Development of scale-down plasmid DNA primary recovery systems and their application to investigate the impact of upstream and downstream process conditions on critical product quality attributes

About the Project

Plasmid DNA(pDNA) is not only a promising biotherapeutic itself but also an essential intermediate product for many in-vivo gene therapeutics. Despite the growing demand for pDNA, there is still much to be uncovered regarding the impact of upstream and downstream process conditions on pDNA purification. High throughput scale-down models are well established in cell culture and downstream protein purification, however the same cannot be said for the purification of pDNA. AstraZeneca have identified the need for high throughput scale-down pDNA purification as an important step in processing. As a result, the project aims to develop a scale-down system focusing on downstream pDNA primary recovery, which will involve:

• Development and characterisation of a scale-down system to investigate the impact of operating conditions and design on primary recovery of pDNA.

• Application of this scale-down purification system to investigate the impact of alkaline lysis conditions on critical product quality attributes with a focus on sc pDNA quality, residual genomic DNA clearance and process yields.

• Investigation of the impact of upstream process conditions on primary recovery performance.

Candidate requirements

Applications are invited from ambitious and self-motivated candidates with a desire to create engineering solutions to address the challenges in biomanufacturing with:

- An MEng/MSc/BEng degree in Biochemical Engineering, Bioprocessing or relevant subject area

- Excellent written, verbal communication and presentation skills in English

- Interpersonal skills and ability to work effectively in a team

- Able to travel between UCL and AstraZeneca (Cambridge, UK) for experimental and research activities if needed.

The successful candidate will be part of the group led by Professor Eli Keshavarz-Moore who are working on plasmid processing design and scale-down/scale-up studies. They will also join the UCL-AstraZeneca CoE team of PhD and postdoctoral researchers working across upstream and downstream processing. There is an expectation that the successful candidate may spend time at the industrial sponsor site (AstraZeneca – Cambridge, UK) as required for the completion of project deliverables, under the supervision of the Industrial Supervisors: Will Bryan-Smith, Dr Tingting Cui (AstraZeneca, UK) and Mark Berge (AstraZeneca, USA).

The successful candidate joins a cohort of engineering doctorate students in UCL’s award-winning EPSRC Centre for Doctoral Training in Bioprocess Engineering Leadership. The EngD provides ample opportunities to gain skills and adopt tools which are widely applicable in the commercialisation of biotechnology products. Specifically, in this project, the successful candidate will gain skills in such areas as:

- Downstream purification techniques (lysis, filtration, FPLC)

- Scale-down system development and optimisation

- Analytical techniques (HPLC, agarose gel, CGE, PCR)

- Cell culture techniques (transformation, selection, HT-bioreactor operation)

- Exposure to industrial lab environment and operating practices

- Laboratory automation, experimental design, and database management

- Pilot plant experience.

Additional information about research in the Biochemical Engineering department at UCL can be found at https://www.ucl.ac.uk/biochemical-engineering/

Entry requirements

A UK Master’s degree, or a minimum of an upper second-class UK BEng/Meng degree, in a relevant engineering discipline, or an overseas qualification of an equivalent standard.

Deadline and Application Process

The deadline for submission is 20 May 2022 (23:59 BST)

Please send a CV (max 2 pages) and covering letter outlining motivations for undertaking this EngD studentship and relevant experience and expertise. Please send this directly to Prof Eli Keshavarz-Moore ([Email Address Removed]) quoting ‘UCL-AstraZeneca EngD’ in the subject of the email.

Candidates will be contacted via email for interview.

In addition to this you must submit your formal application to the Research Degree: DDNBENSING01 EngD in Bioprocess Engineering Leadership course through UCL’s application portal by the above deadline. More information about the course and application process is available here: https://www.ucl.ac.uk/prospective-students/graduate/researchdegrees/biochemical-engineering-bioprocess-leadership-engd.