Category: Success Stories

3 business interaction vouchers awarded

Congratuations to the awardees of three business interaction vouchers awarded in the most recent call:

Assessing the production of human cysteine knot hormones in plant cell cultures
Jose Gutierrez-Marcos, University of Warwick, working with Mologic

This project aims to implement a new methodology designed to streamline the rapid and cost effective production of human chorionic gonadotropin in plants for its use in oncology diagnostics. To this aim we will assess the impact of culture media in protein production, purification and quality, which at present are the major limiting factors of protein production in plant cell cultures.

A machine learning poly-omics classifier to improve protein production in CHO cells
Claudio Angione, Teesside University, in collaboration with the Centre for Process Innovation

Our objective is to combine novel machine learning techniques with poly-omic analysis, building a computational method that: (i) accurately identifies whether target cells have optimal conditions for producing the target protein; (ii) if not, predicts genetic modifications that will likely increase protein production.

Fermentation optimisation of biotherapeutic production by E. coli ‘TatExpress’ strains
Colin Robinson, University of Kent, partnering with UCB-Celltech
We have developed E. coli strains that export a range of biotherapeutics to the periplasm
via the Tat protein export pathway. This project will test and optimise growth under
fermentation conditions to determine their true abilities and capacities using high-throughput ‘ambr’ micro-bioreactor systems to systematically optimise fed-batch fermentation regimes.

Our next (and final) business interaction voucher call closes at midday on Friday 26th May.
Details of other BIVs that have been awarded can be found here.

New proof of concept grants awarded

Congratuations to the awardees of BioProNET proof of concept funding in the 2016 call.

Can archaeal minichromosome maintenance helicases enhance the performance of a
nanopore DNA sequencer?
Michael Plevin, University of York, working with Oxford Nanopore Technologies
This project involves the engineering and production of novel protein nanopores. The collaborators will perform single molecule analyses of enzymes or proteins that transport chemicals or propagate signals across membranes to establish whether nanopore-based single molecule assays can be performed in parallel to generate more data more efficiently. This will provide an opportunity for new areas of research and development in protein biotechnology.

Developing a tool kit for determining the manufacturability of new therapeutics in CHO cells
Andrew Peden, University of Sheffield, working with UCB Pharma
Their project aims to identify bottlenecks in the production process of biologics by directly translating the understanding of basic biological processes into assays which will be useful for assessing the manufacturability of new drugs in mammalian cells. These novel and advanced assays will allow problems in the manufacturing process to be rapidly diagnosed and provide molecular clues to how the problems can be overcome.

BioProNET meetings ignite collaborative project on biologic production

Professor Ian Stansfield from the University of Aberdeen has recently been awarded funding
for a collaborative project investigating how to optimize the production of biologics, which was catalyzed by his participation at BioProNET events.

The production of vaccines, antibodies and other proteins in cell lines can induce cellular stress, which can lead to errors in translation — including ribosome frameshift errors. Such mistranslation can compromise the yield and quality of the protein product, and hence the safety and efficacy of biologics. Ian’s project will pursue a better understanding of causes of translational error through the design and application of novel reporters of mistranslation.

“Initial discussions on this project were started as a result of the BioProNET sandpit meeting, held in June 2015, when I made initial contact with a scientist from the biotechnology company Fujifilm Diosynth Biotechnologies,” says Ian.

As a result of this networking meeting, Ian co-organized a BioProNet-sponsored workshop on recombinant protein authenticity, together with colleagues Mick Tuite and Tobias von der Haar from the University of Kent. Ian commented “The attendance of scientists from Fujifilm at our BioProNET-sponsored workshop in London consolidated ideas for the project”.

The project includes collaboration partner Professor Phil Farabaugh, a molecular biologist from University of Maryland, USA, and physicist Dr Mamen Romano (University of Aberdeen) who will be mathematically modelling gene expression processes. Ian’s group will then use synthetic biology approaches to  couple the output from the new mistranslation sensors to recombinant protein expression, in order to autoregulate mistranslation and the quality of the recombinant protein product.

Fujifilm will test these synthetic gene circuits in in yeast and E.coli to maximise the impact of this research on industrial biotechnology.

More about the project, which is jointly funded by the BBSRC (to Ian Stansfield and Mamen Romano) and the US National Science Foundation (to Phil Farabaugh) can be found here.

New Protein Solubility Predictor Funded by PoC Award

Proof of Concept funding from BioProNET has enabled Jim Warwicker and colleagues from the University to build a webtool that predicts protein solubility. Recombinant biologics often have low solubility, due to their high concentrations, sequence and three-dimensional structure. The accumulation of insoluble protein agglomerates can lead to the formation of aggregates, which can impact biological activity and immunogenicity of a biologic.

Therefore determining the solubility of a protein and its propensity of a protein to aggregate would be of great use to the biopharmaceutical industry and researchers.

The funding from BioProNET enabled Jim and colleagues to develop existing code into a user-friendly web format. Users (anyone!) can paste a single sequence of amino acids into the tool; the software compares this sequence to a benchmark dataset of proteins with known solubility, and then returns a set of calculations that predict solubility of the protein based on its sequence.

The programme calculates a variety of properties — such as amino acid composition, net predicted charge, predicted pI value, ratio of conservative amino acids, propensity for disorder, propensity for forming beta strands and sheets — that indicate how soluble the entered amino acid sequence is likely to be.

The webtool is available here:
http://www.protein-sol.manchester.ac.uk/

The project is already bearing fruit, as it has been used as part of a successful proposal to the EPSRC formulation call. The software is still under development and further improvements, including those based on user-feedback will be added.

Further reading (any new publications from the project will be added)
Chan P, Curtis R, Warwicker J (2013) Sci Rep 3:3333
Warwicker J, Charonis S, Curtis R (2014) Mol Pharm 11:294

Two new business interaction vouchers awarded

Congratulations to Perdita Barran and James Winterburn who have recently been awarded business interaction voucher funding from BioProNET

Perdita, from the University of Manchester will be working with Bio-shape on a project entitled ‘Examining the relationship between charge and zeta potential in proteins using mass spectrometry: implications for formulation and for the use of mass spectroscopy as a screening tool.

James, also from the University of Manchester is partnering with Croda Europe on a project called ‘Novel bioprocessing approaches for the separation of product phases‘ that will investigate if continuous separation of glycolipid biosurfactants from fermentation broth can be achieved at the small pilot scale.