A recent paper by the GibsonGroup has been highlighted in RSC Chemistry World, and also selected as a 'hot' article in Molecular Biosystems. This work, in collaboration with the FullamGroup, describes a new method for identfiying bacteria, by creating 'barcodes' describing how bacteria bind to different sugars. In the work, the team assembled small arrays of simple sugars onto a surface, and then mapped how different bacteria bind to them. This allowed a trianing matrix to be developed, so unknown bacteria could then be identified. The key to this is its simplicity and scalable to a range of different biosensory surfaces. In this preliminary work, a range of Gram Negative and Gram Postive Mycobacteria were tested and identified. This included surrogates for Mycobacterium Tubuculosis. It is hoped that this will translate to easy point of care biosensors, and to enable more effecient use of antibiotics.

Read the paper here.

Discrimination between bacterial species by ratiometric analysis of their carbohydrate binding profile

Our latest paper, in collaboration with the FullamLab (Life Sciences) has been published in Molecular Biosystems. In this work we demonstrate a new, easy, concept to the identification of Bacterial species. Recently, much interest has been placed on identifying bacteria using sequencing techniques - these are excellent, but need a culturing step and bio-film forming species are a problem. They also need signifcant infrastructure, which is a challenging in the developing world. There is also the growing problem of antibiotic resistance in developed countries.

To address this we have profiled how bacteria bind to carbohohydrates (sugars). Using a simple microwell plate, we could type the bacteira based on their profile, in essence creating a barcode. We could then use this to assign blind samples. We hope to translate this to clinically relevant strains, and also to more realistic (and cheap) detection systems.

Read the paper here (open access)

Otten, LC, Fullam, E, Gibson, M.I. Molecular Biosystems, 2016, 'Discrimination between Bacterial Species by Ratiometric Analysis of their Carbohydrate Binding Profile'

Lucienne Otten passed her PhD viva today, examined by Manuella Tosin (internal) and Ed Yates (Liverpool). Her Thesis was entitled 'Pathogen Detection Based on Carbohydrate Adhesion' and funded by the Systems Biology CDT. In short, Lucienne used 'simple' sugars and accesible chemsitry to make arrays which we used to interrogate pathogens (toxins, bacteria, viruses and parasites) and to create mathematical models of how they bound - in essence we made barcodes. USing this we could then use the arrays to rapidly discriminate between different toxins and species.

Read some of Luciennes papers!

Otten, LC, Fullam, E, Gibson, M.I. Molecular Biosystems, 2016, 'Discrimination between Bacterial Species by Ratiometric Analysis of their Carbohydrate Binding Profile' link

Richards, SJ, Otten, LC, Gibson, MI, J. Mater. Chem. B., 2016, Glycosylated Gold Nanoparticle Libraries for Label-Free Multiplexed Lectin Biosensing, Accepted Link

Otten, L.C., Gibson, MI. RSC Advances, 2015, 5, 53911 - 53914,. 'Discrimination between Lectins with Similar Specificities by Ratiometric Profiling of Binding to Glycosylated Surfaces; A Chemical ‘Tongue’ Approach' Accepted. Link

Jones, M. W., Otten, L, Richards, S-J, Lowery, R., Phillips D. J., Haddleton D. M., and Gibson MI. Chem. Sci., 2014, 5, 1611 - 1616 "Glycopolymers with secondary binding motifs mimic glycan branching and display bacterial lectin selectivity in addition to affinity"

Otten, L., Richards,S-J., Fullam, E., Besra, G.S., Gibson, M,I. , J.Mater. Chem. B, 2013, 1, 2665 - 2672, "Gold Nanoparticle-Linked Analysis of Carbohydrate-Protein Interactions, and Polymeric Inhibitors, using Unlabelled Proteins; Easy Measurements Using a ‘Simple’ Digital Camera" Link

Daniel Mitchell has become the most recent PhD to graduate from the lab. He defended his Thesis, examined by Daniell Mitchel (Warwick Medical School) and Vitaly Khutoryanskiy (Reading). Dan's Thesis was on the design of new antifreeze protein mimetic polymers and their translation to cell cryo-storage applications.

Read some of his papers, below;

Mitchell, D. E., et al. (2014). "Quantitative study on the antifreeze protein mimetic ice growth inhibition properties of poly(ampholytes) derived from vinyl-based polymers." Biomaterials Science. 2014, 2 (12), 1787 - 1795Mitchell, D.E, et al. (2015).

"Rational, yet simple design of an antifreeze protein inspired polymer for cellular cryopreservation". Chemical Communications. 2015, DOI: 10.1039/C5CC04647E.

Our contribution the the Book 'Macro-Glycoligands' has been published in Methods in Molecular Biology. Our chapter is a protocol (as with the series in general) describing how to obtained well-defined polymer coated gold nanoparticles with a corona of glycans. This shares our expertise and experience in this area including trouble-shooting to enable others to make these versatile materials. In particular, the use of these to probe lectin-binding is discussed.

Read the chapter here.

Methods in Molecular Biology; Macro-Glycoligands. "Multivalent Glycopolymer-coated Gold Nanoparticles

Caroline Biggs has become the 5th Dr To emerge from the group, having succesfully passed her viva with Dr Andrew Marsh (Warwick) and Prof Paula Mendes (B'Ham) acting as the examiners.

Carolines PhD was entitled ' Biointegrative Polymer Surfaces' and focused on the development of new surface coatings to enable us to probe biological function at complex surfaces, with a particular focus on polymeric tethers for glycans.

Read some of carolines papers below

Richards, SJ, Biggs, CI, Gibson, MI, 2016, Series Vol 1367, Methods in Molecular Biology; Macro-Glycoligands. "Multivalent Glycopolymer-coated Gold Nanoparticles" e-book ISBN 978-1-4939-3130-9; Hard Cover ISBN 978-1-4939-3129-3Congdon, T., Dean, B.T., Kasperczak-Wright, J., Biggs, C.I., Notman, R., Gibson, M.I., Biomacromolecules 2015, 16, 2820 – 2826 , Probing the Biomimetic Ice Nucleation Inhibition Activity of Poly(vinyl alcohol) and Comparison to Synthetic and Biological PolymersBiggs, CI., Edmondson, S,,and Gibson, M.I., Biomater. Sci., 2015, 3, 175 - 181, "Thiol-ene Immobilisation of Carbohydrates onto Glass Slides as a Simple Alternative to Gold-Thiol Monolayers, Amines or Lipid Binding

Our latest work on multivalent glycosylated nanoparticles has been published in Journal of Materials Chemistry B. We are very interested in exploiting glycans (sugars) for biotechnological applications, particularly in infectiou disease. A key challenge is being able to monitor their binding interactions with their partner proteins (or even whole pathogens). Current methods, based on SPR, QCM, NMR etc provide a huge amount of detail but are slow and expensive requiring infrastructure. Here we made use of gold nanoparticles as the sensory component and exploited their red-blue colour shift upon protein binding to monitor their glycan binding. THis was combined with a versatile synthetic approach enabling the facile incorporation of a range of sugars onto the surface of the particles, via a polymeric tether. In addition to probing the binding interactions, we translated this into a point-of-care type biosensor baed upon multiplexing (barcoding) of the sugars to lectins and toxins. We will take this work forward in our quest to make glycan-based diagnostics.

Read the paper here;

Glycosylated Gold Nanoparticle Libraries for Label-Free Multiplexed Lectin Biosensing

Our latest work in the field of studying mimics of antifreeze proteins has been published in Nature Scientific Reports. in this paper we describe our attempts to establish a high-throughput assay to screen for Ice Recrystalisation Inhibition activity; a crucial feature in the search for new cryoprotective agents to store donor cells and organs. Here we build on previous observations that gold nanoparticle aggregation was inhibited by antifreeze proteins, but was correlated with thermal hysteresis. Here we propose a closer match to IRI activity. The assay can be conducted in 96 well plates making it far simpler than our 'splat test' which is slow and not suitable for screening. Using this assay, we observed that serum proteins have weak IRI, which is reduced upon denaturing. This lead us to study other non-antifreeze proteins for IRI, as shown in our recent Biomacromolecules paper

Read the paper here

"Gold Nanoparticle Aggregation as a Probe of Antifreeze (Glyco) Protein-Inspired Ice Recrystallization Inhibition and Identification of New IRI Active Macromolecules"