Associate Professor CHNG Shu Sin
(Assistant Head - Research & Education)
B.Sc. (Hons), National University of Singapore, 2000-2003; Ph.D., Harvard University, 2004-2010; Postdoctoral fellow, Harvard Medical School, 2010-2011.
Tel: (65)-6516-2682 | Fax: (65)-6779-1691
Email: email@example.com | CV
Recognition and Achievements
My group focuses on understanding how biological membranes are assembled in cells using bacterial outer membranes as models. Specifically, we are interested to elucidate the mechanisms of inter-membrane lipid trafficking in Gram-negative bacteria and mycobacteria and to identify protein targets in these bacteria for antibiotics discovery.
A postdoctoral position is available in my group from 1st February 2020, which you can check it out here.
[Ref: Yeow, J.; et al, J. Biol. Chem. 2018]
A distinctive feature of the Gram-negative bacterial cell envelope is the asymmetric outer membrane (OM), where lipopolysaccharides and phospholipids (PLs) reside in the outer and inner leaflets, respectively. This unique lipid asymmetry renders the OM impermeable to external insults, including antibiotics and bile salts. In Escherichia coli, the complex comprising osmoporin OmpC and the OM lipoprotein MlaA is believed to maintain lipid asymmetry by removing mislocalized PLs from the outer leaflet of the OM. How this complex performs this function is unknown. Here, we defined the molecular architecture of the OmpC-MlaA complex to gain insights into its role in PL transport. Using in vivo photo-cross-linking and molecular dynamics simulations, we established that MlaA interacts extensively with OmpC and is located entirely within the lipid bilayer. In addition, MlaA forms a hydrophilic channel, likely enabling PL translocation across the OM. We further showed that flexibility in a hairpin loop adjacent to the channel is critical in modulating MlaA activity. Finally, we demonstrated that OmpC plays a functional role in maintaining OM lipid asymmetry together with MlaA. Our work offers glimpses into how the OmpC-MlaA complex transports PLs across the OM and has important implications for future antibacterial drug development.
- CM3225 Biomolecules
- CM4227 Chemical Biology
- Shrivastava, R.; Chng, S.-S., Lipid trafficking across the Gram-negative cell envelope. J. Biol. Chem. 2019, in press. (invited review)
- Ercan, B.; Low, W.-Y.; Liu, X.; Chng, S.-S., Characterization of interactions and phospholipid transfer between substrate binding proteins of the OmpC-Mla system. Biochemistry 2019, 58:114-119.(invited contribution as part of "Future of Biochemistry: The International Issue" (Jan 2019)).
- Yeow, J.; Tan, K. W.; Holdbrook, D. A.; Chong, Z. S.; Marzinek, J. K.; Bond, P. J.; Chng, S.-S., The architecture of the OmpC-MlaA complex sheds light on the maintenance of outer membrane lipid asymmetry in Escherichia coli. J. Biol. Chem. 2018, 293(29), 11325-11340.
- Shrivastava, R.; Jiang, X. E.; Chng, S.-S., Bacterial outer membrane homeostasis via retrograde phospholipid transport in Escherichia coli. Mol. Microbiol. 2017, 106(3), 395-408.
- Xu, Z. J.; Meshcheryakov, V. A.; Poce, G.; Chng, S.-S., MmpL3 is the flippase for mycolic acids in mycobacteria.Proc. Natl. Acad. Sci. U.S.A. 2017, 114(30), 7993-7998.
- Thong, S. H.; Ercan, B.; Torta, F.; Fong, Z. Y.; Wong, H. Y.; Wenk, M.R.; Chng, S.-S., Defining key roles for auxiliary proteins in an ABC transporter that maintains bacterial outer membrane lipid asymmetry. eLife 2016, 5 , e19042.
- Chong, Z.-S.; Woo, W.-F.; Chng, S.-S., Osmoporin OmpC forms a complex with MlaA to maintain outer membrane lipid asymmetry in Escherichia coli. Mol. Microbiol. 2015, 98, 1133-1146.