Funding

Funded PhD Project (UK and EU students only)

Project code

BIOL5170220

Department

Centre for Enzyme Innovation, School of Biological Sciences

Start dates

Closing date

7 February 2020

This project is now closed. The details below are for information purposes only. View our current projects here.

Applications are invited for a fully-funded four year PhD studentship to commence in October 2020.

The PhD will be based at the Centre for Enzyme Innovation (CEI), and will be supervised by Dr Bruce Lichtenstein, Prof. John McGeehan and Dr Sam Robson
Established in 2019, the CEI focuses on the discovery, engineering and deployment of new enzymes to accelerate advances in the circular economy -- with a focus on degradation of synthetic polymers and plastics and reuse of their component monomers.

The recent identification of microbial enzymes capable of degrading the commonly used plastic poly(ethelene terephthalate,) PET -- found in water bottles, food containers, and clothing -- highlights the potential for the engineering and application of enzymes to address some of our biggest environmental challenges. PET degrading enzymes have been identified from multiple evolutionary lineages, suggesting a rather ancient activity unrelated to our modern mass production of PET plastics. The goal of this project is to apply these deep evolutionary relationships in the design of promiscuous polyester degrading enzymes, and to pursue in vitro evolutionary experiments (directed evolution) to refine this activity and explore the engineering and protein structural determinants governing their function. 

The studentship is available to UK and EU students only and covers tuition fees and an annual maintenance grant of £15,009 (UKRI 2019/20 rate) for three years. University funding will be made available to offer extensions into a 4th year where this will maximise scientific output and boost research careers.  Funds of £7,500 per annum are available to cover research expenses and support attendance at workshops and conferences.

The work will include:

  • Engineering promiscuous esterases using deep evolutionary relationships of known PET degrading enzymes
  • Directed evolution and protein engineering to improve enzymatic activity on real-world substrates
  • Analysis of and modelling from NGS deep sequencing data on selected libraries to define engineering principles that govern improved activity
  • Characterization of isolated novel esterases using standard and newly developed biophysical techniques
  • Structural characterisation (using X-ray crystallography) of new hydrolase designs
  • Interfacing with additional team members to integrate improved enzymes into industrial and metabolic processes

This project brings together expertise within the Centre for Enzyme Innovation with the common goal of addressing two imminent, and interrelated global challenges: plastic pollution and re-use of refined, often petroleum derived, carbon-based materials. Everyday plastics such as poly(ethylene terephthalate), or PET, are highly versatile but the chemical properties that make them so useful also make them highly resistant to natural biodegradation. But there is hope: enzymes that can digest PET-- albeit with limited kinetics -- have already been identified in a variety of different, unrelated organisms [1-5].

The natural breadth of organisms that host enzymes that can process PET suggests that the activity for poly-ester degradation is much older than the five decades PET plastics have been produced by humanity. Modern enzymes have evolved to efficiently process a limited set of substrates, and their poor activities seen in the digestion of PET plastics may reflect an evolutionary process that moved away from ancient hydrolase enzymes that had more promiscuous and robust activity for polyester degradation. 

Using the techniques of ancestral reconstruction, we will reverse this evolutionary process to identify ancient hydrolases capable of digesting modern PET plastics. These new hydrolases will then serve as the starting point for directed evolution towards a refined PET degradation activity. By stepping back to antecedent enzymes, this process will allow us to control an evolutionary trajectory unmarred by competing evolutionary processes in biology. Using deep sequencing of the evolving library of PETases, we will identify sequence characteristics of enzymes capable of binding to and digesting plastic surfaces. Coupling these discoveries with biophysical and structural characterization of isolated new PETases will allow us to establish engineering requirements for enzymes capable of processing a wider array of plastics. 

The successful applicant will join a growing group of diverse scientists at the recently established Centre for Enzyme Innovation (CEI).In addition to the full program of training provided by the university’s Graduate School, specialist training will be provided for a range of in-house instruments and techniques, including a full complement of biophysics, structural biology, and next generation sequencing instrumentation. In addition, the project will provide the student with many opportunities to develop new techniques in the selection, evolution, and evaluation of plastic degrading enzymes.

References

  1. Araújo, R. et al. Tailoring cutinase activity towards polyethylene terephthalate and polyamide 6,6 fibers. J. Biotechnol. 128, 849–857 (2007).
  2. Müller, R.-J., Schrader, H., Profe, J., Dresler, K. & Deckwer, W.-D. Enzymatic Degradation of Poly(ethylene terephthalate): Rapid Hydrolyse using a Hydrolase from T. fusca. Macromol. Rapid Commun. 26, 1400–1405 (2005).
  3. Zheng, Y., Yanful, E. K. & Bassi, A. S. A review of plastic waste biodegradation. Critical Reviews in Biotechnology 25, 243–250 (2005).
  4. Yoshida, S. et al. A bacterium that degrades and assimilates poly(ethylene terephthalate). Science. 351, 1196–1199 (2016).
  5. Austin, H. P. et al. Characterization and engineering of a plastic-degrading aromatic
    polyesterase. Proc. Natl. Acad. Sci. 115, E4350–E4357 (2018).
 

Entry requirements

Entry requirements

The project requires a candidate with a good first degree (minimum 2.1 or equivalent) in biochemistry or a related subject, and a desire to excel as a disciplined scientist within a cohesive research team.  Potential applicants with a Masters-level qualification, or equivalent experience in a relevant field, are strongly encouraged to apply.  

English language proficiency at a minimum of IELTS band 6.5 with no component score below 6.0.

We are looking for a talented student with a strong background in Biochemistry, Chemical Biology, Biophysics and/or Structural Biology.

How to apply

We’d encourage you to contact Dr. Bruce Lichtenstein on bruce.lichtenstein@port.ac.uk or Prof. John McGeehan on john.mcgeehan@port.ac.uk to discuss your interest before you apply, quoting both the project code and the project title. For administrative and admissions enquiries please contact cei@port.ac.uk.

When you are ready to apply, you can use our online application form making sure you submit a personal statement, proof of your degrees and grades, details of two referees, proof of your English language proficiency and an up-to-date CV. 

Our ‘How to Apply’ page offers further guidance on the PhD application process. 

If you want to be considered for this funded PhD opportunity you must quote project code BIOL5170220 when applying.

Interview date: Week commencing Monday 2nd March 2020   

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