BBSRC White Rose DTP CASE Studentship - Synthetic Biology-Based Polymerase and Promoter Engineering for Production of Next-Generation mRNA Therapeutics

A fully funded BBSRC-AZ CASE PhD studentship is available in the Department of Chemical and Biological Engineering at the University of Sheffield, starting in October 2023.

The therapeutic promise of mRNA-based biopharmaceuticals was realised when they formed the backbone of the world’s vaccination programme against Covid-19. Beyond vaccines, they also have application in gene therapy, offering potential to treat many currently incurable conditions including cancer, neurological disorders and cardiovascular diseases. However, much is still unknown regarding how the fundamental components of mRNA manufacturing systems (the RNA Polymerase and DNA template) mechanistically interact to determine product yield and quality. This is particularly true for the next-generation of mRNA therapeutics that are substantially larger and more complex than previously studied mRNA products. These products offer potential to improve patient outcomes by delivering enhanced therapeutic efficacies at reduced doses. However, we currently lack the required tools to optimise manufacture of these ‘difficult-to-produce’ molecules.

In this collaborative project with AstraZeneca, we will use a synthetic biology approach to design new biological components for production of next-generation mRNA therapeutics. This will include core synthetic biology techniques such as DNA sequence design, directed evolution of proteins, high-throughput screening of biological systems, bioanalytics, and machine learning. Specifically, the project has the following objectives:

i) Understand how RNA polymerase and promoter sequence features govern their ability to produce large, complex mRNA molecules.

ii) Design and test libraries of novel, synthetic RNA polymerase-promoter pairs.

iii) Design and engineer an RNA polymerase-promoter system that is specifically optimised to manufacture next-generation products at high yields, reduced cost and enhanced quality.

This is an excellent opportunity for a postgraduate student who is passionate about synthetic biology and keen to make a positive contribution to a project with direct bioindustrial application. The student will join an active research group (20+ members) with extensive industry-links, working at the cutting edge of biopharmaceutical development, design and manufacture. Working in our molecular biology, bioanalytical, microbial and cell culture laboratories, equipped with up-to-date industrially-relevant technologies/equipment, the student will obtain skills and capabilities that are in high-demand in both academia and the biopharmaceutical/biotechnology industry. The student will carry out a research placement at AstraZeneca and will receive an enhanced stipend (£20,668 PA). If you require any further information before making an application, please contact Dr Adam Brown ([Email Address Removed]) or Prof Tuck Seng Wong ([Email Address Removed]).

The BBSRC WR DTP and the University of Sheffield are committed to recruiting future scientists regardless of age, ethnicity, gender, gender identity, disability, sexual orientation or career pathway to date. We understand that commitment and excellence can be shown in many ways and we have built our recruitment process to reflect this. We welcome applicants from all backgrounds, particularly those underrepresented in science, who have curiosity, creativity and a drive to learn new skills.

Entry Requirements: The ideal candidate will have (or expect to obtain) a first or upper second class degree (or equivalent) in a relevant discipline such as biology, molecular biology, biochemistry, biotechnology, bioengineering or chemical engineering (with a biology-based specialism).

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Programme: PhD in Mechanistic Biology (4 Years)

Start Date: 1st October 2023