CHNG Shu Sin
Associate Professor, Vice Dean (Student Life and Alumni Relations), Associate Director (Singapore Center for Environmental Life Sciences Engineering (SCELSE-NUS))
Postdoc., Harvard Medical School, 2011; Ph.D., Harvard University, 2010; B.Sc.(Hons), National University of Singapore, 2003.
Contact Information:
Office: S9-12-01D
Tel: (65)-6516-2682
Fax: (65)-6779-1691
Email: chmchngs@nus.edu.sg
Research
Recognition and Achievements
Research Interests
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.
Research Highlight
Tuberculosis continues to pose a serious threat to global health. Mycobacterium tuberculosis, the causative agent of tuberculosis, is an intracellular pathogen that relies on various mechanisms to survive and persist within the host. Among their many virulence factors, mycobacteria encode Mce systems. Some of these systems are implicated in lipid uptake, but the molecular basis for Mce function(s) is poorly understood. To gain insights into the composition and architecture of Mce systems, we characterized the putative Mce1 complex involved in fatty acid transport. We show that the Mce1 system in Mycobacterium smegmatis comprises a canonical ATP-binding cassette transporter associated with distinct heterohexameric assemblies of substrate-binding proteins. Furthermore, we establish that the conserved membrane protein Mce1N negatively regulates Mce1 function via a unique mechanism involving blocking transporter assembly. Our work offers a molecular understanding of Mce complexes, sheds light on mycobacterial lipid metabolism and its regulation, and informs future anti-mycobacterial strategies.
[Ref: Chen, Y.; Wang, Y.; Chng, S.-S., Nat. Commun. 2023]
Teaching Contributions
- CM1102 Chemistry – The Central Science
- CM3225 Biomolecules
- CM4227 Chemical Biology
Representative Publications
- Tan, W.B.; Chng, S.-S., How bacteria establish and maintain outer membrane lipid asymmetry. Annu. Rev. Microbiol. 2024, 78, 27.1–27.21. (invited review)
- Yeow, J.; Luo, M.; Chng, S.-S., Molecular mechanism of phospholipid transport at the bacterial outer membrane interface. Nat. Commun. 2023, 14 (1), 8285.
- Chen, Y.; Wang, Y.; Chng, S.-S., A conserved membrane protein negatively regulates Mce1 complexes in mycobacteria. Nat. Commun. 2023, 14 (1), 5897.
- Tan, W.B.; Chng, S.-S., Genetic interaction mapping highlights key roles of the Tol-Pal complex. Mol. Microbiol. 2022, 117 (4), 921-936.
- Low, W.-Y.; Thong, S.H.; Chng, S.-S., ATP disrupts lipid-binding equilibrium to drive retrograde transport critical for bacterial outer membrane asymmetry. Proc. Natl. Acad. Sci. U.S.A. 2021, 118 (50), e2110055118.
- Jiang, X.E.; Tan, W.B.; Shrivastava, R.; Seow, D.C.S.; Chen, S.L.; Guan, X.L.; Chng, S.-S. Mutations in enterobacterial common antigen biosynthesis restore outer membrane barrier function in Escherichia coli. Mol. Microbiol. 2020, 114 (6), 991-1005.
- 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.
