JULY 2016: OVERCOMING CELLULAR BARRIERS: IMPLICATIONS FOR INDUSTRIAL BIOTECHNOLOGY

Overcoming Cellular Barriers: Implications for Industrial Biotechnology – July 6th & 7th 2016

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”This event was great for learning what academic groups are doing and who has the capability and interest in developing collaborative programmes.”

”As a first year PhD student working on membranes this event was a great opportunity to find out about the diverse research ongoing and this exposure will be helpful in addressing problems I will encounter during my next 4 years of my PhD” 


It is increasing recognized that the function of membranes in bacterial, yeast and mammalian cell factories are an important but underappreciated parameter in optimizing recombinant protein quality and yields.  Furthermore, delivery of a therapeutic protein to its target often requires that protein to cross one or more membranes. Therefore, the aim of this meeting was to to bring together academic scientists with diverse interests in; protein trafficking in eukaryotic cells, protein export from bacterial cell factories and delivery of therapeutic proteins to targets, alongside industrial scientists who are interested in improving the challenges of overcoming cellular barriers.

Over 75 BioCatNet, BioProNet and CBMNet members attended the ‘Overcoming Cellular Barriers: Implications for Industrial Biotechnology’ in Birmingham.

The event kicked off with a presentation from CBMNet Director Professor Jeff Green, who defined the objectives of the event.

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Attendees were asked to complete a ‘me profile’ describing who they were, their expertise, their dream project and what the next big development in their field of research would be. You can view the ‘me profiles’ here.

This was followed by a presentation of the available funding options from the BBSRC but Jamie Parkin:

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Next there were a series of talks from academics and industry in 3 sessions.

Session 1: Protein Trafficking in Eukaryotic Cells

Therapeutic protein production by eukaryotic cell factories remains an expanding field, but there are potential barriers as the overproduced proteins navigate the various intracellular components leading either to successful secretion or protein recycling.  A better understanding of how cell factories support overproduction of proteins will provide opportunities for intervention and improved product quality and yields.

To address this Dr Bernie Sweeney from UCB, spoke about how UCB are beginning to address protein trafficking both  in-house and with external collaborators. This was followed by Dr Andrew Peden, The University of Sheffield, who spoke about obtaining a molecular understanding of antibody secretion. You can see Andrew’s presentation here.

Session 2: Protein Export from Bacterial Cell Factories: Chair Professor Jeff Green

The workhorse of biotechnology, E. coli, is a poor chassis for exporting recombinant proteins, but is being improved by exploiting Tat and autotransporter systems.  Better understanding of the native bacterial secretory machinery and application of synthetic biology approaches to exploit the relaxed substrate specificities of native protein translocases and introducing heterologous systems offers opportunities to improve production and recovery of target proteins.

To address this Dr Neil Dixon and Dr Steve Williams from The University of Manchester and Cobra Biologics discussed their collaborative project ‘PeriTune’, which is researching periplasmic export in e. coli. This was then followed by Dr Kelly Walker, The University of Kent, who spoke of their research in to the Tat pathway as a biotechnological tool for the expression and export of heterologous proteins in Escherichia coli. You can see Kelly’s presentation here.

Session 3: Delivering Therapeutic Proteins and other compounds

Many proteins and peptides possess biological activity that makes them potent therapeutics, with targets inside the cell.  Still, the use of proteins and peptides as therapeutic agents is hampered by the whole set of their intrinsic properties associated with their nature as complex macromolecules, which are, as a rule, foreign to the recipient organism. Low permeability of cell membranes to macromolecules often represents an additional obstacle for the development of peptide-based and protein-based drug formulations. To overcome this it may be possible to exploit the fundamental knowledge of the structure/function of transporters and their ability to recognize modified substrates as clients, for example in developing peptide-modified drugs that are more effectively taken up through the gut via peptide transporters.

To address this Ron Jackson from MedImmune disucssed engineering therapeutic proteins for cell entry: the natural approach. You can see Ron’s presentation here. This was followed by a talk from Dr Rongjun Chen, Imperial College London, on Engineering biomimetic polymers for intracellular protein delivery.

Following on from the three sessions Professor Jeff Green gave a review of presentations and provided some ‘scene-setting’ for discussions to follow. Attendees then spent the rest of the day formulating potential project ideas and developing these new collaborations.

This was then followed by a group dinner where further networking took place, along side watching the football!

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The second day started with interesting talks about ‘technology drivers’ from Professor David Stephens, The University of Bristol, who talked about high resolution imaging of secretory cargo export from the endoplasmic reticulum. Dr Boyan Bonev, University of Nottingham, then spoke about molecular interactions in membranes and applications of solid state NMR.

Attendees then split up again in to groups to further develop project ideas. At the end of day two 9 project ideas were generated and champions assigned to take these projects forward.

As a result of this event 5 CBMNet BIVs were awarded:

Business Interaction Voucher Investigation into the effect of increased cytoplasmic membrane invaginations on secretion during industrial fermentation systems. University of Kent FujiFilm Diosynth Biotechnologies
Business Interaction Voucher Investigation of effect of recombinant outer membrane vesicle production on secretion in industrial fermentation systems. University of Kent FujiFilm Diosynth Biotechnologies
Business Interaction Voucher Testing a prototype engineered bacterial flagella Type III Secretion System for ‘true’
protein secretion in biotechnology – a Proof of Concept study
University of Sheffield FujiFilm Diosynth Biotechnologies
Business Interaction Voucher Efflux from bacteria of feedstocks for industrial manufacture University of Leeds Lucite
Business Interaction Voucher Optimization of influenza vaccine manufacturing through modification of cellular membrane organization. University of Kent MatTek Corporation

”I thought the selection of talks was excellent. I came across people working in areas I would not normally meet and it was most stimulating.”  

”I really enjoyed the event and learnt a lot about different techniques and systems.”