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.

 

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