13 ERA IB: ProSeCa - Recovery of high value Proteins from Serum by innovative direct Capture techniques

Lead Research Organisation: University of Birmingham
Department Name: Chemical Engineering

Abstract

Many pharmaceutical drugs are made by extracting them from natural sources. However, many of these extraction methods are old-fashioned and inefficient. An example that we will be working on in this project is the extraction of veterinary drugs from equine (horse) serum. Current methods are complicated and cannot generate large yields of these veterinary drugs in a cost- and time-efficient manner. In addition, some current methods can damage the drug products, further lowering yields.

We aim to use magnetic technology to separate products from horse serum for use in veterinary medicine. We will develop methods to efficiently purify these products using a variety of approaches, all centred around the use of powerful magnets. The overall objective of the project is to develop these methods to a point where they can be applied commercially; this will be achieved by the design and development of procedures and equipment that can be implemented in a commercial setting. The overall objective is to decrease the overall time and cost of production of veterinary drugs; methods and techniques developed in the project may also be applied for the manufacture of human medicines, leading to benefits to the general public and medical profession.

Technical Summary

The extraction of biopharmaceuticals from natural sources often employs overly complicated antiquated procedures. The downstream processing of serum is a case in point; it comprises large numbers of steps of low purification power and consequently delivers poor overall product yields.

Parallel advances in magnetic separation equipment and approaches to manufacture magnetic affinity particles, funded through several national and EU funded projects lay the foundations for the proposed work. Using magnetic bioseparation techniques, the consortium will seek to replace outdated organic solvent based fractionation methods, which can inflict serious damage on especially prone protein targets.

In ProSeCa, our combined expertise will be applied to the production of protein based veterinary medicines from horse sera, centring on harmonious integrated use of: highly selective magnetic adsorbents manufactured via: (i) chemical; (ii) biological; and (iii) mixed 'biological/chemical' routes; with a fully automated and cGMP compliant magnetic separator.

Planned Impact

This project will specifically benefit researchers working within academia and businesses in the UK, the EU and worldwide. It will also generate impact for the general public through enhanced health and wellbeing, and the public sector through decreased drug costs.

The project will develop new methods to purify and process protein biopharmaceuticals. The objectives are process simplification and increases in process efficiency, leading to more rapid process development and more rapid protein purification. The focus in this project is equine medicine, but materials, equipment and methods developed in this project could also be applied (following the project) to other veterinary pharmaceuticals and human pharmaceuticals. This would benefit academics working in pharmaceutical development (drug design and discovery and manufacture) as well as the pharmaceutical and veterinary pharmaceutical industries. More effective processing tools for biopharmaceuticals could also enable biopharmaceutical drugs to get to market more rapidly and lower process costs, leading to improved economic competitiveness. Currently, the vast majority of protein biopharmaceutical production costs are derived from purification. The UK bioprocessing sector would potentially greatly benefit from outcomes of this project. The timescale for the translation of these project outcomes to industrial uptake is likely to be within 5-10 years of the project ending; integration of novel technologies into human biopharmaceutical production would take longer due to considerable regulatory pressure, although the technology could be more rapidly translated into other areas such as nutraceutical manufacture or veterinary medicine.

Faster time to market (thereby more rapid drug development pathways) and lower drug costs would benefit the general public, increasing health and wellbeing, by ensuring that new therapies would more rapidly be available and would be available to more people. Decreased drug costs would enable greater value for the NHS and thus UK government.

More fundamental technology that will be developed during the project (assay development; synthetic biology) will also generate impact. Synthetic biology of non-model organisms is an underrepresented area within synthetic biology, so this project will benefit academic and industrial researchers working in that area. This could potentially impact on biofuel and platform chemical production and bioremediation, to name three areas. Biofuels and biological platform chemical production both reduce reliance on fossil fuels and enable greater sustainability, with resultant environmental (lower emissions and waste) and economic benefits (rising costs of crude oil and energy, rising costs associated with waste discharge and carbon emission). Bioremediation also allows greater sustainability, land reuse and potential health benefits. These would have clear impacts for UK and EU business, government and the general public.
 
Description We have optimised growth methods for bacteria that contain magnetic particles. These bacteria are hard to grow, so developing methods for their intensified growth is important so that they might be used industrially. We have succeeded in developing methods for the growth of these organisms, and novel methods of analysis to monitor growth of these organisms.

We have developed methods for the release and purification of magnetic particles from these organisms. We have optimized these methods so that we can now generate larger quantities of purer particles than before.

We have genetically modified this organism in order to change the functionality of the magnetic particles generated by the organism. The overall outcome is that we have optimized multiple stages of the process of production of these particles, so that industrial-scale production is possible.
Exploitation Route Findings from the project have been presented at conferences (one abstract has been published) and as two peer-reviewed publications. Two further peer-reviewed manuscripts are in progress: one has been submitted, covering optimization of the fermentation process; and one is in preparation, detailing whole-process optimization. As such, project outcomes will be able to be used by other scientists and engineers for the development of new processes for the bioproduction of magnetic particles. In addition, we envision future grant applications being submitted to further the work in the area.
Sectors Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology

 
Description General travel grant to Postdoctoral researcher to attend ECB2016 conference
Amount £400 (GBP)
Organisation Biochemical Society 
Sector Charity/Non Profit
Country United Kingdom
Start 07/2016 
End 07/2016
 
Description Travel grant to Postdoctoral researcher to attend ECB2016 conference
Amount £350 (GBP)
Organisation Microbiology Society 
Sector Learned Society
Country United Kingdom
Start 07/2016 
End 07/2016
 
Title Growth of magnetotactic bacteria 
Description Magnetotactic bacteria are fastidious in terms of growth conditions. We have developed methods to grow these organisms in the laboratory, both in small scale cultures and in bioreactors. Growth in bioreactors has been optimised to permit high cell density culture. 
Type Of Material Biological samples 
Provided To Others? No  
Impact The ability to grow these organisms is essential for this project to proceed. The methods will be expanded upon in this project and in linked projects that will be spun out of this project. 
 
Title Isolation of magnetic particles from magnetotactic bacteria 
Description Methods have been developed to allow magnetosomes, biologically-generated magnetic particles, to be isolated from magnetotactic bacteria and to be purified. 
Type Of Material Biological samples 
Provided To Others? No  
Impact These methods are essential for the success of this project. It is anticipated that these methods, when optimised, will be published in a peer-reviewed journal. These methods will also be shared with project partners. 
 
Title Purification of magentosomes 
Description Methods were developed to effectively purify magnetosomes. 
Type Of Material Biological samples 
Year Produced 2017 
Provided To Others? No  
Impact Future work on the use of magnetosomes will use the techniques developed within this project. The methods have been incorporated into a manuscript for submission to a peer-reviewed journal. 
 
Description Research visit to CEA-CNRS Cadarache (France) 
Organisation Alternative Energies and Atomic Energy Commission (CEA)
Country France 
Sector Public 
PI Contribution Travel expenses, staff time and consumables for experimental work
Collaborator Contribution Accommodation, travel expenses, staff time, access to research equipment and consumables for experimental work
Impact - Exchange of ideas for future research. Joint application for a fund to support a seed meeting for Franco-British collaboration to European networks. Experimental study related to the magnetic properties of magnetotactic bacteria.
Start Year 2016
 
Description Seminar at the NIHR SRMRC Research Forum Meeting 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact 50 academics/medical practitioners form the University of Birmingham attended the seminar <> This was followed by questions and discussions and the attendants reported interest in the subject.
Year(s) Of Engagement Activity 2016
 
Description University of Birmingham Community Day 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact The activity was split into two sections:

1. Synthetic Biology is about engineering biology. This activity is focused to an audience 8-14 years old, and their parents. It will involve the use of Lego Bricks and using elements that mimic synthetic biology components (i.e. promoter, RBS, repressor and terminators,...). The kids will be acting as the chassis organism to obtain the necessary tools to build an animal creature that they can take home with them. We will also observe microbes in a microscope and browse the comic strip "Adventures in Synthetic Biology".

2. The adult audience attending the community day were asked questions about their acceptance of genetically modified food and the use of GM technology in medicine manufacture. These questions engaged the adult audience and generated interesting discussions as the public have different perceptions when consuming products of different types that are produced in GMOs.
Year(s) Of Engagement Activity 2015