Dr S MacNeill, Dr T Gloster
No more applications being accepted
Competition Funded PhD Project (European/UK Students Only)
About the Project
BBSRC Thematic Group: Bioscience for Renewable Resources and Clean Growth
Fructans such as inulins and levans are fructose-based oligo- and polysaccharides derived from sucrose that have found use in a variety of industrial, agricultural and healthcare applications, most notably as prebiotic dietary supplements [1, 2]. Previously, it was thought that fructan biosynthesis was limited to bacteria and plants. However, recent results have for the first time demonstrated fructan biosynthesis by archaeal organisms, specifically halophilic archaea (haloarchaea) [3, 4]. This PhD project will focus on characterising the enzymes and mechanisms of fructan biosynthesis by haloarchaea with a view to establishing new modalities for fructan biosynthesis that can be deployed by industrial biotech.
The haloarchaea are a particularly attractive platform for biotech applications. They are non-hazardous, genetically tractable (allowing facile heterologous gene expression), straightforward to grow in high-salt medium at mesophilic temperatures, and produce enzymes that are active in high salt and generally stable at elevated temperatures [5].
The project will focus initially on haloarchaeal GH68 family fructosyltransferase (FT) enzymes, with four primary objectives: [a] to engineer heterologous expression of evolutionarily diverse haloarchaeal GH68 enzymes in the well-characterised genetically tractable (but non-fructogenic) haloarchaeon Haloferax volcanii, [b] to develop molecular genetic tools allowing regulated high level expression of haloarchaeal GH68 enzymes in their natural host organisms, [c] to purify and characterise in vitro the activities of selected evolutionarily diverse haloarchaeal GH68 enzymes, up to and including protein structure determination by X-ray crystallography, and [d] to utilise the newly developed molecular genetic tools and protocols to analyse the cellular function of GH68 enzymes via reverse genetic approaches.
The project brings together the expertise of the MacNeill lab in culturing and genetically manipulating haloarchaea with the expertise of the Gloster lab in the enzymology and structural biology of carbohydrate processing enzymes. The student will gain experience of molecular microbiology, molecular genetics, bioinformatics, biochemistry and structural biology.
Funding Notes
This project is eligible for the EASTBIO Doctoral Training Partnership: http://www.eastscotbiodtp.ac.uk/
This opportunity is only open to UK nationals (or EU students who have been resident in the UK for 3+ years immediately prior to the programme start date) due to restrictions imposed by the funding body.
Apply by 5.00 pm on 13 April 2020 following the instructions on how to apply at: http://www.eastscotbiodtp.ac.uk/how-apply-0
References
[1] Ahmed and Rashid (2018) Crit. Rev. Food Sci. 59:1.
[2] Tungland (2018) in Human Microbiota in Health and Disease, p. 349-379 (Academic Press).
[3] Kirtel et al. (2018) Biotechnol. Adv. 36: 1524.
[4] Kirtel et al. (2019) Carbohydr. Polm. 220: 149.
[5] Haque et al. (2019) Appl. Micro. Biotech. 104:1371.
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