Multiscale modelling and experimental analysis of protein stability in biopharmaceutical processing

There is an opportunity for a fully-funded combined 1-year MRes and 3-year PhD studentship in the EPSRC Centre for Doctoral Training in Sensor Technologies and Applications for an Uncertain World (Sensor CDT), for a student eligible for Home Fees at the University of Cambridge. This studentship will be funded by the industrial partner, AstraZeneca, and Corpus Christi College and will start in October 2025.

Applications should be made using the Application Portal by the deadline of 20 June 2025.

The application portal is open for applications to this studentship only.

The studentship

The studentship includes the University Fees, a stipend (at the UKRI level, which usually increases annually and is not subject to UK income tax or national insurance), and a Research Training and Support Grant (for other training costs, such as attending a conference). The candidate will be a member of the Sensor CDT and take part in all the activities and opportunities. The successful candidate will be admitted to Corpus Christi College.

The MRes in Sensor Technologies and Applications supports the development of advanced, graduate-level knowledge and research skills with taught and research modules.

The PhD research will create a new level of understanding about how complex biological molecules are influenced during fluid flow by shear forces, pressure fluctuations, surface interactions, and changes in formulation conditions. This critical area will enable the development of sensor technologies that help translate future therapies to advanced manufacturing techniques. This interdisciplinary project allows candidates to broaden their skill base, and build in-depth capabilities in simulation, experimental and characterisation-based research.

The project will take place in labs in the Department of Chemical Engineering and Biotechnology, labs in the next-door building Institute for Manufacturing, Department of Engineering and AstraZeneca, Cambridge.

Research project summary

Biopharmaceuticals are biological molecules manufactured by or from living organisms using bioprocessing techniques, explicitly for the prevention, treatment and diagnosis of diseases. Protein-based therapeutics, including monoclonal antibodies, enzymes, polyclonal antibodies and hormones are the dominant product category within the biopharmaceutical industry. There is an increasing need to turn to biopharmaceuticals for rare disease treatments, for biologic vaccines to tackle pandemics and because of their potential for targeted molecular therapies, for example, to treat cancer.

However, proteins are large, complex molecules where the final folded structure is a key element in determining the function. When manufacturing these complex therapeutics, they experience multiple processing steps, including mixing, dilution, pumping and filtration, that expose them to mechanical, chemical and environmental stresses. These include shear forces, pressure fluctuations, surface interactions with a range of different materials, and changes in formulation conditions. All of these can influence protein structure, stability, aggregation and processability.

To address these challenges, this PhD research project will explore mechanistic insights into how proteins respond to hydrodynamic stress, material interactions and environmental variations during biopharmaceutical processing. This will involve multi-scale computational modelling to link fluid flows to changes in molecular behaviour for industrially-relevant flows. Next, the candidate will use these insights to develop experimental research to examine real flows found in industrial processing, with sterile filtration as a particular case study because of its challenges.

The impact of this work will be the creation of a framework that bridges underpinning science and molecular design with manufacturing engineering to accelerate innovation in complex new therapeutics.

Supervision

The research is supported by AstraZeneca and supervised by:

• Shelly Singh-Gryzbon: Assistant Professor in the Department of Chemical Engineering and Biotechnology, focusing on fundamental engineering principles, such as fluid dynamics and structural mechanics, leveraging computational simulations to inform the design, development and optimisation of medical devices and therapies to tackle clinically relevant problems.
• Ronan Daly: Professor of Advanced Manufacturing in the Department of Engineering, focusing on fundamental research into fluids, interfaces, biomaterials, nanomaterials and chemical systems that support the future of advanced manufacturing, with a focus on driving affordability, accessibility, and environmental sustainability.

Candidate background

Applications are encouraged from those with Chemical Engineering, Mechanical Engineering, Materials Science, Chemistry or Physics backgrounds, or similar degrees where there is a good understanding of fluid mechanics and thermodynamics. A knowledge of proteins and biopharmaceuticals is welcome but not essential, and the candidate will be supported in learning about these topics within the programme.

Candidates must be eligible for Home Fees. Previous applicants to the Sensor CDT for this academic year need not apply.