Wei Huang BEng MSc PhD

Our research is focused on synthetic biology and single cell Raman biotechnology.

The team aims to establish a novel reprogrammable cellular platform for synthetic biology – SimCells (Simple Cells). A SimCell is a genetically reprogrammable “artificial cellular machine”, originally derived from a natural bacterial cell. Its ‘hardware’ is the ‘shell’ and machinery of a cell; and its ‘software’ is engineered mini-genome encoded specific functions. The optimised shell and mini-genome in SimCells enables them to faithfully dedicate most of their energy and resources to specific functions without interference from unwanted pathways and networks. A SimCell is a non-dividing, biochemically active, designable and smart 'cellular machine', which can be continuously produced from parent cells. This research will transform current synthetic biology based on living cells or cell-free system into artificial cellular machine, which are between living and non-living systems, leveraging advantages of both.

SimCells have been used as novel biosensors for medical diagnosis and therapy, and as miniature factories for green energy.

SimCell diagnosis and therapy. SimCells have been designed as 'live drugs' to treat cancers, and to antimicrobial resistant pathogens.

Lim B, Yin Y, Ye H, Cui Z, Papachristodoulou A, Huang WE. Reprogramming Synthetic Cells for Targeted Cancer Therapy. ACS Synth Biol. 2022 Mar 18;11(3):1349-1360. doi: 10.1021/acssynbio.1c00631. 

Chen XJ, Wang B, Thompson IP, Huang WE. Rational Design and Characterization of Nitric Oxide Biosensors in E. coli Nissle 1917 and Mini SimCells. ACS Synth Biol. 2021 Oct 15;10(10):2566-2578. doi: 10.1021/acssynbio.1c00223.

Fan C, Davison PA, Habgood R, Zeng H, Decker CM, Gesell Salazar M, Lueangwattanapong K, Townley HE, Yang A, Thompson IP, Ye H, Cui Z, Schmidt F, Hunter CN, Huang WE. Chromosome-free bacterial cells are safe and programmable platforms for synthetic biology. Proc Natl Acad Sci U S A. 2020 Mar 24;117(12):6752-6761. doi: 10.1073/pnas.1918859117. 

Chen JX, Steel H, Wu YH, Wang Y, Xu J, Rampley CPN, Thompson IP, Papachristodoulou A, Huang WE. Development of Aspirin-Inducible Biosensors in Escherichia coli and SimCells. Appl Environ Microbiol. 2019 Mar 15;85(6). doi: 10.1128/AEM.02959-18.

Rampley CPN, Davison PA, Qian P, Preston GM, Hunter CN, Thompson IP, Wu LJ, Huang WE. Development of SimCells as a novel chassis for functional biosensors. Sci Rep. 2017 Aug 3;7(1):7261. doi: 10.1038/s41598-017-07391-6. 

SimCells for sustainability. A bio-transformation system can be designed and constructed to produce high-valued compounds from H2O and CO2, mediated by SimCells and powered by electrons and sunlight. 

Song Y, Cartron ML, Jackson PJ, Davison PA, Dickman MJ, Zhu D, Huang WE, Hunter CN. Proteorhodopsin Overproduction Enhances the Long-Term Viability of Escherichia coli. Appl Environ Microbiol. 2019 Dec 13;86(1). doi: 10.1128/AEM.02087-19. 

Davison, P. A.; Tu, W.; Xu, J.; S., D. V.; Thompson, I. P.; Hunter, C. N.; Huang, W. E., Engineering a rhodopsin-based photo-electrosynthetic system in bacteria for CO2 fixation. submitted.

Our group is one of the pioneers on single cell Raman biotechnology, developing Raman-stable isotope probing (Raman-SIP), Raman-fluorescent in-situ hybridisation (Raman-FISH) and Raman activated cell sorting (RACS) system, which can be used to characterise bacterial function and link phenotypes to genotypes at the single cell level. The single cell Raman technology has been licensed to industry for applications.

Single cell Raman biotechnology for cell characterisation and AMR 

Yi X, Song Y, Xu X, Peng D, Wang J, Qie X, Lin K, Yu M, Ge M, Wang Y, Zhang D, Yang Q, Wang M, Huang WE. Development of a Fast Raman-Assisted Antibiotic Susceptibility Test (FRAST) for the Antibiotic Resistance Analysis of Clinical Urine and Blood Samples. Anal Chem. 2021 Mar 30;93(12):5098-5106. doi: 10.1021/acs.analchem.0c04709. 

Hsu CC, Xu J, Brinkhof B, Wang H, Cui Z, Huang WE, Ye H. A single-cell Raman-based platform to identify developmental stages of human pluripotent stem cell-derived neurons. Proc Natl Acad Sci U S A. 2020 Aug 4;117(31):18412-18423. doi: 10.1073/pnas.2001906117. 

Song Y, Cui L, López JÁS, Xu J, Zhu YG, Thompson IP, Huang WE. Raman-Deuterium Isotope Probing for in-situ identification of antimicrobial resistant bacteria in Thames River. Sci Rep. 2017 Nov 30;7(1):16648. doi: 10.1038/s41598-017-16898-x. 

Tao Y, Wang Y, Huang S, Zhu P, Huang WE, Ling J, Xu J. Metabolic-Activity-Based Assessment of Antimicrobial Effects by D₂O-Labeled Single-Cell Raman Microspectroscopy. Anal Chem. 2017 Apr 4;89(7):4108-4115. doi: 10.1021/acs.analchem.6b05051. 

Raman activated cell sorting

Liang P, Liu B, Wang Y, Liu K, Zhao Y, Huang WE, Li B. Isolation and Culture of Single Microbial Cells by Laser Ejection Sorting Technology. Appl Environ Microbiol. 2022 Feb 8;88(3):e0116521. doi: 10.1128/AEM.01165-21. 

Jing X, Gou H, Gong Y, Su X, Xu, Ji Y, Song Y, Thompson IP, Xu J, Huang WE. Raman-activated cell sorting and metagenomic sequencing revealing carbon-fixing bacteria in the ocean. Environ Microbiol. 2018 Jun;20(6):2241-2255. doi: 10.1111/1462-2920.14268. 

Song Y, Kaster AK, Vollmers J, Song Y, Davison PA, Frentrup M, Preston GM, Thompson IP, Murrell JC, Yin H, Hunter CN, Huang WE. Single-cell genomics based on Raman sorting reveals novel carotenoid-containing bacteria in the Red Sea. Microb Biotechnol. 2017 Jan;10(1):125-137. doi: 10.1111/1751-7915.12420. 

McIlvenna D, Huang WE, Davison P, Glidle A, Cooper J, Yin H. Continuous cell sorting in a flow based on single cell resonance Raman spectra. Lab Chip. 2016 Apr 21;16(8):1420-9. doi: 10.1039/c6lc00251j.

Zhang P, Ren L, Zhang X, Shan Y, Wang Y, Ji Y, Yin H, Huang WE, Xu J, Ma B. Raman-activated cell sorting based on dielectrophoretic single-cell trap and release. Anal Chem. 2015 Feb 17;87(4):2282-9. doi: 10.1021/ac503974e.

Wang Y, Ji Y, Wharfe ES, Meadows RS, March P, Goodacre R, Xu J, Huang WE. Raman activated cell ejection for isolation of single cells. Anal Chem. 2013 Nov 19;85(22):10697-701. doi: 10.1021/ac403107p. 

Huang WE, Ward AD, Whiteley AS. Raman tweezers sorting of single microbial cells. Environ Microbiol Rep. 2009 Feb;1(1):44-9. doi: 10.1111/j.1758-2229.2008.00002.x. 

Raman-FISH

Huang WE, Ferguson A, Singer AC, Lawson K, Thompson IP, Kalin RM, Larkin MJ, Bailey MJ, Whiteley AS. Resolving genetic functions within microbial populations: in situ analyses using rRNA and mRNA stable isotope probing coupled with single-cell raman-fluorescence in situ hybridization. Appl Environ Microbiol. 2009 Jan;75(1):234-41. doi: 10.1128/AEM.01861-08. 

Huang WE, Stoecker K, Griffiths R, Newbold L, Daims H, Whiteley AS, Wagner M. Raman-FISH: combining stable-isotope Raman spectroscopy and fluorescence in situ hybridization for the single cell analysis of identity and function. Environ Microbiol. 2007 Aug;9(8):1878-89. doi: 10.1111/j.1462-2920.2007.01352.x.

Raman-SIP (stable isotope probing)

Wang Y, Song Y, Tao Y, Muhamadali H, Goodacre R, Zhou NY, Preston GM, Xu J, Huang WE. Reverse and Multiple Stable Isotope Probing to Study Bacterial Metabolism and Interactions at the Single Cell Level. Anal Chem. 2016 Oct 4;88(19):9443-9450. doi: 10.1021/acs.analchem.6b01602. 

Zhang D, Berry JP, Zhu D, Wang Y, Chen Y, Jiang B, Huang S, Langford H, Li G, Davison PA, Xu J, Aries E, Huang WE. Magnetic nanoparticle-mediated isolation of functional bacteria in a complex microbial community. ISME J. 2015 Mar;9(3):603-14. doi: 10.1038/ismej.2014.161. 

Berry D, Mader E, Lee TK, Woebken D, Wang Y, Zhu D, Palatinszky M, Schintlmeister A, Schmid MC, Hanson BT, Shterzer N, Mizrahi I, Rauch I, Decker T, Bocklitz T, Popp J, Gibson CM, Fowler PW, Huang WE, Wagner M. Tracking heavy water (D2O) incorporation for identifying and sorting active microbial cells. Proc Natl Acad Sci U S A. 2015 Jan 13;112(2):E194-203. doi: 10.1073/pnas.1420406112. 

Li M, Huang WE, Gibson CM, Fowler PW, Jousset A. Stable isotope probing and Raman spectroscopy for monitoring carbon flow in a food chain and revealing metabolic pathway. Anal Chem. 2013 Feb 5;85(3):1642-9. doi: 10.1021/ac302910x. 

Li M, Canniffe DP, Jackson PJ, Davison PA, FitzGerald S, Dickman MJ, Burgess JG, Hunter CN, Huang WE. Rapid resonance Raman microspectroscopy to probe carbon dioxide fixation by single cells in microbial communities. ISME J. 2012 Apr;6(4):875-85. doi: 10.1038/ismej.2011.150. 

Huang WE, Griffiths RI, Thompson IP, Bailey MJ, Whiteley AS. Raman microscopic analysis of single microbial cells. Anal Chem. 2004 Aug 1;76(15):4452-8. doi: 10.1021/ac049753k. 

Other research

Huang WE, Lim B, Hsu CC, Xiong D, Wu W, Yu Y, Jia H, Wang Y, Zeng Y, Ji M, Chang H, Zhang X, Wang H, Cui Z. RT-LAMP for rapid diagnosis of coronavirus SARS-CoV-2. Microb Biotechnol. 2020 Jul;13(4):950-961. doi: 10.1111/1751-7915.13586. 

Ng CK, Putra SL, Kennerley J, Habgood R, Roy RA, Raymond JL, Thompson IP, Huang WE. Genetic engineering biofilms in situ using ultrasound-mediated DNA delivery. Microb Biotechnol. 2021 Jul;14(4):1580-1593. doi: 10.1111/1751-7915.13823. 

Song Y, Hahn T, Thompson IP, Mason TJ, Preston GM, Li G, Paniwnyk L, Huang WE. Ultrasound-mediated DNA transfer for bacteria. Nucleic Acids Res. 2007;35(19):e129. doi: 10.1093/nar/gkm710. 

EPSRC, Fellowship for synthetic biology

PI, £1.0M, 2014-2019

Development of SimCells as building blocks for synthetic biology. EP/M002403/1.

BBSRC

Co-I, £430,764, 2018-2020

Effector gene persistence in bacterial plant pathogens. BB/R009236/1.

BBSRC

Co-I, sLoLa, £3.4M, 2015-2020.

Engineering new capacities for solar energy utilisation in bacteria. BB/M000265/1.

EPSRC

Co-I, £2.36M, 2016-2020.

Liquid Fuel and bioEnergy Supply from CO2 Reduction. EP/N009746/1.

NERC

Co-I, £100,449, 2018-2021.

Seedcorn. NE/S008721/1

A full list of publications can be found https://scholar.google.com/citations?user=8aK7kzkAAAAJ&hl=en 

• Lim B, Yin Y, Ye H, Cui Z, Papachristodoulou A, Huang WE. (2022) Reprogramming Synthetic Cells for Targeted Cancer Therapy. ACS Synthetic Biology 11(3):1349-1360.

• Huang W.E.*, Lim B., Hsu C.C., Xiong D., Wu W., Yu Y., Jia H., Wang Y., Zeng Y., Ji M., Chang H., Zhang X., Wang H., Cui Z. (2020) RT-LAMP for rapid diagnosis of coronavirus SARS-CoV-2. Microbial Biotechnology 13:950-961. 

• Fan C., Davison P.A., Habgood R., Zeng H., Decker C.M., Gesell Salazar M., Lueangwattanapong K., Townley H.E, Yang A., Thompson I.P., Ye H., Cui Z., Schmidt F., Hunter C.N., Huang W.E.* (2020) Chromosome-free bacterial cells are safe and programmable platforms for synthetic biology. Proceedings of the National Academy of Sciences of the United States of America 117:6752-6761.

• Hsu C.C., Xu J., Brinkhofa B., Wang H., Cui Z., Huang W.E.*, Ye H.* (2020) A Single-Cell Raman-based Platform to Identify Developmental Stages of Human Pluripotent Stem Cell-derived Neurons. Proceedings of the National Academy of Sciences of the United States of America 117: 18412-18423.

• Zhang, D., Berry, J.P., Zhu, D., Wang, Y., Chen, Y., Jiang, B., Huang, S., Langford, H., Li, G., Xu, J., Aries, E. and Huang, W.E.* (2015) Isolation and physiological characterisation of an uncultured degrader in a complex microbial community. ISME Journal 9:603-614. 

• Li M, Canniffe D.P., Jackson P.J., Davison P.A., FitzGerald S., Dickman M.J., Burgess J.G., Hunter C.N., Huang W.E.* (2012) Rapid resonance Raman microspectroscopy to probe carbon dioxide fixation by single cells in microbial communities. ISME Journal 6:875-885.

• Huang W.E.*, Ferguson A., Singer A.C., Lawson K., Thompson I.P., Kalin R.M., Larkin M.J., Bailey M.J., Whiteley A.S. (2009) Resolving genetic functions within microbial populations: In situ analyses using rRNA and mRNA stable isotope probing coupled with single-cell Raman-fluorescence in situ hybridization. Applied and Environmental Microbiology 75:234-241.

• Huang W.E., Stoecker K., Griffiths R., Newbold L., Daims H., Whiteley A.S., Wagner M. (2007) Raman-FISH: Combining stable-isotope Raman spectroscopy and fluorescence in situ hybridization for the single cell analysis of identity and function. Environmental Microbiology 9:1878-1889.

• Song Y., Hahn T., Thompson I.P., Mason T.J., Preston G.M., Li G., Paniwnyk L., Huang W.E.* (2007) Ultrasound-mediated DNA transfer for bacteria. Nucleic Acids Research 35:e129.

• Huang W.E.*, Griffiths R.I., Thompson I.P., Bailey M.J., Whiteley A.S. (2004) Raman microscopic analysis of single microbial cells. Analytical Chemistry 76:4452-4458.

*Corresponding author

I am currently open to supervising PhD students on synthetic biology and single cell biology