Gibson Group News
Antimicrobial Nanoparticles in Biomacromolecules
Antimicrobial resistance to current drugs is an urgent global healthcare threat. New treatments are diagnostics are urgently needed, otherwise a simple cut may lead to serious infections in the future. Traditional small molecules drugs work by targetting a specific enzyme (typically) and requires permeation into the bacteria to function. Antimicrobial peptides are well known as Natures own defense against bacterial infections; these are typically rigid positively charged peptides and there are many reports of using polycations to mimic these. However, these are typically tested against Gram negative bacteria only. In our latest paper we investigate polymer-coated coated nanoparticles for their activity against E.coli and mycobacterium smegmatis, which is a Mycobacteria containing a complex cell wall rich in glycans. We show that multivalent presentation of the polymers on nanoparticles increases the activity (on a per polymer and mass basis) but crucially this increase in actiivty is due to different mechanisms against each strain. Against E.Coli membrane lysis is seen and the particles are bacteriocidal (kills them!). However, against mycobacteria the particles are bacteriostatic (stops them growing) and there is not signficant membrane lysis. This shows that the current assumptions that all polycations function by simple membrane lysis is not correct and that deeper investigations to understand their function is essential.
This work was conducted in collaboration with Dr Elizabeth Fullam's lab at Warwick, who are experts in pathogenic bacteria including Mycobacterium Tuberculosis and follows on from our previous collaborations into new drugs and polymer antibiotics
Read the paper here
.
Degradable PVA's Published In ACSMacroLetters
Our latest work has been published in ACS MacroLetters, in collaboration with the Dove Group. In this work we reported the synthesis of degradable poly(vinyl alcohol) and its application as an inhibitor of ice growth. Like most vinyl-derived polymers PVA is not biodegradable (except by some environmental organisms) due to its all carbon backbone. Here we make use of the monomer MDO (2-methylene-1,3-dioxepane) which undergoes radical (co)polymerization but results in main-chain ester linkages, rather than C-C bonds, and hence makes the resulting polymers biodegradable. To enable copolymerization, chloro vinyl acetate was used, rather than vinyl acetate, enabling us to selectively remove the protecting groups rather than the backbone esters.
Using this strategy we made a panel of PVAs and showed that the esters were incoporated into the backbone. We then used these to inhibit ice growth, which we have found to be a useful tool to improve the cryopreservation of cells. A key finding was the amount of MDO (and hence esters) which was incorprorated was a crucial factor with too much MDO leading to know ice growth inhibition activity.
Read the paper here
Paper Identifying 'lost' microplastics in Ocean Samples Published
The first paper from our collaboration with Joseph Christie-Oleza in the School of Life Sciences has been published in ACS Envirnomental Science and Technology. There is a huge, and growing problem of plastic (intractable polymer) waste in the environment, especially in oceans. This plastic waste causes huge environmental damage, but there is still a problem identifying the material in ocean water samples. Current methods involve a net, which captures large pieces of plastic, but the smaller microplastic (which could enter the food chain, for example) are often missed. In this work, a protocal for identifying the microplastics using a simple fluorescent dye and image analysis is introduced.
Read the paper here
Antifreeze Protein Mimetics Published in Nature Communications
Our review article highlighting recent progress in the field of macromolecular mimics of antifreeze proteins has been published in Nature Communications. Our last review on this topic was in 2010, (and was the first independant paper from the group!) when the field had not yet emerged and it was not clear what role synthetic polymers would play. Since then, there has been an increase in interest in this field including our own important contributions.
In this review we summarise the background to antifreeze proteins and some models of how they function. We then detail small molecule mimics, but mainly focus on polymeric (or supramolecular) mimics which are emerging as potent ice growth inhibitors as well as new cryoprotectants. The article was a real team effort by 'Team Cryo'.
Read the article here
Our research highlighted in Scientific American
Our recent paper Antifreeze Protein Mimetic Metallohelices with Potent Ice Recrystallization Inhibition Activity has been featured in Scientific American (a monthly US science magazine with a circulation ~ 0.5 million). In this article they highlgihted our collaborative work with Peter Scott and David Fox on designed amphipathic helicies which have the unique ability to slow ice crystal growth. These helicies provided understanding for how native antifreeze proteins, which are often helical, prodcue their antifreeze effects through their structure and not necessarily through a lock-and-type type interaction with the ice surface - although this is still under investigation in our lab.
Read it here
Nature-Inspired Antifreeze Molecules Could Keep Organs Fresh Longer
Matt Gibson gives keynote lecture at German Society of Biomaterials Conference
Professor Matthew Gibson gave a keynote lecture on friday (10th November) at the Annual Conference of the Germany Society for Biomaterials, this year held in Weurzburg. This is a large annual meeting with 300+ attendees. Prof Gibson discuss recent sucesses in developing new biomaterials to help cryopreserve cells, with a focus on how these could advance and simplify how we do cell based assays. He revealed new results from the lab into storing frozen-cells whils still attached to the the tissue culture plastic - this is a major advance to simply cell culture, which currently has a lot of steps and waiting between thawing cells in vials, and conducting the research.
Read our latest paper on this topic here
Paper Published in ACS MacroLetters
Our latest work in collaboration with the O'Reilly Group, undertaken by Lewis (about to start PDRA at CSIRO, Australia) has been published in ACS Macroletters. In this work, we used polymerization-induced self assembly (PISA) to encapsulate proteins within the core of polymer vesicles. PISA has several advantages include that the hydrophobic block is formed in situ from a water soluble monomer; this means that it is easy to encase the protein in the luman (core) compared to traditional methods. However, during the course of this work, we observed that the hydrophobic core (poly(hydroxylpropyl methacrylate), which is actually quite hydrated) did not form a permanent barrier. It was found to actually be permeable. Using this observation we were able to show that enzymes encapsulated within the core could catalyse reactions of externally added reagents, which could cross inside, react, and the subseqently diffuse back out. The importance of this work is it verstility; we used multiple enzymes to prove that this effect is real and also show there is some size selectivity, and these can be considered to be 'molecular sieves'.
Read the paper here
Permeable Protein-Loaded Polymersome Cascade Nanoreactors by Polymerization-Induced Self-Assembly
Matt Gibson delivers invited Seminar at Queen Mary, University of London
On wednesday 25th October, Professor Gibson gave an invited lecture at QMUL, hosted by Dr Julien Guotrot. During this lecture Matt introduce the audience to the challenges of cell storage, and the urgent need for new methods for the distribution of donor cells for regenerative medicine and basic cell biology. He also introduced two recent papers from the group, looking at self-assembled ice growth inhibiting metallo-helicies and also introducing polyproline as a new simple mimic of antifreeze proteins.