Clone of Postgraduate funded projects and scholarships

The use of vaccines prevents the death of nearly 3 million people each year. However, continuous innovations are essential to overcome persistent challenges in reaching a global vaccination programme. These challenges encompasses limitations in the manufacturing capacity, distribution and ultimately the cost of vaccines. The manufacturing of vaccines relies on the use of batch operations in large facilities requiring highly skilled operators, which concomitantly contribute significantly the total vaccine costs. The limitations in manufacturing technologies are nowadays clearly visible with our reduced ability to respond to the COVID-19 pandemic quickly and efficiently.

In particular, mRNA technology is showing potential to be an alternative to traditional vaccines and plasmid DNA-based therapies. These small molecules are ideal vaccine candidates since they are none infectious, integrative and are readily degradable by the cellular mechanism. mRNA is precise as it will only express a specific antigen and induces a directed immune response (humoral and cellular) without the aid of adjuvants. The manufacturing of these molecules is highly flexible, standardised and since the production is based on the in vitro transcription reaction is performed using a DNA template and RNA polymerase, safety concerns can be low due to the absence of cell-derived impurities or viral contaminations. However, the lack of a scalable and cost-effective manufacture process that consistently delivers a high-quality product compromises the application of mRNA-based therapies.

To achieve this aim, miniaturized continuous-flow reactors are prime candidates as a production platform. Their small dimensions allow experiments to be performed with much smaller volumes compared to traditional batch systems, offering significant cost reduction when using expensive substrates or enzymes. Within these reactors the control of reaction parameters is facilitated, and in-line purification with recovery of products has been demonstrated. Additionally, reactions can be potentially accelerated due to enhanced mass transfer with a concomitant decrease in reaction time. Therefore, miniaturized continuous-flow reactors will in the future form the basis to acquire high-quality data rapidly, allowing scalable and cost-effective manufacture platform for mRNA-based therapies to be established.

Project Objectives

Development of a production process for 5’ capped mRNA using, for example, RNA polymerase and vaccinia capping enzyme complex immobilized in miniaturized continuous-flow devices.
Design, fabricate, and characterize scalable purification processes (e.g. tangential flow filtration or multimodal chromatography units) to obtain 5’ capped mRNA free from reaction components and malformed mRNA.
Assembly and validation of a continuous bioprocess sequences of the mRNA manufacture process using miniaturized continuous-flow devices.

Output & Impact

This project aligns with UK strategic priorities in the area of Industrial Biotechnology and the departmental EPSRC Future Biomanufacturing Research Hub, EPSRC Future Vaccine Manufacturing Research Hub and EPSRC Future Targeted Healthcare Manufacturing Hub. Due to the high relevance and timeliness of this research direction, we anticipate that each objective of the project will lead to a publication output. The results obtained throughout this project will be included in teaching of undergraduates or postgraduate modules.

Applications

Applicants should have a degree equivalent to a UK first class honours, or a high upper second class, in Engineering or Physical Sciences. This PhD will be multidisciplinary, straddling both biochemical and chemical engineering. The successful candidate should have strong analytical skills and aptitude for molecular biology, biocatalysis, and reactor engineering.

The starting date for this PhD will be 28 September 2020. To apply for this studentship, please send your max. two-page CV and cover letter by email to Dr Marco Marques, project supervisor to arrive no later than 12pm on Monday, 13th July 2020. In addition to this, you must submit your formal application through UCL’s Application portal for the Research Degree: Biochemical Engineering course for 20/21 entry. More information about the application process is available on the department’s website: www.ucl.ac.uk/biochemical-engineering/study/postgraduate-research/biochemical-engineering-mphilphd

The University actively supports equality, diversity and inclusion and encourages applications from all sections of society.

Funding Notes

This research project has funding attached. It is only available to UK citizens or EU citizens. The studentship covers the full cost of UK/EU tuition fees, plus a tax free stipend for four years. Annual stipend for 20/21: £17,285.

Readying Miniaturized Reactors for Flow Biocatalysis

Project supervisor: Dr Marco Marques
Course: Research Degree: Biochemical Engineering [RRDBENSING01]
Proposed start date: 1 February 2021
Application deadline: 8 January 2021

About the Project

In almost all engineering sectors there has been a successful transition from batch to continuous processing. One particularly promising area for continuous processing in biochemical engineering is the biocatalytic synthesis of active pharmaceutical ingredients (APIs) and value-added chemicals. However, continuous production at large scale has not yet been successfully demonstrated. Continuous-flow biocatalysis offers an improved control over reaction conditions with benefits in yield and productivity levels. This increase in efficiency and concomitantly minimization of waste will ultimately result in cleaner processes with lower overall costs. Furthermore, continuous processes enable a reduction in process lines and facility footprints which in turn result in less up-front capital investment. To exploit the full benefits of continuous processing, it is necessary to characterise reactor performance, and to understand the interplay between the biocatalysts’ constraints and the reactor operation. Only then can these processes be exploited to successfully at industrially relevant volumes.

To achieve this aim, scale-down models that enable careful assessment of reactor performance and biocatalysts’ behaviour are necessary. Miniaturized continuous-flow reactors are prime candidates. Their small dimensions allow experiments to be performed with much smaller volumes compared to traditional batch systems, offering significant cost reduction when using expensive substrates or enzymes. Within these reactors the control of reaction parameters is facilitated, and in-line purification with recovery of products has been demonstrated. Additionally, reactions can be potentially accelerated due to enhanced mass transfer with a concomitant decrease in reaction time. Therefore, miniaturized continuous-flow reactors will in the future form the basis to acquire high-quality data rapidly and with high throughput.

Project Objectives

• Design, fabricate, and characterize a miniaturized continuous-flow reactor with integrated optical sensors and at-line analytical tools for the on-line monitoring of chemical and physical variables (pH, temperature, oxygen and CO2) and for at line reaction analytics (GC- and LC-MS).

• Validate the integrated miniaturized continuous-flow reactor with industrially relevant biocatalytic reactions.

• Compare the reactor performance in batch and continuous systems (e.g. by space-time yields, (gproduct/(Lreactor.h), and (gproduct/genzyme)) at all scales assessing process stability, quality profile of the products process and scalability.

Output & Impact

This project aligns with UK strategic priorities in the area of Industrial Biotechnology and the departmental EPSRC Future Biomanufacturing Research Hub. Due to the high relevance and timeliness of this research direction, we anticipate that each objective of the project will lead to a publication output. The results obtained throughout this project will be included in teaching of undergraduates or postgraduate modules.

Applications

Applicants should have a degree equivalent to a UK first class honours, or a high upper second class, in Engineering or Physical Sciences. This PhD will be multidisciplinary, straddling both biochemical and chemical engineering. The successful candidate should have strong analytical skills and aptitude for biocatalysis, reactor engineering and numerical modelling.

The starting date for this PhD will be 1 February 2021. To apply for this studentship, please send your max. two-page CV and cover letter by email to Dr Marco Marques, project supervisor to arrive no later than 12pm on Friday, 8 January 2021. In addition to this, you must submit your formal application through UCL’s Application portal for the Research Degree: Biochemical Engineering course for 20/21 entry by the above deadline.

The University actively supports equality, diversity and inclusion and encourages applications from all sections of society.

Funding Notes

Scholarships and prizes

UCL Graduate Research Scholarship (GRS)

The scholarship covers UK rate fees and maintenance stipend. Please submit the complete application pack to Andrea Crammond (a.crammond@ucl.ac.uk) by 13 January 2021 if you would like to be considered for shortlisting. More information: https://www.ucl.ac.uk/scholarships/graduate-research-scholarships

UCL Overseas Research Scholarship (ORS)

The scholarship covers the difference between UK and Overseas tuition rate fees and may be held alongside the UCL Graduate Research Scholarship. Please submit the complete application pack to Andrea Crammond (a.crammond@ucl.ac.uk) by 13 January 2021 if you would like to be considered for shortlisting. More information: https://www.ucl.ac.uk/scholarships/overseas-research-scholarships

UCL Engineering Dean’s Prize

The Dean's Prize supports overseas fee-paying students who have won a competitive scholarship to cover their stipend, by waiving the international fees. Please submit the complete application pack to deans.prize@ucl.ac.uk by 20 January 2021 if you would like to be considered for shortlisting. More information: https://www.ucl.ac.uk/scholarships/deans-prize.

UCL-CSC (China Scholarships Council) Scholarships

Funding offered by UCL and the China Scholarships Council (CSC) aims to expand the educational, cultural and technological co-operation between the UK and China. The CSC provides economy air travel to and from the UK, a living allowance and visa application fees. UCL will provide full tuition fees for the standard duration of a full-time MPhil/PhD programme up to 48 months, including a writing-up period. May be held alongside the UCL Overseas Research Scholarship or the Engineering Dean’s Prize. Please submit the complete application pack to Andrea Crammond (a.crammond@ucl.ac.uk) by 13 January 2021 if you would like to be considered for shortlisting. More information: https://www.ucl.ac.uk/scholarships/china-scholarship-council-ucl-joint-research-scholarship

Clone of Postgraduate funded projects and scholarships

Current Funded PhDs and EngDs

About the Project

Project Objectives

Output & Impact

Applications

Funding Notes

Scholarships and prizes

UCL Graduate Research Scholarship (GRS)

UCL Overseas Research Scholarship (ORS)

UCL Engineering Dean’s Prize

UCL-CSC (China Scholarships Council) Scholarships

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