Subject areas: Biochemistry / Microbiology / Biotechnology / Biomanufacturing / Bioengineering / Nanotechnology
About the Project
The Department of Biochemical Engineering, UCL, is inviting applications for one full EPSRC Engineering Doctorate (EngD) studentship.
The studentship holder will work under the supervision of Dr Stefanie Frank and Dr Andrea Rayat situated within the Advanced Centre for Biochemical Engineering at UCL. The project is in collaboration with the Vaccines Manufacturing and Innovation Centre (VMIC, at Harwell Campus, Oxford) and will be co-supervised by Dr Martin Smith and Dr Gaurav Gupta.
About:
Virus-like particles (VLPs) and protein nano-compartments have diverse applications in the biomedical and nano-biotechnology fields. Their simple composition and self-assembly properties make them particularly suitable as drug delivery particles and vaccine platforms. Vaccines based on such particles mimic the virus structure for cell uptake and frequently require the display of antigens or handles for modular antigen attachment. These can pose challenges for the expression, assembly and purification of candidates. This studentship aims to address such challenges and develop approaches to optimise the production process of engineered protein-based nanoparticles called encapsulins. Knowledge gained from this project could offer valuable tools that may also be applied to other self-assembling particles like virus-like particles and will expand the search space for novel vaccine candidates.
Project Context and Objectives:
Encapsulin protein nano-compartments are simple prokaryotic organelles that have recently gained interest for biotechnology applications such as targeted drug delivery systems, nano-bioreactors, advanced nano- and biomaterials and for antigen surface display for rational vaccine design. For these and future applications peptides are inserted into the primary capsid protein sequence, for example when engineering particles for direct antigen display. Each new encapsulin variant likely requires optimisation of expression and purification conditions, usually carried out in shake flasks at bench scale. This can be time consuming and sometimes leads to difficult candidates being abandoned. The goals of this studentship are (1) to develop a more systematic, high-throughput approach to optimise expression and purification for protein-based nanoparticles and (2) investigate the potential for large scale production of candidates developed in our lab. To meet these goals the following objectives will be pursued:
· Implementing rapid screening methods and potentially automation for protein expression and clone/strain selection.
· Improving methods for cost-efficient particle purification.
· Investigating the potential for links between encapsulin protein design and quality.
· Small scale fermentation and feasibility of larger scale production of candidates beyond bench scale.
· Investigating potential for methods to be applied to other protein-based nanoparticles such as VLPs.
Outputs and Impacts:
While this project is focused on the development of upstream and downstream processes for engineered encapsulin candidates, methods being developed through this project could offer valuable tools to be applied to other self-assembling protein nanoparticles such as virus-like particles for future vaccine development. Results will be presented at regular meetings with the supervisory team, at conferences and published in peer-reviewed journals.
About UCL Biochemical Engineering:
This project is based in the Department of Biochemical Engineering, a world leader in bioprocess research creating novel engineering solutions to underpin future biomanufacturing processes. The Department delivers research through hubs which are teams of biochemical and system engineers, synthetic biologists and vaccinologists, that work together. This project is aligned with The Future Vaccine Manufacturing Research Hub (Vax-Hub) whose vision it is to manufacture the next-generation vaccines by integrating discovery and bioprocess.
About VMIC:
The candidate will work in collaboration with the UK’s Vaccines Manufacturing and Innovation Centre (VMIC). VMIC seeks to transform vaccine manufacture through intelligent processes and world-leading engineering. Through collaborations like this, VMIC will accelerate development of new and innovative vaccines from discovery to licensed product.
Applicant requirements:
We are looking for candidates with relevant backgrounds, from molecular bioscience to biochemical engineering, with an interest in microbiology, protein biochemistry, fermentation, protein purification, analytics, programming and automation. This project is ambitious and challenging, so applicants must hold a degree equivalent to a UK first class honours, or an upper second-class degree with an aptitude and passion for research.
UCL actively supports equality, diversity and inclusion and encourages applications from all sections of society. We strongly encourage applications from those who are currently under-represented within our research student community: BAME British applicants, applicants with disabilities and older applicants.
The start date for this studentship is 27 September 2021.
How to apply
To apply for this studentship, please send your max. two-page CV and cover letter by email to Dr Stefanie Frank ([Email Address Removed]), project supervisor to arrive no later than 23:59 on Friday, 13th August 2021. In addition to this, you must submit your formal application through UCL’s Application portal for the EngD in Biochemical Engineering and Bioprocess Leadership course for 21/22 entry by 30 July 2021. More information about the application process is available on the department’s website: https://www.ucl.ac.uk/biochemical-engineering/study/postgraduate-research/biochemical-engineering-and-bioprocess-leadership-engd
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