Key points:
● 4 year funded programme
● Academia/AstraZeneca collaboration
● Interdisciplinary across molecular and systems biology and bioinformatics
● Gene-expression/RNA biology
The Sudbery (www.sudlab.co.uk) and Wilson labs (https://www.sheffield.ac.uk/biosciences/people/mbb-staff/academic/stuart-wilson) at the University of Sheffield, in collaboration with AstraZeneca (Granta Park, Cambridge) are seeking an enthusiastic PhD student to work on an interdisciplinary project at the confluence of bio-engineering, and synthetic, molecular and systems biology.
Therapeutic proteins such as antibodies are a successful class of biological drugs used to treat a wide range of diseases in areas such as oncology, respiratory, inflammation, autoimmunity and cardiology.
Typically, large‐scale production of such proteins for clinical and commercial therapeutic applications employs stable recombinant mammalian cell lines, such as Chinese hamster ovary (CHO) cells that are transfected with an expression plasmid encoding the antibody genes of interest. High levels of protein expression are key to the successful development and manufacture of these biotherapeutics, and high protein expression is, in part, driven by high expression of the messenger RNA encoding the protein. Much effort has been expended to optimise and control the transcription from these transgenes, such as the use of synthetic promoters and introns in the expression plasmid, but the stability of the transcript and the rate at which it is translated are as important to protein production as optimisation of transcription. RNA stability and translation efficiency are, in turn, controlled by the UnTranslated Region (UTR) transcript regions, in ways that are not fully understood.
The Sudbery lab is primarily interested in how UTR sequences determine transcript fate, and we have developed a machine-learning-enhanced approach to screen the function of hundreds of thousands of synthetic UTR sequences in parallel to identify sequences with desired properties. The successful candidate will apply these approaches to identify and optimise 3’ synthetic UTR sequences for use in the CHO-cell biomanufacturing.
The project will be based in Sheffield and the candidate will also spend at least 3 months over the course of the project with a team at the AZ campus in Granta Park, Cambridge, UK. The candidate will be supported by a well-funded, growing team (2 academic and 1 industrial postdoc) working on related projects. This team is embedded in the supportive, diverse, and international community of PhDs and Postdocs that make up the Sudbery and Wilson labs, and a broader group of RNA labs as part of the Sheffield Institute for Nucleic Acids. They will have unique access to training in cutting-edge molecular, bioinformatic and bio-pharmaceutical approaches. They will leave well qualified for careers both inside and outside academic science.
The ideal candidate would have a good undergraduate or master’s degree in biology, biochemistry or related fields, experience of lab-based molecular biology, a broad and inquiring mind, and a desire to work collaboratively across the experimental, bioinformatic, machine-learning and pharmaceutical disciplines. Previous experience of bioinformatics and machine-learning are not essential, but a comfort with quantitative and statistical thinking is desirable.
This project is funded for 4 years by the BBSRC and AstraZeneca and is open to appropriately qualified candidates from anywhere in the world.
For further details please contact [Email Address Removed].
Applications should be submitted via the University website https://www.sheffield.ac.uk/postgraduate/phd/apply/applying with a closing date of Friday 12th February 2021.
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