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
Horga LG
(2018)
Tuning recombinant protein expression to match secretion capacity.
in Microbial cell factories
Kent R
(2018)
Rationalizing Context-Dependent Performance of Dynamic RNA Regulatory Devices.
in ACS synthetic biology
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. The outcomes from this award have lead to further project entitle, Plasmid Copy Control - Enhanced pDNA Manufacture for Gene and Immunotherapy, in collaboration with a UKbased CMO, funded by a BBSRC IAA (BB/S506692/1) |
| Sector | Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology |
| Impact Types | Economic |
| Description | BBSRC IAA The University of Manchester |
| Amount | £300,000 (GBP) |
| Funding ID | BB/S506692/1 |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 03/2018 |
| End | 03/2021 |
| Description | Cellulosomes - a versatile enzymatic scaffold platform for bioconversion of lignocellulosic biomass into value-added fine chemicals |
| Amount | £50,000 (GBP) |
| Organisation | São Paulo Research Foundation (FAPESP) |
| Sector | Public |
| Country | Brazil |
| Start | 04/2019 |
| End | 04/2020 |
| Description | EPSRC CDT UCL |
| Amount | £80,000 (GBP) |
| Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
| Sector | Public |
| 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 | Public |
| 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 | Plasmid Copy Control - Enhanced pDNA Manufacture for Gene and Immunotherapy |
| Amount | £50,000 (GBP) |
| Funding ID | n/1 |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 02/2020 |
| End | 07/2020 |
| Description | Responsive Mode |
| Amount | £623,000 (GBP) |
| Funding ID | BB/T005742/1 |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 12/2020 |
| End | 06/2024 |
| 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 | Private |
| 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 | Collaboration with the c (CPI) |
| Organisation | Centre for Process Innovation (CPI) |
| Country | United Kingdom |
| Sector | Private |
| PI Contribution | The aim to better understand the process parameter associated with an unexpected excretion phenotype from bacterial cells. We provide stains and protocols. |
| Collaborator Contribution | Access to facilities and advice on process validation and scale up. |
| Impact | Too early |
| Start Year | 2019 |
| 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 |