PeriTune - a clonal optimisation platform

Lead Research Organisation: University of Manchester
Department Name: Life Sciences

Abstract

A variety of micro-organisms including E. coli and S. cerevisiae (baker's yeast), are used in commercial bio-production processes to manufacture a number of products, ranging from high-value low-volume products, such bio-therapeutics (e.g. recombinant insulin), to mid-value products, (e.g. biocatalysts and specialised chemicals), to low-value bulk commodity products (e.g. succinic acid and biofuels). This project will seek to develop a robust clone optimsiation platform for the potential use and application in the above industrial sectors, and so would be of great benefit in a number of applied and fundamental areas of biological and biomedical R&D.

Technical Summary

The aim of this collaboratory Early Stage Feasibility project is to develop a protein expression optimisation platform for the robust production of biologics. This platform will enable key bottlenecks and manufacturability challenges of recombinant proteins used in Industrial Biotechnology to be addressed. The platform will utilize the tuneable gene expression control technology RiboTite, developed at the University of Manchester. This technology operates at the level of translation initiation and permits cellular-level tuneable control of gene expression. Clones developed through the optimisation platform will be validated, demonstrated at scale, and assessed for manufacturability.

Planned Impact

As described in proposal submitted to TSB

Publications

10 25 50
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Horga LG (2018) Tuning recombinant protein expression to match secretion capacity. in Microbial cell factories

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Morra R (2017) Optimization of Membrane Protein Production Using Titratable Strains of E. coli. in Methods in molecular biology (Clifton, N.J.)

 
Description We have developed technological capabilities to allow us to more effectively produce human therapeutic proteins from bacterial hosts
Exploitation Route Further R&D proposed
Sectors Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology

 
Description Has led to the adoption of new working practices within industrial collaborators UK-based R&D facility, which has led to new business opportunities.
First Year Of Impact 2016
Sector Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology
Impact Types Economic

 
Description EPSRC CDT UCL
Amount £80,000 (GBP)
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Academic/University
Country United Kingdom
Start 10/2015 
End 08/2020
 
Description Enhanced Production and Process Analysis of Biotherapeutics - Antibody Fragments and Alternative Scaffolds
Amount £60,000 (GBP)
Funding ID 1621074 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Academic/University
Country United Kingdom
Start 10/2015 
End 09/2019
 
Description Indonesian Government Home funded PhD Srudenship
Amount £100,000 (GBP)
Organisation Government of Indonesia 
Sector Public
Country Indonesia
Start 09/2016 
End 08/2020
 
Description Synthetic Biology: Development and Application Cellular Computation Devices
Amount £80,000 (GBP)
Funding ID 1618786 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 10/2015 
End 09/2019
 
Description Collaboration with CMO for biologics production 
Organisation Cobra Biologics
Country United Kingdom 
Sector Private 
PI Contribution We have contributed IP, know-how, and research expertise to this collaboration
Collaborator Contribution The partners have contributed industry R&D and know-how
Impact Too earlier to say, the collaboration has led to successful joint grant funding.
Start Year 2013
 
Description Collaboration with International biopharma company (2017- on going) 
Organisation Novo Nordisk
Country Denmark 
Sector Public 
PI Contribution Following on from research data present and US conference, this international biopharma companies made contacted and expressed and expressed an interested in getting access to ort technology and establishing a collaboration
Collaborator Contribution We have discussed and applied a work program together over several months, and executed the appropriate legal agreements. The technical validation work is due to be initiated within Q1 2018
Impact Outputs are still pending.
Start Year 2017
 
Description BBSRC Enterprise Fellowships Networking Event 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact BBSRC Enterprise Fellowships Networking Event
Year(s) Of Engagement Activity 2017
 
Description Croda Open Innovation Day 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact New project ideas discussed.
Year(s) Of Engagement Activity 2017
 
Description EuroScience Open Forum (ESOF) 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact EuroScience Open Forum (ESOF):

+provide an open forum for debate on science and technology and research policies in Europe
+strengthen the links between science and society
+contribute to the creation of an integrated space for science and technology in Europe, linking research organisations and policies at national and EU levels; strive for a greater role of the EU in research and
+influence science and technology policies.
Year(s) Of Engagement Activity 2016
URL http://manchester2016.esof.eu/en/
 
Description FLS Community Open Day 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact An outreach stand about biotechnology for the production of fragrance compounds and public opinion of synthetic biology
Year(s) Of Engagement Activity 2016
 
Description Institute Open Day (Outreach) 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact Synthetic Biology stand at MIB open-day attended by >200 A levels students
Year(s) Of Engagement Activity 2014,2015,2016
 
Description Invited Speaker at Centre of Excellence in Biopharmaceuticals, UK 4th Annual Scientific Symposium 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Participants in your research and patient groups
Results and Impact Q&A

Contact with new potential industrial collaborators
Year(s) Of Engagement Activity 2015
 
Description Invited Speaker at European Congress on Biotechnology 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Participants in your research and patient groups
Results and Impact Q&A

Lead to new contacts
Year(s) Of Engagement Activity 2014
 
Description Invited Speaker at the UK-South Korea Synthetic Biology Workshop. Heathrow UK 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Participants in your research and patient groups
Results and Impact Q&A

New potential collaborators in Korean
Year(s) Of Engagement Activity 2015
 
Description SMART-Map Industrial Dialogue on Synthetic Biology 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Study participants or study members
Results and Impact Workshop on the responsible development of Synthetic Biology which forms part of the EU H2020 SMART-map project.
Year(s) Of Engagement Activity 2017
URL http://projectsmartmap.eu/
 
Description SynBioChem Workshop on Responsible Research and Innovation 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Study participants or study members
Results and Impact Roundtable discussant at SynBioChem Workshop on Responsible Research and Innovation
Year(s) Of Engagement Activity 2015
 
Description iGEM Giant Jamboree 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Synthetic Biology iGEM Giant Jamboree
Year(s) Of Engagement Activity 2016
URL http://2016.igem.org/Giant_Jamboree