Lu Shin Wong
  • Manchester Institute of Biotechnology, 131 Princess Street

    M1 7DN Manchester

    United Kingdom

Personal profile

Biography

Lu Shin Wong graduated with a Bachelor of Pharmacy from the University of Nottingham in 1997. He then practised as a hospital pharmacist for four years while pursuing a postgraduate diploma in clinical pharmacy from the University of Bradford. He subsequently undertook his PhD studies in organic and analytical chemistry at the University of Southampton with Prof. Mark Bradley. Upon completing this in 2005, he joined the Manchester Institute of Biotechnology as a postdoctoral research associate with Prof. Jason Micklefield on the application of chemical biology and surface chemistry to biomolecular-array technologies. In 2008, Lu Shin was awarded an EPSRC Life Science Interface research fellowship, which enabled him to work with Prof. Chad A. Mirkin at the International Institute for Nanotechnology, Northwestern University. In 2011, he returned to the UK and was appointed as a lecturer at the School of Chemistry.

 

Memberships of committees and professional bodies

Member of the Royal Pharmaceutical Society of Great Britain (RPSGB)

Member of the Royal Society for Chemistry (RSC)

Member of the American Chemical Society (ACS)

Overview

Our multidisciplinary research interests lie at the interface between biotechnology and nanotechnology, with an emphasis of chemical molecular methods and approaches. Our work is thus underpinned by components of synthetic chemistry (for the synthesis of building blocks, linkers and enzyme substrates), molecular biology (to enable the genetic engineering of recombinant proteins) and surface chemistry (for the nanofabrication of devices). The research activities in our group are currently divided into:

Biocatalysis. The development of modified recombinant enzymes to enable chemical transformations that are more selective and sustainable.

Nanofabrication. The use of scanning probe methods together with chemical catalytic and biocatalytic methods for surface fabrication.

See the Research and Projects section for more details.

See a video of one of our research highlights on CAMERA's Youtube Channel.

Research interests

Biocatalysis

Enzymes in organosilicon chemistry. Organosiloxanes are components in a huge variety of consumer products and play a major role in the synthesis of fine chemicals. However, their synthetic manipulation primarily relies on the use of chlorosilanes, which are energy-intensive to produce and environmentally undesirable. Synthetic routes that operate under ambient conditions and circumvent the need for chlorinated feedstocks would therefore offer a more sustainable route for producing this class of compounds.

We are investigating the silicateins, a family of enzymes derived from a marine sponge that is able to catalyse the cleavage and formation of silicon-oxygen bonds. This research aims to understand its mechanism of action and to develop the enzyme for applications in the production of silicon-containing materials.

 

Scheme of generic silicon-oxygen bond hydrolysis and condensation, with image of modelled enzyme active site

 

Sustainable oxidations and reductions are key to reducing the environmental impact of a range of chemical processes, from the synthesis of fine chemicals (e.g. pharmaceuticals, agrochemicals), to the breakdown of polymers for recycling.

We are developing the use of enzymes that use readily available and safe oxidants such as hydrogen peroxide and air for chemical synthesis and electrochemical devices. For example, we have demonstrated the use of heterologously produced horseradish peroxidase for the oxidation of electron-rich aromatic molecules to their corresponding quinones, and their subsequent tandem reactions to generate more complex structures.

 

Scheme showing the oxidation of hydroquinoid molecules to their corresponding quinones, and subsequent further synthetic steps to more complex products

 

Biocatalytic immobilisation of proteins on to a variety of materials has wide applications in areas such as the generation of protein arrays and biosensors. In particular we are interested in the approaches that allow covalent and site-specific protein attachment, which will be needed at the nanometre size regime where only a relatively small number of molecules will be immobilised and maximal activity will be crucial.

In collaboration with Jason Micklefield, we have demonstrated the use of the phosphopantetheinyl transferase enzyme Sfp for the immobilisation of recombinant proteins bearing the small genetically encoded ybbR tag on to materials functionalised with coenzyme A. Under mild physiological conditions, Sfp transfers the phosphopantetheinyl group from coenzyme A to the serine residue on the ybbR tag of the target protein, resulting in a site-specific and covalent bond between the protein and bulk support. In cases where cleavable linkers are incorporated between the immobilised protein and the support material, cleavage of the linker enables the recovery of the protein for further analysis.

 

Scheme showing protein immobilisation catalysed by Sfp

 

Selected Publications (For complete list, see publications tab)

  1. S. Y. Tabatabaei Dakhili, S. A. Caslin, A. S. Faponle, P. Quayle, S. P. de Visser, L. S. Wong. Recombinant Silicateins as Model Biocatalysts in Organosiloxane Chemistry. Proc. Natl. Acad. Sci., 2017, 114, E5285. http://doi.org/10.1073/pnas.1613320114

  2. J. Hosford, S. A. Shepherd, J. Micklefield, L. S. Wong. A High-Throughput Assay for Arylamine Halogenation Based on a Peroxidase Mediated Quinone-Amine Coupling with Applications in the Screening of Enzymatic Halogenations. Chem. Eur. J., 2014, 20, 16759. http://doi.org/10.1002/chem.201403953

  3. L. S. Wong, F. Khan, J. Micklefield. Selective Covalent Protein Immobilization: Strategies and Applications. Chem. Rev. 2009, 109, 4025. http://dx.doi.org/10.1021/cr8004668

  4. L. S. Wong, J. L. Thirlway, J. Micklefield. Direct Site-selective Covalent Protein Immobilization Catalyzed by a Phosphopantetheinyl Transferase. J. Am. Chem. Soc. 2008, 130, 12456. http://doi.org/10.1021/ja8030278

Research interests

Nanofabrication

The fusion of “top-down” miniaturisation and “bottom-up” synthesis is a frontier area of nanotechnology research, with many applications in cell biology, molecular electronics and photonics. In this respect we are interested in the application of scanning probe lithographic methods derived from atomic force microscopy (AFM).

Using “soft” nanolithographic methods which are able to operate under ambient conditions such as dip-pen nanolithography (DPN) and polymer pen lithography (PPL), we are able to generate surfaces bearing nanoscale features with a variety of chemical properties. Notably, we use multi-probe methods enable the parallelised fabrication of large areas (many cm2) while maintaining nanoscale resolution.

 

AFM Images of arrays of 16-mercaptohexadecanoic acid nanofeatures on a gold substrate printed by PPL

Epifluorescence image of mesenchymal stem cells cultured on nanoscale grids of 16-mercaptohexadecanoic acid printed on a gold substrate by PPL
 

Selected Publications (For complete list, see publications tab)

  1. J. Hosford, M. Valles, F. W. Krainer, A. Glieder, L. S. Wong. Parallelized biocatalytic scanning probe lithography for the additive fabrication of conjugated polymer structures. Nanoscale 2018, 10, 7185-7193. http://doi.org/10.1039/C8NR01283K

  2. S. Wang, J. Hosford, W. P. Heath, L. S. Wong. Large-Area Scanning Probe Nanolithography Facilitated by Automated Alignment of Probe Arrays. RSC Adv., 2015, 5, 61402. http://doi.org/10.1039/c5ra11967g

  3. S. A. M. Carnally, L. S. Wong. Harnessing Catalysis to Enhance Nanolithography. Nanoscale, 2014, 6, 4998. http://doi.org/10.1039/c4nr00618f

  4. L. R. Giam, M. D. Massich, L. Hao, L. S. Wong, C. C. Mader, C. A. Mirkin. Scanning Probe-Enabled Nanocombinatorics Define the Relationship Between Fibronectin Feature Size and Stem Cell Fate. Proc. Natl. Acad. Sci., 2012, 109, 4377. http://doi.org/10.1073/pnas.1201086109

My group

Expertise related to UN Sustainable Development Goals

In 2015, UN member states agreed to 17 global Sustainable Development Goals (SDGs) to end poverty, protect the planet and ensure prosperity for all. This person’s work contributes towards the following SDG(s):

  • SDG 2 - Zero Hunger
  • SDG 3 - Good Health and Well-being
  • SDG 9 - Industry, Innovation, and Infrastructure
  • SDG 12 - Responsible Consumption and Production
  • SDG 14 - Life Below Water

Education/Academic qualification

Doctor of Philosophy, University of Southampton

Award Date: 19 Sept 2005

Postgraduate Diploma in Clinical Pharamcy, University of Bradford

Award Date: 6 Dec 2001

Bachelor of Pharmacy, University of Nottingham

Award Date: 9 Jul 1997

Research Beacons, Institutes and Platforms

  • Biotechnology
  • Advanced materials
  • Manchester Regenerative Medicine Network
  • Advanced Materials in Medicine
  • Sustainable Futures
  • Manchester Institute of Biotechnology
  • Manchester Environmental Research Institute

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