PhD Studentship - Application of Engineering Biology to Enhance Recombinant Antibody Manufacture by Chinese Hamster Ovary (CHO) Cells

Research theme: Biotechnology, Molecular Biology, Bioprocessing

How many PhD project positions: one

How to apply: uom.link/pgr-apply-2425

Studentship funding is agreed for 3.5 years and covers tuition fees at home rate only and an annual stipend at the standard UKRI rate. The funding is provided by the University of Manchester and FUJIFILM Diosynth Biotechnologies. This award does not include any costs associated with relocation. The studentship is for UK students.

You will develop and implement a synthetic biology-based inducible system for expression of recombinant antibodies (rmAbs) in Chinese hamster ovary (CHO) cells. Applying the methods of engineering biology to CHO cells as a chassis organism will provide a cost-effective and efficient method for controlling rmAb production, cell metabolism and growth, leading to high-level yields without the drawbacks associated with traditional small molecule inducers of expression.

The project is designed with 3 work packages

SO1. Design and construction of the inducible system (vectors and CHO cell variant).
SO2. Evaluation of gene expression of rmAbs using control and inducible conditions.
SO3. Evaluation of the metabolic modulation of mammalian cells and specific metabolic gene targets under induction.

The ultimate vision is the development of an inducible cell platform capable of inducing recombinant gene expression, enabling process development in an industrially-based manufacturing environment. The work is part of an on-going collaboration between the Dickson lab (and other staff at the Universities of Manchester, Edinburgh and York) and FUJIFILM Diosynth Biotechnologies (fujifilmdiosynth.com/knowledge-center/resource-library/centre-of-excellence-in-bioprocessing-first-cohort-of-phd-graduates). The work programme will offer the potential for a placement to be undertaken within the laboratories of FUJIFILM at Billingham, where mid/large-scale bioreactors will be used to confirm the expectations generated from the small-scale technical developments generated at the University of Manchester.

This project offers the opportunity to apply cutting-edge engineering biology techniques to the development of inducible expression systems that reflect the needs for the manufacture of rmAbs for the next decade. You will master a toolbox of research skills (technical, communication and personal) that will form a unique launching point for your career development.

Background publications:

Torres, M, Hawke, E, Hoare, R, Scholey, R, Pybus, L, Young, A, Hayes, A & Dickson, AJ (2024) “Deciphering molecular drivers of lactate metabolic shift in mammalian cell cultures” Metabolic Eng. Accepted 02/12/24.

Pennington, O, Torres, M, Dickson, AJ & Zhang, D (2024) “A multiscale hybrid modelling methodology for cell cultures enabled by enzyme-constrained dynamic metabolic flux analysis under uncertainty” Metabolic Eng. 86: 274-287.  

Hussain, H, Ozanne, AMS, Patel, T, Vito, D, Ellis, M, Hinchliffe, M, Humphreys, DP, Stephens, PE, Sweeney, B, White, J, Dickson, AJ & Smales, MC (2024) “Sequence and Configuration of a Novel Bispecific Antibody Format Impacts its Production using Chinese Hamster Ovary (CHO) Cells” Biotechnol. Bioeng. doi.org/10.1002/bit.28879

Torres, M, Mcconnaughie, D, Akhtar, S, Gaffney, CE, Fievet,, B, Ingham, C, Stockdale, M & Dickson, AJ (2024) “Enginering mammalian cell growth dynamics for biomanufacturing” Metabolic Eng. 82: 89-99.

Applicants should have, or expect to achieve, at least a 2.1 honours degree or a master’s (or international equivalent) in a relevant science or engineering related discipline.

Before you apply, please contact Prof. Alan Dickson at alan.dickson@manchester.ac.uk. Please include details of your current level of study, academic background and any relevant experience and include a paragraph about your motivation to study this PhD project.

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