaraman J, Ho B & Ding JL. A novel serine protease inhibitor acts as an immunomodulatory switch while maintaining homeostasis. J Innate Immunity(2009) 1 (5): 465-479.(pdf)

  • Ding JL, Gan ST & Ho B (2009) ssDNA oligoaptamers: molecular recognition and LPS-antagonism are length- and secondary structure-dependent. J Innate Immunity 1 (2009):46-58 (pdf)

  • Le Saux A, Ng MLP, Koh JJY, Low DHP, Leong GEL, Ho B & Ding JL. The macromol assembly of PRRs is impelled by serine proteases via their CCP modules. J Mol Biol 377 (2008): 902-913. (pdf)

  • Wang XW, Tan BZ, Sun M, Ho, B and Ding JL. TXNL6 protects retinal cell line from photooxidative damage by upregulating NF-kB activity. Free Rad Biol Med. 45 (2008): 336-344. (pdf)

  • Fan ZH, Wang XW, Lu JH, Ho B & Ding JL. Elucidating the function of an ancient NF-kB p100 homologue, CrRelish, in antibacterial defense. Infection & Immunity 76 (2008): 664-670 (pdf)

  • Li Y, Ng MLP, Ho B & Ding JL. CrOctin is a femal-specific pentraxin that binds microbial phosphoethanolamine and bridges PRRs to the invading bacteria. Eur. J. Immunol. 37 (2007): 3477-3488. (pdf)

  • Jiang N, Tan NS, Ho B & Ding JL. Respiratory proteins generate ROS as an antimicrobial strategy. Nature Immunology, doi. 10.1038/ni1501 (Sept 2007) (pdf)

  • Ng PML, Le Saux A, Lee CM, Tan NS, Lu JH, Thiel S, Ho B & Ding JL. C-reactive protein collaborates with plasma lectins to boost immune response against bacteria. EMBO J. (2007) (online publication doi: 10.1038/sj.emboj.7601762). (pdf)

  • Wang XW, Tan NS, Ho B & Ding JL. Evidence for the ancient origin of the NFkB/IkB cascade - its archaic role in infection and immunity. Proc. Natl. Acad. Sci (USA). 103 (2006): 4204-4209. (pdf)

  • Li P, Sun M, Ho B & Ding JL. The specificity of sushi peptides for endotoxin and anionic phospholipids: potential application of POPG as an adjuvant for anti-LPS strategies. Biochem. Soc. Trans. (London) 34 (2006):270-272. (pdf of paper- Mounted on the Internet with the permission of The Biochemical Society, 2006)

  • Ding JL, Tan KC, Thangamani S, Kusuma N, Seow WK, Hanh BTH, Wang J & Ho B. Spatial and temporal co-ordination of expression of immune response during Pseudomonas infection of horseshoe crab, Carcinoscorpius rotundicauda. Genes & Immunity 6 (2005): 557-574. (pdf)

  • Ong ST, Wang LH, Zhu Y, Ho B & Ding JL. The response of ferritin to LPS and acute phase of Pseudomonas infection. J. Endotoxin Res. 11 (2005): 268-280. (pdf)

  • Tan SSH, Ng PML, Ho B & Ding JL. The antimicrobial properties of C-reactive protein (CRP). J. Endotoxin Res. 11 (2005):249-256. (pdf)

  • Yong Zhu, Saravanan Thangamani, Bow Ho and Jeak Ling Ding, The ancient origin of the complement system. The EMBO Journal (2005) 24, 382-394 (pdf)

  • Li, P., Wohland, T, Ho, B. and Ding JL. Perturbation of LPS micelles by Sushi3 (S3) antimicrobial peptide: the importance of intermolecular disulfide-bond in S3 dimer for binding, disruption and neutralisation of LPS. J. Biol. Chem. 279 (2004): 50150-50156. (pdf)

  • Ng, MLP., Tan, SH., Ho, B. and Ding JL. The C-reactive protein: a predominant LPS-binding acute phase protein responsive to Pseudomonas infection. J. Endotoxin Res. 10 (2004): 163-174. (pdf)

  • Ding, JL, Wang, LH. And Ho, B. Current genome-wide analysis on serine proteases in innnate immunity. Current Genomics 5 (2004): 147-155.

  • Frecer, V. Ho, B. and Ding, JHL. Denovo design of potent antimicrobial peptides. Antimicrobial Agents and Chemotherapy, 48 (2004): 3349-3357.

  • Wang LH, Ho B & Ding J L, Transcriptional regulation of a limulus Factor C: repression of an NF?B motif modulates its responsiveness to bacterial lipopolysaccharide. J. Biol. Chem. 278 (2003): 49428-49437

  • Li AK, Sadasivam M & Ding J L, Receptor-ligand interaction: Vtg receptor and Vtg, implications on LDLR and Apo B/E. The first three ligand binding repeats of Vtg receptor interact with the N-terminal region of Vtg. J. Biol. Chem. 278 (2003): 2799-2806

  • Zhu Y, Ho B & Ding J L, Sequence and structural diversity in endotoxin-binding dodecapeptides. Biochim. Biophys. Acta 1611 (2003): 234-242

  • Li CG, Ng P M L, Zhu Y, Ho B & Ding J L, Tandem repeats of sushi peptide with enhanced LPS-binding and –neutralising activities. Protein Engineering 16 (2003): 629-635

  • Wang J, Tan N S, Ho B & Ding J L, Modular arrangement and secretion of a multidomain serine protease: evidence for involvement of proline-rich region and N-glycans in the secretion pathway. J. Biol. Chem. 277 (2002): 36363-36372

  • Goh YY, Ho B & Ding J L, A novel fluorescent protein-based biosensor for gram-negative bacteria. Appl. Environ. Microbiol. 68 (2002): 6343-6352

  • Goh YY, Frecer V, Ho B & Ding J L, Rational design of green fluorescent protein mutants as biosensor for bacterial endotoxin. Protein Engineering 15 (2002): 493-502

  • Tan N S, Ding J L & Ho B, Engineering a novel secretion signal for cross-host rcombinant protein expression. Protein Engineering 15 (2002): 337-345

  • Ding J L & Ho B, New era in pyrogen testing. Trends in Biotechnology, 19 (2001): 277-281

  • Yau YH, Ho B, Tan N S, Ng P M L & Ding J L, The high therapeutic index of Factor C sushi peptides: potent antimicrobials against Pseudomonas aeruginosa. Antimicrobial Agents Chemotherapy, 45 (2001): 2820-2825

  • Ding J L, Zhu Y & Ho B, High performance affinity capture/removal of bacteiral pyrogen from solutions. J. Chromatography, 795 (2001): 237-246.

  • Tan NS, Ho B & Ding JL (2000) High affinity LPS-binding domain(s) in recombinant Factor C of a horseshoe crab neutralizes LPS-induced lethality. FASEB Journal 14: 859-870.

  • Frecer V, Ho B & Ding JL (2000) Interpretation of biological activity data of bacterial endotoxins by simple molecular models of mechanism of action. Eur. J. Biochem. 267: 837-852.

  • Tan NS, Ho B & Ding JL (2000) Definition of endotoxin-binding sites in horseshoe crab Factor C recombinant sushi proteins and neutralisation of endotoxin by sushi peptides. FASEB Journal 14: 1801-1813.

  • Frecer V, Ho B & Ding JL (2000) Molecular dynamics study of lipid A from E. coli and its monophospho and dephospho analogues. Biochim. Biophys. Acta 1466: 87-104.

 

Patents:

  1. 1998, 1999, 2001, 2002 -Cloning and expression of horseshoe crab Factor C for detection, removal of endotoxin & endotoxin therapeutics (US Patents granted)

  2. 1998 - 2009 Isolated nucleic acids encoding a secretory signal for expression and secretion of heterologous recombinant proteins (US Patent filed).

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