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4 New CBMNet Business Interaction Vouchers Awarded

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4 New CBMNet Business Interaction Vouchers Awarded

We are pleased to announce that as a result of our July meeting ”Overcoming Cellular Barriers for Industrial Biotechnology” we have awarded 4 new business interaction vouchers:

  1. University of Kent and FujiFilm Diosynth Biotechnologies – Investigation into the effect of increased cytoplasmic membrane invaginations on secretion during industrial fermentation systems
  2. University of Sheffield, University of Cambridge and FujiFilm Diosynth Biotechnologies – Testing a prototype engineered bacterial flagella Type III Secretion System for ‘true’ protein secretion in biotechnology – a Proof of Concept study
  3. University of Kent and MatTek Corporation – Optimization of influenza vaccine manufacturing through modification of cellular membrane organization
  4. University of Kent and FujiFilm Diosynth Biotechnologies – Optimization of influenza vaccine manufacturing through modification of cellular membrane organization

Celbius and Sheffield University awarded a CBMNet Business Interaction Voucher

Celbius and Sheffield University awarded a Business Interaction Voucher

Low power ultrasound can affect the performance of many different fermentation processes. Celbius, in collaboration with Dr Jagroop Pandhal at the University of Sheffield, is investigating the effects of sonication on the expression and activity of certain proteins in E. coli. This organism is a work-horse of the biotechnology industry, and responsible for the production of many proteins for pharmaceuticals and biocatalysis. The collaboration was established via Celbius’ membership of the CBMNet (Crossing Biological Membranes), a BBSRC NIBB, and the work will be funded through the award of a Business Interaction Voucher.

http://www.celbius.com/index.php/news

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 secures major new industrial biotechnology funding

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The chemicals industry is a vital component of the world economy that is faced by the need to provide innovative and sustainable solutions to provide the resources required for a growing global population. One approach to a more sustainable chemicals industry is the use of microbial cell factories to produce key chemicals from sustainable feedstocks. However, a major barrier to commercial cell-factory-based chemical production is poor product yield. Often this is caused by intoxication of the cells resulting in sub-optimal performance. To address this problem, a £3 million research project (DeTox) to improve the sustainable production of chemicals and biofuels by microbes has been awarded by the Industrial Biotechnology Catalyst fund to a consortium of scientists led by the Sheffield-based Biotechnology and Biological Sciences Research Council (BBSRC) Crossing Biological Membranes Network in Industrial Biotechnology (CBMNet). Professors Jeffrey Green and David Kelly along with Dr Susan Molyneux-Hodgson at the University of Sheffield are working with colleagues at the Universities of York, Nottingham and Cambridge and five companies (Green Biologics, ReBio, Lucite, CPI and Ingenza), to overcome poor product yields by focussing on how the properties of the bacterial cell membrane can be modified to create more robust cell factories.

DeTox is led by the CBMNet co-director Dr Gavin Thomas (University of York) and has benefited from funding from a CBMNet Business Interaction Voucher (BIV) which generated some of the preliminary data underpinning the DeTox project.

“The BIV was very successful from our point of view as we trialled a new method in our lab, which we took right through to the point where we generated novel data. This then went straight into a grant application.”

Dr Gavin Thomas

“The DeTox project is an exciting opportunity to improve the efficiency of cell-based chemical production that emerged from the creative discussions within the CBMNet management board and our industrial partners.”

Professor Jeffrey Green, CBMNet director

Importantly, the project includes a sociological study of collaborative research processes to develop a better understanding of ‘responsible innovation’.

“The approach of integrating sociological study into a technical scientific project is becoming more common, and it’s an approach that has already been shown to add enormous value to research. We’re very much looking forward to working alongside the scientists and engineers in this important research.”

Dr Molyneux-Hodgson, an expert in the social aspects of synthetic biology in the Department of Sociological Studies

“Green Biologics are looking forward to working with the academic community over the next five years. It is with great pleasure that the wider UK academic community has recognised Clostridia as an important industrial microbe and hopefully this will lead to a dynamic and vibrant community.”

Dr Preben Krabben, Head of Innovation at Green Biologics

DeTox is only one of the many achievements of CBMNet. So far it has funded seven Proof-of-Concept grants along with seven Vacation Scholarships (worth over £175,000) and five Business Interaction Vouchers (worth over £50,000). Many of these awards have focused on supporting students and early career researchers to ensure that the biotechnology expertise continues to grow.

“In our first year we have begun to establish an active and engaged community of industrialists and academics. We now need to build on these foundations and promote the importance of an appreciation of the impact that membrane biology can have on industrial biotechnology processes through our project funding streams and meetings.”

Professor Jeffrey Green

CBMNet is always seeking to further strengthen its links with industry so that the expert knowledge of the UK ‘membrane research’ community is translated into improved biotechnological processes. As the network continues to expand, the sum of its collective knowledge will be a significant resource for the UK biotechnology industry to draw upon.

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.