Bacterial adaptation to changing conditions is commonly investigated over long timescales (evolution of species/lineages), focusing on strong pressures provided by toxic substances (antimicrobials) or predators (bacteriophages/macrophages). However, new bacterial niches emerge through anthropogenic shaping of the environment and include exposure to new energy sources. To understand such bacterial adaptation, relevant to macroscopic events that include climate change or flooding events, it is essential to correlate them with the molecular mechanisms involved.
We will exploit our already established protocols to synthesize novel polysaccharides (NPs; structures not found in nature) to understand how a model bacterial community evolves to utilise a new energy source. There are three aims:
1) Bacterial growth on NPs comprising both entirely novel and minor modifications of existing polysaccharide energy sources; testing mono-cultures and communities. This minimises risk by providing opportunities to study both gradual adaptation (increasing selection), or sharp changes (evolutionary bottleneck) using a broad spectrum of in-house bacterial isolates (Bacteroidetes; ~30 species), many of which possess extensive carbohydrate processing machinery.
2) Whole genome sequencing will reveal the genetic adaptations which lead to increased fitness.
3) Gene products will be probed at the molecular level to understand these adaptations.
Novelty and Timeliness:
The environmental effects of climate change, global urbanisation and its attendant pollution, are often considered on the macrobiological scale, but also drastically impact microbial niches.
Our proposal investigates the underlying principles involved in microbial adaptation to new energy sources in the form of polysaccharides and will provide insights into the flexibility and evolutionary capabilities of the metabolic networks involved. Understanding the global processes that occur will pave the way to exploiting them or designing methods for their alleviation.
HOW TO APPLY
Notes and details of how to apply are available here: https://accedtp.ac.uk/acce-dtp-phd-opportunities-at-university-of-liverpool/
All applicants to ACCE must complete the ACCE personal statement proforma. This is instead of a normal personal/supporting statement/cover letter. The proforma is designed to standardise this part of the application to minimise the difference between those who are given support and those who are not.
The ACCE DTP is committed to recruiting extraordinary future scientists regardless of age, ethnicity, gender, gender identity, disability, sexual orientation or career pathway to date. We understand that commitment and excellence can be shown in many ways and have built our recruitment process to reflect this. We welcome applicants from all backgrounds, particularly those underrepresented in science, who have curiosity, creativity and a drive to learn new skills.
Informal enquiries may be made to Alan.Cartmell@liverpool.ac.uk
Open to students worldwide
NERC ACCE DTP in Ecology and Evolution, programme starts October 2023.
UKRI provide the following funding for 3.5 years:
• Stipend (2022/23 UKRI rate £17,668)
• Tuition Fees at UK fee rate (2022/23 rate £4,596)
• Research support and training grant (RTSG)
Note - UKRI funding only covers UK (Home) fees (£4,596 at 2022/23 rate). A limited number of international fee bursaries will be awarded on a competitive basis. However, if selected International and EU fee rate candidates may need to cover the remaining amount of tuition fees by securing additional funding. International fees for 2022/23 entry were £25,950 (full time) per annum.
2022. Luis AS, Jin C, Byrne DP, Pudlo NA, London JA, Baslé A, Reihill M, Oscarson S, Eyers PA, Czjzek M, Michel G, Barbeyron T, Yates EA, Hansson GC, Karlsson NG, , Martens EC and Cartmell A. Sulfated glycan recognition by carbohydrate sulfatases of the human gut microbiota Corresponding author Nature chem bio
2021. Luis AS, Jin C, Pereira GV, Glowacki RWP, Gugel SR, Singh S, Byrne DP, Pudlo NA, London JA, Baslé A, Reihill M, Oscarson S, Eyers PA, Czjzek M, Michel G, Barbeyron T, Yates EA, Hansson GC, Karlsson NG, Cartmell A, Martens EC. A single sulfatase is required to access colonic mucin by a gut bacterium. Corresponding author Nature
2020. Didier Ndeh, Arnaud Baslé, Henrik Strahl, Edwin A Yates, Urszula L McClurg, Bernard Henrissat, Nicolas Terrapon, Alan Cartmell$ The metabolism of multiple glycosaminoglycans by the human gut symbiont bacteroides thetaiotaomicron is orchestrated by a versatile core genetic locus. Corresponding author Nature commun.
2019. Labourel A, Baslé A, Munoz-Munoz J, Ndeh D, Booth S, Nepogodiev SA, Field RA, Cartmell A$. Structural and functional analyses of glycoside hydrolase 138 enzymes targeting chain A galacturonic acid in the complex pectin rhamnogalacturonan II. Corresponding author J Biol Chem.
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2019 GA McCanney, MA McGrath, TD Otto, R Burchmore, EA Yates, CD Bavington, HJ Willison, JE Turnbull and SC Barnett. Low sulphated heparins target multiple proteins for central nervous system repair. Glia (2019) 67, 668-687.
2018 DP Byrne, Y Li, K Ramakrishhan, IL Barsukov, EA Yates, CE Eyers, D Papy-Garcia, S Chantepie, V Pagadala, J Liu, C Wells, DH Drewry, WJ Zuercher, NG Berry, DG Fernig and PA Eyers. 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, 2417-2433
2017 KL Stewart, E Hughes, EA Yates, DA Middleton and SE Radford. Molecular origins of the compatibility between glycosaminoglycans and Abeta40 amyloid fibrils. J.Mol.Biol., (2017) 429, 2449-2462
2017 MCZ Meneghetti*, TG Ferreira, AK Tashima, SF Chavante, EA Yates, J Liu, HB Nader and MA Lima. Insights into the role of 3-O-sulfotransferase in heparan sulfate biosynthesis. Org. Biomol.Chem., (2017) 15, 6792-6799.