Prof D G Fernig
Dr I Barsukov
Dr Edwin Yates
Dr M Kapralov
No more applications being accepted
Competition Funded PhD Project (European/UK Students Only)
Polysaccharides could be considered a perfect material for technology to replace most of the oil-based polymers and the drive for green technologies caused by climate change, is encouraging more companies to incorporate them into their products. The goal of this project is to engineer novel polysaccharide modifying enzymes that can be used biotechnologically to develop unique polysaccharide-based materials to replace existing compounds produced using traditional chemical means. We selected sulfation as a universal polysaccharide modification reaction, because it is widely used in nature to create diverse materials in plants and algae, and sulfated molecules are key components of many personal care and food products. We sequenced genomes of several such algae and discovered new enzymes that generate these protective sulfated polysaccharides. In this project you will identify the sulfotransferases across The Tree of Life, as in this new field, even the most basic analyses remain to be done. The activity of these enzymes will be characterized and the crystal structures of the most active ones will be solved. Knowledge of the structure and activity will enable you to design mutations in a high throughput screen that alter enzyme activity so they can accommodate new sulfate acceptor substrates, e.g., polysaccharides of terrestrial plants, and generate new types of polysaccharides that do not occur in nature. The project is multi-disciplinary and will give you opportunity to master a wide range of methods, from genome mining, through protein engineering, structural biology to polysaccharide chemistry.
Work in this project will combine academic research with answering a real-world practical challenge,. You will join a multi-disciplinary team of researchers collaborating in searching for new materials to reduce the environmental impact of existing industrial processes. You will work in different laboratories of Liverpool and Newcastle Universities and in the laboratories of the industry partner, Unilever. Drawing on the complementary expertise of the supervisors’, you will learn a wide range of research methods and use state of the art scientific instruments. Besides science, you will experience life in Liverpool and Newcastle Universities and cities, and in industry. You will participate in outreach activities and learn how to communicate science to the lay public and to develop alternative skills (e.g., entrepreneurship, management, media, ethics) through regular courses and seminars at the Universities. The skills and knowledge gained in the project will be highly valuable for both academic and industrial employment.
HOW TO APPLY
Applications should be made by emailing [Email Address Removed] with a CV (including contact details of at least two academic (or other relevant) referees), and a covering letter – clearly stating your first choice project, and optionally 2nd and 3rd ranked projects, as well as 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.
In addition to the CV and covering letter, please email a completed copy of the Additional Details Form (Word document) to [Email Address Removed]. A blank copy of this form can be found at: https://www.nld-dtp.org.uk/how-apply.
Informal enquiries may be made to [Email Address Removed]
This is a 4 year BBSRC CASE studentship under the Newcastle-Liverpool-Durham DTP. The successful applicant will receive research costs, tuition fees and stipend (£15,009 for 2019-20). The PhD will start in October 2020. Applicants should have, or be expecting to receive, a 2.1 Hons degree (or equivalent) in a relevant subject. EU candidates must have been resident in the UK for 3 years in order to receive full support. Please note, there are 2 stages to the application process.
Structure-based design of nucleoside analogues which inhibit sulfotransferases. RSC Adv. (2019) 9, 32165-32173
Sulfated polysaccharides interact with fibroblast growth factors and protect from denaturation. FEBS Open Bio. (2019) 9, 1477-1487
Heparin binding preference and structures in the fibroblast growth factor family parallel their evolutionary diversification. Open Biol. (2016) 6, 150275
Structural requirements for heparin/heparan sulfate-transforming growth factor-β1 interactions and signal potentiation. Glycobiology 25: (2015) 1491–1504
A systems biology approach for the investigation of the heparin/heparan sulfate interactome. J Biol Chem. (2011) 286, 19892-904
New tools for carbohydrate sulfation analysis: heparan sulfate 2-O-sulfotransferase (HS2ST) is a target for small-molecule protein kinase inhibitors. Biochem J. (2018) 475, 2417-243
Insights into the role of 3-O-sulfotransferase in heparan sulfate biosynthesis. Org. Biomol. Chem., (2017) 15, 6792-6799
1H and 13C NMR spectral analysis of twelve systematically modified heparin derivatives. Carbohydr.Res., (1996) 294, 15-2
Improving recombinant Rubisco biogenesis, plant photosynthesis and growth by coexpressing its ancillary RAF1 chaperone. PNAS 2015, 112(11):3564-9
SHANK3 structure reveals a Ras-associated domain regulating integrin activation. (2016), Nature Cell Biol, 19, 292