We have a vacancy for an ambitious PDRA to work on our new cell cryopreservation technology. This role is to undertaken world-class cell biology to understand how our macromolecular (polymer) antifreeze protein mimics enable cells to survive cryopreservation, with the long term aim of reducing, or removing, the need for organic sovlents in cryopreservation. A particular aim of this project is to enable the cryopreservatino of donor stem cells, so the candidate will have experience of using primary human tissue, and all necessary analytics (microscopy, flow cytometry). We work as a team, spread over 4 laboratories in the Medical School and the Department of Chemistry, so a strong team-ethic is essential.

Apply here!

Our latest work on trying to understand, and mimic, how antifreeze glycoproteins (AFGPs) function to slow ice growth has been published in the Journal of the American Chemical Society. AFGPs have several macroscopic properties due to their ability to influence ice crystal growth but it is not fully clear how they work, or how they recognise ice faces. There is no crystal structure of antifreeze proteins, so the 3-D structural information is still missing. In this work, we build upon our previous observations that amphipathic helicies (compounds with hydrophilic and hydrophobic faces) are potent ice growth inhibitors, and that solution-state studies of AFGPs suggest they have a defined hydrophobic face which binds to ice. We show that by synthesising polymers with a sugar on one face, and a hydrophobic opposing face we can selectively introduce the ability to slow ice growth. This is improtant as it shows that the sugar alone is not the essential component but rather the spacial segregation of different units along a polymer backbone.

Read the paper here

Facially Amphipathic Glycopolymers Inhibit Ice Recrystallization

Professor Gibson has been awarded an ERC Proof of Concept Grant entitled 'Solvent Free Cryopreservation of Hematopeotic Stem Cells'. This grant is only available to ERC grant holders, to follow up on results obtained during the ERC grant to translate it to real world applications. This project will seek to revolutionise how we store bone marrow cells (hematopoetic stem cells) by using polymeric mimics of antifreeze proteins.

A Postdoctoral vacancy will be available soon on this project.

We have a vacancy for an administrative coordinator to join us. The role will be to help with the administration of the large and diverse group, split between the Chemistry Department and The Medical School and to provide clerical support to Professor Gibson.

Job advert, and application details are here;

Dr Antonio Leazza has joined the group as a research fellow. He is supported by a Newton Fund/CNR (Italian) Fellowship for outstanding early career researchers. He did his PhD in Naples working on the synthesis of complex sulphated glycans and will bring new carbohydrate chemistry skills to the group.

Check out his personal page (in progress) here.

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

Multivalent Antimicrobial Polymer Nanoparticles Target Mycobacteria and Gram-Negative Bacteria by Distinct Mechanisms

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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

Synthesis of Degradable Poly(vinyl alcohol) by Radical Ring-Opening Copolymerization and Ice Recrystallization Inhibition Activity

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

Polymer mimics of biomacromolecular antifreezes