Tag Archives: Lincoln

13 New CBMNet Projects Funded

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13 New CBMNet Projects Funded

We are pleased to announce that we have recently funded 13 new projects in Industrial Biotechnology and Bioenergy. 

Proof-of-Concept Projects

  • Dr Neil Dixon, University of Manchester, CPI and Oxford Biotrans – Identification of Membrane Transporters of Lignin monomers
  • Professor David James, University of Sheffield and UCB Pharma – Engineering Exosome Production by CHO Cells
  • Professor Doug Kell, University of Manchester and Croda – A potent synthetic biology strategy for increasing transporter-mediated terpenoid efflux from E. coli

Business Interaction Vouchers

  • Dr Mark Shepherd, University of Kent and FujiFilm – Engineering E. coli for enhanced production of antibody fragments
  • Dr Mark Shepherd, University of Kent and FujiFilm – Lowering the disulphide load in the periplasm of E. coli cell factories
  • Dr Teuta Pilizota, University of Edinburgh and FujiFilm – Replacing osmotic downshocks with upshocks for periplasmic protein extraction

Vacation scholarships

  • Dr Frans Maathuis, University of York – The role of HMA and COPT proteins in trans membrane movement of palladium 
  • Professor Colin Robinson, University of Kent – An enhanced platform for translocation of biotherapeutics to the E. coli periplasm
  • Dr Alan Goddard, University of Lincoln – Modelling of multifactorial solvent stress on membranes
  • Dr Wuge Briscoe, University of Bristol – Bacterial mimicking liposomes
  • Dr Boyan Bonev, University of Nottingham – Membrane stability models in the presence of methacrylate esters
  • Dr Sam Miller, University of Aberdeen – Investigating the role of periplasmic and transmembrane domains of mechanosensitive channels in E.coli membrane integrity
  • Dr Claudio Avignone-Rossa, University of Surrey – Construction of glucose transporter mutants of Clostridium beijerinckii

You can view all our projects funded to date here and read our success stories here.

CBMNet research targets efficient renewable chemical production

New research led by a biochemist from the University of Lincoln, UK, will aim to improve the production of an important renewable chemical used in many well-known products.

A major new collaboration has been awarded funding to explore ways of improving the production of n-butanol – a central building block for a number of household and industrial substances. It occurs naturally as a product of the fermentation of sugars and other carbohydrates and is used in a range of domestic and industrial products, predominantly in paints and coatings, but also in diverse areas such as perfumes, food ingredients, natural resins, and as an extractant in the manufacture of antibiotics and vitamins.

Dr Alan Goddard, from the University of Lincoln’s School of Life Sciences, will lead the project with Dr Preben Krabben from Green Biologics Ltd and Professor Ian Graham and Dr Tony Larson from the Centre for Novel Agricultural Products at the University of York.

The collaboration has been awarded a CBMNet (Crossing Biological Membranes Network) grant to explore more efficient and cost-effective ways of generating n-butanol from a variety of feedstocks – the term used to describe plant and algal materials in the production of renewable chemicals. In particular the purification step of n-butanol from the natural fermentation process can be expensive and the research aims to contribute towards improving this process.

Using expertise developed at the University of York, the researchers aim to identify the specific changes that occur during the creation of n-butanol. The changes that are identified will then be incorporated into a new model system, developed at the University of Lincoln, with a view to improving the production process and enhancing the yield.

Dr Goddard, Senior Lecturer in Lincoln’s School of Life Sciences, said: “The funding awarded by CBMNet will provide an exciting opportunity for our lab to continue industrially-relevant collaborations with Green Biologics Limited. The award will benefit the work of Green Biologics Limited as well as provide new opportunities for researchers here at Lincoln. I hope that our partnership will continue to develop based on the findings of this work.”

The project, called ‘Identifying and characterising protective lipid changes under solventogenic stress’, is funded through a CBMNet Proof of Concept Grant of just over £30,000. The CBMNet Proof of Concept Grants support new multi-disciplinary teams as they develop innovative solutions to overcome bottlenecks in the Industrial Biotechnology and Bioenergy (IBBE) sector.

Read the original article here.

CBMNet Business Interaction Vouchers Awarded

We are pleased to announce that we have awarded two new Business Interaction Vouchers.

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Dr Pandhal, The University of Sheffield and Celbius – Acoustical modifications to increase recombinant glycoprotein expression from engineered E. coli cells

​The demand for protein therapeutics is increasing with the human population, which is predicted to top 9 billion by mid-century. In addition, the biopharmaceutical industry landscape is changing as a result of shifting customer demographic (e.g. higher population increases in less developed countries), the rise in potential for personalised medicine (i.e. a move to manufacture smaller volumes and more diverse libraries of drugs) and the increasing availability of drug biosimilars as patents for big blockbuster drugs come to an end. A majority of the complex drugs are currently produced in mammalian cell lines, where rapid advances in cultivation techniques have improved productivity. However, these cell lines are expensive to grow and more difficult to manipulate genetically. This means that expanding the toolbox of simpler, easier-to-control and manipulate production cell lines, for example E. coli, is particularly desirable and timely. E. coli is currently used to make simple drugs like insulin but work is underway to enhance the capability of these cells to modify proteins with the addition of specific sugars (complex drugs) or provide a site specific attachment molecule for in vitro modifications. Unfortunately the process is very inefficient and requires massive improvement in cell line ability as well as process technologies. This project proposal aims to combine the expertise of the industrial partner in ultrasonication methodologies and the PI’s skills in glycoprotein production in bacteria, with the application of ultrasonic frequencies to improve not only growth of E. coli cells but also the transfer of lipid-linked sugars and proteins across internal membranes. Ultimately this could improve the productivity of E. coli cells where a larger proportion of total recombinant proteins have the required sugar modification. A range of ultrasonic frequencies will be tested using a specific E. coli cultivation rig incorporating ultrasonic waves.

Dr Alan Goddard, The University of Lincoln and Green Biologics Ltd – In vitro and in silico models of n-butanol-membrane interactions

For nearly 100 years, Clostridia bacteria have been used to make valuable chemicals including acetone, butanol and ethanol.  Purification of these products can be both difficult and expensive, but can be made easier and cheaper by increasing their concentrations in the fermentation broth.  The problem with this is that the products can be toxic to the bacteria which produce them; any mechanism which provides protection to the bacteria is highly desirable.  It is also largely unknown how the bacteria export the solvents from where they are made inside the cell.

Bacteria are surrounded by a membrane made of phospholipids and one mechanism bacteria use to protect themselves from toxicity is to change the lipid composition of this membrane.  This may well provide a viable approach to protecting cells but is very difficult to do in cells.  Ideally, it would be beneficial to know exactly which changes are protective before modifying the bacteria.  To do this, we will test isolated membranes which separate two liquid chambers to model n-butanol movement across membranes.   In concert with this, we will use computer simulations of membranes to model both the direct interaction of n-butanol with membranes and its movement across them.  This will allow us to establish a system in which we can investigate the protective effect of changing the membrane content.  In the long term, these changes can be applied to living bacteria to improve the production of these valuable biofuels.

 

New CBMNet funded projects awarded

We are pleased to announce that we have awarded two new Proof of Concept awards and one Business Interaction Voucher.

The University of Nottingham will be working with Croda Europe on the project ‘Solid state NMR analysis of lipid/surfactant interactions’, funded through a CBMNet Business Interaction Voucher.

Surfactants, including soaps, are compounds, the molecules of which possess a dual affinity for water, both attracting and repelling it. They disrupt lipidic structures, such as the membranes of bacteria and higher organisms alike. In this proposal, we aim to investigate the effect of bioproduced industrial surfactants on lipid bilayers, membrane models, to understand the mechanisms of surfactant function, to understand and optimise stability of
bioproduction and to gain insights into cellular stability in the presence of these surfactants. To achieve this, we will use advanced analytical methods, including solid state nuclear magnetic resonance (NMR), to investigate the stability of lipid bilayers in the presence of varied amounts of surfactant. Spectra, obtained from naturally present phosphorus atoms in the membranes, provide a sensitive tool for quantitative assaying of lamellar to non-lamellar conversion in the presence of surfactants.

The University of York, along with TeeGene Biotech Ltd and Johnson Matthey will be working on the project ‘Plants as Nanoparticle Producers’, funded through a CBMNet Proof of Concept Grant.

Platinum group metals (PGMs) are used in many industrial applications, often as nanoparticles (NPs). PGMs are rare materials, making them highly valuable, but their increasing dispersal in the environment is of growing concern. The metal accumulating ability of plants can be used to capture metals from the environment. Furthermore, our studies demonstrated that plants can produce PGM-NPs which can make high-performing plant-based catalysts, either in their native state or after modification. These high value products could help satisfy demand for precious metals in industry and medicine. However, the full potential of plants as PGM accumulators is yet to be realised and will critically depend on the mechanism for PGM uptake, an area of great controversy. The aim of this study is to establish whether PGM uptake in plants is via passive diffusion or mediated by (specific) proteins.

The University of Lincoln, along with Green Biologics Ltd will be working on the project ‘Identifying and characterising protective lipid changes under solventogenic stress’, funded through a CBMNet Proof of Concept Grant.

Solventogenic Clostridia are used by Green Biologics Ltd (GBL) to generate n-butanol from a variety of feedstocks providing sugars for fermentation.  n-Butanol is expensive to purify from the fermentation broth but the cost of in situ solvent removal is greatly decreased by fermenting to higher concentrations of n-butanol.   One particular challenge is that n-butanol is toxic to Clostridia at concentrations in excess of ~2% and metabolism slows down at substantially lower butanol concentrations.  A previous BIV between Alan Goddard (AG) and GBL determined that n-butanol directly disrupts model lipid bilayers made from extracted Clostridia membranes.

It has been reported that a number of changes in lipid composition of the plasma membrane occur in response to n-butanol production.  One specific class of lipids, plasmalogens, are potentially important in this process and have been shown to be upregulated in Clostridia under solventogenic stress.  Plasmalogens are ether phospholipids characterized by a vinyl ether linkage at the sn-1 position and an ester linkage at the sn-2 position and may influence the structure and function of the membrane when exposed to stresses such as n-butanol.  Using lipidomics expertise developed by Professor Ian Graham (IG) and Dr Tony Larson (TL) at the University of York, this proposal aims to determine the specific changes in plasma membrane lipid composition during n-butanol formation and to investigate their effects on membrane stability in the presence of n-butanol with a view to being able to modulate this system for enhanced biofuel production.