Manipulation of tRNA to Enhance Biologic Production
Lead Research Organisation:
University of York
Department Name: Biology
Abstract
Biologic production is a multibillion dollar industry, providing substantial healthcare benefits and unlimited opportunity for expansion. Funded by a BBSRC Industrial Biotechnology Catalyst Early Stage Translation Award, my lab developed a novel synthetic biology strategy that boosts product quality and yield in proof-of-principle experiments. Follow-on funding is sought to support conclusive tests of our strategy using proprietary platforms and biologics under conditions of industrial production, in collaborations with multinational companies.
Our strategy is based on measuring and manipulating tRNAs required for biologic synthesis. Some tRNAs are much more abundant than others and scarcity of a single tRNA can restrict production. However, relative levels of tRNAs have not been measured in industrial contexts. We propose to fill this key knowledge gap and remediate deficiencies by tRNA supplementation and improved codon optimization.
Our strategy is based on measuring and manipulating tRNAs required for biologic synthesis. Some tRNAs are much more abundant than others and scarcity of a single tRNA can restrict production. However, relative levels of tRNAs have not been measured in industrial contexts. We propose to fill this key knowledge gap and remediate deficiencies by tRNA supplementation and improved codon optimization.
People |
ORCID iD |
Robert White (Principal Investigator) |
Description | We have found a significant depletion of tRNA when bioreactors are used to produce biopharmaceuticals. Not all tRNAs are depleted equally and a minority buck the trend completely. The changes are likely to hamper productivity. |
Exploitation Route | Steps can be taken to restore tRNA expression &/or to adapt codon usage for better use of limiting tRNAs |
Sectors | Pharmaceuticals and Medical Biotechnology |
Description | Optimisation of CHO for Biotherapeutic Manufacture |
Amount | £3,608,961 (GBP) |
Funding ID | EP/V038095/1 |
Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
Sector | Public |
Country | United Kingdom |
Start | 09/2021 |
End | 09/2026 |
Description | FDBK studentships |
Organisation | Fujifilm |
Department | Fujifilm Diosynth Biotechnologies, UK |
Country | United Kingdom |
Sector | Private |
PI Contribution | White, Bryant & Ungar as supervisors and co-supervisors |
Collaborator Contribution | Studentships awarded to FDBK as a Collaborative Training Partnership. |
Impact | No outputs yet |
Start Year | 2020 |
Description | Fujifilm Diosynth Biotechnologies Centre of Excellence in Bioprocessing 2.0 |
Organisation | Fujifilm |
Department | Fujifilm Diosynth Biotechnologies |
Country | United States |
Sector | Private |
PI Contribution | I lead the bid from University of York to join this partnership |
Collaborator Contribution | My staff have been conducting tests in FDB laboratories, using their equipment and reagents |
Impact | Ongoing. |
Start Year | 2019 |
Description | Prosperity Partnership |
Organisation | Fujifilm |
Department | Fujifilm Diosynth Biotechnologies, UK |
Country | United Kingdom |
Sector | Private |
PI Contribution | We are actively contributing to four of the five work packages. |
Collaborator Contribution | FDBK are the Industrial partners. Additional academic partners are the universities of Edinburgh (lead) and Manchester. |
Impact | No outputs yet. |
Start Year | 2021 |
Description | Fujifilm Diosynth Biotechnologies Centre of Excellence in Bioprocessing 2.0 |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Industry/Business |
Results and Impact | Ongoing collaboration involving industrial partner Fujifilm Diosynth Biotechnologies UK and the Universities of Edinburgh, Manchester and York. |
Year(s) Of Engagement Activity | 2019,2021,2022 |