个人简介

1996 BSc(Eng) and 1999 MSc(Eng) Tianjin University, China 2004 Ph.D. University of Frankfurt, Germany 2005-2008 Postdoc, University of Oxford, UK

研究领域

Biochemistry/Biophysics/Application of Proteins in Biotechnology/Functional Mechanism of Membrane Protein Pores/Channels and Transporters

Engineering protein pores for biosensing: Engineered protein pores can be used as stochastic sensors for single-molecule detection (Fig. 1). The ionic current flowing through a pore under an applied potential is altered when an analyte binds within the lumen. The frequency of the binding events allows the determination of the concentration of an analyte, while the nature of the events (e.g. their amplitude or duration) enables analyte identification. Compare to other approaches, the stochastic sensing has an advantage of being sensitive (nanomolar concentrations), fast (up to microsecond resolution), and without delays from mixing and diffusion (real-time). A quiet outer membrane protein G (qOmpG) from E. coli is a good candidate for use as sensor elements due to its monomeric feature. My research focus on the development of the utility of qOmpG in the following respects: i: to enlarge the spectrum of molecules sensed by qOmpG, the properties of the pore will be tailored by site-direct mutagenesis. Different molecular adapters, which bind to the pore lumen and provide a binding site for analytes will be selected for the detection of variant analytes. ii: to use the qOmpG sensor for the detection of biological macromolecules, such as proteins and DNA. iii: to couple an enzyme to the qOmpG to study the single-molecular enzymatic reaction iv: to use qOmpG pore as a model system with which to gain insights into important biological processes such as transmembrane polymer translocation (e.g. DNA, polysaccharides) or nutrient uptake (e.g. sugars, amino acids).

近期论文

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Fahie M, Romano FB, Chisholm C, Heuck AP, Zbinden M and Chen M: A non-classical assembly pathway of Escherichia coli pore forming toxin cytolysin A. J Biol Chem, 2013, 288(43):31042-51. Zhuang T, Chisholm C, Chen M and Tamm LK: NMR-based conformational ensembles explain pH-gated opening and closing of OmpG channel. J Am Chem Soc, 2013, Oct 9;135(40):15101-13. Lou H, Chen M, Black SS, Bushell SR, Ceccarelli M, Mach T, Beis K, Low AS, Bamford VA, Booth I, Bayley H and Naismith JA: Altered antibiotic transport in OmpC mutants isolated from a series of clinical strains of multi-drug resistant E. coli. PLoS One. 2011, 6(10):e25825. Chen M, Li Q-H and Bayley, H: Orientation of the monomeric porin OmpG in planar lipid bilayers. ChemBioChem 2008 9(18):3029-36. Hwang W, Chen M, Cronin B, Holden M and Bayley, H: Asymmetric droplet interface bilayers. J Am Chem Soc 2008 130: 5878-5879 Chen M, Khalid S, Sansom M and Bayley H: Outer membrane protein G: engineering a quiet pore for biosensing. Proc Natl Acad Sci U S A 2008, 105: 6272-6277 (cover article). Comment in: Eisenberg B: Engineering channels: atomic biology. Proc Natl Acad Sci U S A 2008 Apr 29;105:6211-2. Chen M, Abele R and Tampé R: Functional non-equivalence of ABC signature motifs in the transporter associated with antigen processing. J Biol Chem 2004, 279:46073-46081. Chen M, Abele R and Tampé R: Peptides induce ATP hydrolysis at both subunits of the transporter associated with antigen processing. J Biol Chem 2003, 278:29686-29692. Janas E, Hofacker M, Chen M, Gompf S, van der Does C and Tampé R: The ATP hydrolysis cycle of the nucleotide-binding domain of the mitochondrial ATP-binding cassette transporter Mdl1p. J Biol Chem 2003, 278:26862-26869. Heintke S, Chen M, Ritz U, Lankat-Buttgereit B, Koch J, Abele R, Seliger B and Tampé R: Functional cysteine-less subunits of the transporter associated with antigen processing (TAP1 and TAP2) by de novo gene assembly. FEBS Lett 2003, 533:42-46.