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Iterative automation pipeline for the engineering and characterisation of industrial enzymes


Biosciences Institute

Prof C Harwood , Prof PJ Hussey , Prof A Wipat Friday, January 22, 2021 Competition Funded PhD Project (Students Worldwide)
Newcastle United Kingdom Biochemistry Bioinformatics Biotechnology Genetics Microbiology Molecular Biology Structural Biology

About the Project

The importance of biotechnology is clearly identified in the UK Government’s “Growing the Bioeconomy” policy statement which outlines its power to transform the way we address environmental challenges by developing low carbon bio-based products and processes.

Expertise at Newcastle and Durham Universities, and Procter & Gamble’s (P&G) Newcastle Innovation Centre, will be combined to address bottlenecks in the process of engineering industrial enzymes with specific catalytic and physical characteristics. The student will develop expertise in synthetic and molecular biology, bioinformatics and biochemistry, including production host optimisation, fermentation, and recombinant protein production. The combined expertise of the project supervisory team will equip the student with a diverse and well-rounded set of cutting-edge skills and competences that will provide them with excellent prospects for future employment, either in academia or industry. 

The project is aimed at producing novel proteases for application in laundry detergents that maintain high activities at low temperatures. P&G is committed to developing innovative and sustainable products which reduce environmental pollution and promote responsible consumer behaviours. The P&G Sustainability program Ambition 2030 aims to making a positive impact by accelerated effort towards promoting consumer adoption of colder wash cycles (i.e. 15-20°C) that significantly reduce energy consumption compared to the most selected 40°C cycles.

The project will build on the innovatory approach of multiplexing the production of enzyme variants with a novel assay system that screens their activities. The entire cell-free process will be automated by using laboratory robotics and associated control and analytical software. Once suitable enzymes are identified, the production and assays systems will be scaled up to obtain more detailed information on their enzymatic and physical characteristics. Kinetic and mechanistic studies will provide the basis for the selection of lead compounds for evaluation in laundry detergents. Scaled up production will use Bacillus subtilis, a highly amenable industrial bacterium is capable secretion proteins directly into the culture medium at high yields in excess of 20 g/L.

The PhD programme will be carried out primarily at the Centre for Bacterial Cell Biology (Newcastle University), a world-class research centre with focus on microbiology. Extensive research stays at P&G’s Innovation Centre and Durham University’s Biosciences Department will provide training in applied biocatalysis and mass spectrometry. The project aims to increases the UK's capacity to undertake basic and strategic research in industrial biotechnology through increasing the critical mass of trained staff for careers in universities, research institutes and industry.

Informal enquiries may be made to

HOW TO APPLY 

Applications should be made by emailing with a CV and a covering letter, including whatever additional information you feel is pertinent to your application; you may wish to indicate, for example, why you are particularly interested in the selected project/s and at the selected University. Applications not meeting these criteria will be rejected. We will also require electronic copies of your degree certificates and transcripts.

In addition to the CV and covering letter, please email a completed copy of the Newcastle-Liverpool-Durham (NLD) BBSRC DTP Studentship Application Details Form (Word document) to , noting the additional details that are required for your application which are listed in this form. A blank copy of this form can be found at: https://www.nld-dtp.org.uk/how-apply.


Funding Notes

CASE studentships are funded by the Biotechnology and Biological Sciences Research Council (BBSRC) for 4 years. Funding will cover tuition fees at the UK rate only, a Research Training and Support Grant (RTSG) and stipend. We aim to support the most outstanding applicants from outside the UK and are able to offer a limited number of bursaries that will enable full studentships to be awarded to international applicants. These full studentships will only be awarded to exceptional quality candidates, due to the competitive nature of this scheme.

References

1. Exploring the non-conserved sequence space of Synthetic Expression Modules in Bacillus subtilis. ACS Synth Biol (2018) 7, 1773-1784
2. Secondary metabolite production and the safety of industrially important members of the Bacillus subtilis group. FEMS Microbiology Reviews (2018) 42, 721–738
3. Effect of genome position on heterologous gene expression in Bacillus subtilis: An unbiased analysis. ACS Synthetic Biology, (2016) 5, 942-947
4. Proteomic analysis of Bacillus subtilis strains engineered for improved production of heterologous proteins. Proteomics (2013) 13, 3298-3308
5. Functional Analysis of Enzyme Families Using Residue-Residue Coevolution Similarity Networks. (2019) doi:10.1101/646539.
6. Geometric principles underlying the proliferation of a model cell system. Nat. Commun. (2020) 11, 4149.
7. ShortBOL: A Language for Scripting Designs for Engineered Biological Systems Using Synthetic Biology Open Language (SBOL). ACS Synth. Biol. (2020) 9, 962–966.
8. Plant AtEH/Pan1 proteins drive autophagosome formation at ER-PM contact sites with actin and endocytic machinery. Nature Commun (2019) 10, 5132. doi: 10.1038/s41467-019-12782-6
9. Extracellular DNA Provides Structural Integrity to a Micrococcus luteus Biofilm. Langmuir (2019) 35, 6468-6475. T
10. The Application of a Nuclease Enzyme to Clean Stubborn Soils and Odors in Laundry. J. Surf. Det. (2020) 23, 797-807.


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