[School of Engineering PhD Scholarships] Recombinant protein production in microalgae

About the project

About the Project The development of microalgae into alternative expression platforms for therapeutic recombinant protein production has long been hampered by the low productivity of protein expression, particularly when nuclear genes are employed. Yield improvements for nuclear proteins are desirable for industrial application as they can be directed down the secretory pathway. Expression of recombinant proteins in the model microalga Chlamydomonas reinhardtii is facilitated by an ever-expanding genetic toolkit, with accompanying strategies to alleviate issues such as transgene silencing and random position effects. These strategies include the development of transgene expression strains UVM4 and UVM11 as well as bicistronic expression constructs that link the gene of interest to a selectable marker gene [1]. Alongside the use of these genetic tools, bioprocess optimisation strategies can be utilised to further drive yield improvements. This study aims to characterise the growth and protein production of C. reinhardtii UVM11 expressing the human protein erythropoietin (EPO) as well as the fluorescent reporter protein mCherry, in both secreted and non-secreted forms [2]. Batch and fed-batch cultivations at a range of scales will be performed, varying initial levels of media nutrients (acetate and nitrogen) as well as light intensity supplied to the culture. A hybrid kinetic model based on Physics-informed Machine Learning techniques will be developed, based on an existing kinetic model developed in the group, to simulate the cultivation process with consideration to nutrient consumption, biomass accumulation, recombinant protein production and the co-production of major algal metabolites (proteins, lipids and starch) [3]. The results from the mixotrophic experiments will provide insights into cultivation of the cell wall-deficient strain UVM11, including general growth characteristics and carbon partitioning of major metabolites; this was found to be affected by whether or not the recombinant protein was secreted or accumulated intracellularly. The predictive capacity of the model will then be exploited to compute an optimal cultivation scenario for the production of recombinant proteins, and these conditions replicated in 12 to 60 PBRs to investigate production at larger scales. If microalgae are to become alternative expression platforms for the biopharmaceutical industry, optimal cultivation strategies that maximise recombinant protein production must be identified. This project is expected to start in September 2027. Before you apply: We strongly recommend that you contact the supervisors for this project before you apply. How to apply: To be considered for this project you must complete a formal application through our online application portal. If you already have an applicant account this link will directly open an application for PhD School of Engineering Scholarships . If you don’t already have an applicant account, please follow the instructions here. . When applying, please specify the full title and supervisor/s of the project, details of your previous study, and names and contact details of two referees. You must also upload a Supporting Statement describing the motivation to apply to the project, your CV and transcripts of awarded and in-progress university qualifications . Please note late or incomplete applications will not be considered. Equality, diversity and inclusion are fundamental to the success of The University of Manchester and central to all our activities. A diverse research community strengthens creativity, productivity and quality, while increasing the societal and economic impact of our work. We welcome applicants from all career paths, backgrounds and sections of the community, regardless of age, disability, ethnicity, gender, gender expression, sexual orientation or transgender status. We welcome applications from candidates returning to study after a career break or experience in other roles. Flexible study arrangements may be available, including part-time study at 50%, 60% or 80%, subject to the requirements of the project and funder. Eligibility : The standard academic entry requirement for this PhD is an upper second-class (2:1) honours degree in a discipline directly relevant to the PhD Chemical Engineering, Biotechnology, Chemistry, Physical Chemistry (or international equivalent) OR any upper-second class (2:1) honours degree and a Master’s degree at merit in a discipline directly relevant to the PhD Chemical Engineering, Biotechnology, Chemistry, Physical Chemistry (or international equivalent). Previous experimental experience and/or computational experience is desirable. This project will remain open until filled. If your application is submitted by 1 st November 2026, you can expect a decision by 18 th December 2026. If your application is submitted by 15 th January 2027, you can expect a decision by 30 th March 2027. Self or externally funded students can also be considered for this project. FSESoE

Research areas