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  White Rose BBSRC DTP i-CASE studentship with Oxford Nanopore Technologies (ONT): Exploring Structures of Membrane-Inserted Helicases for Advancing Nanopore Sequencing Revolution


   White Rose BBSRC Doctoral Training Partnership

  Prof Fred Antson, Dr Mark Bruce, Dr Oliver Bayfield  Sunday, January 07, 2024  Funded PhD Project (Students Worldwide)

About the Project

Join the Nanopore Sequencing Revolution

Ready to dive into ground-breaking DNA sequencing research? Recent advances in DNA sequencing are revolutionizing fields like medicine, healthcare, food supply chains, and environmental safety. At the heart of this revolution is nanopore sequencing, a cutting-edge technique using 1nm pores in a membrane to detect electrical signals as DNA bases pass through.

But here's the exciting part: We're pushing the boundaries of nanopore sequencing by harnessing bioinspired protein nanopores. These ultra-sensitive structures can enhance reliability and prolong pore lifespan. Oxford Nanopore Technologies (ONT) already achieves 99% sequencing accuracy, but we aim to merge the membrane pore and helicase into a single protein for a sequencing revolution.

How? We're pioneering direct membrane insertion of hexameric helicases to improve translocation speed and pore stability.

Why Choose this Project: Your Path to Innovation

This is an invitation to join an interdisciplinary collaboration spanning molecular biology, protein biochemistry, structural biology, and single-molecule biophysics. You'll straddle academia at the University of York and industrial biotechnology R&D at ONT. Plus, we're partnering with Dr. Sanders' lab at the University of Sheffield for helicase characterization.

Financial Support for Your Ambitions

This fully funded opportunity includes a BBSRC stipend, ONT supplement, and funding for your ONT placement. Picture yourself in a dynamic research environment with renowned academics and entrepreneurs. Under ONT's guidance, you'll explore industrial potential and cross-disciplinary collaboration.

Your Launchpad for the Future

At the University of York, you'll participate in world-class academic research, setting your foundation for a future in academia, industry, or start-ups.

Ready for a scientific revolution in DNA sequencing? Join us on this journey where your passion meets the potential of nanopore sequencing. Apply now to shape the future!

  About the DTP

This studentship is offered as part of the White Rose BBSRC Doctoral Training Partnership (DTP) in Mechanistic Biology, which brings together the research of the world-class molecular and cellular bioscience centres at the White Rose universities of Leeds, Sheffield and York.

Our mission is to train excellent bio-scientists who understand how living systems work and can innovate to address global challenges, such as the impact of climate change, a healthier old age, sustainable food production, land use and energy production.

What is on offer?

This is an i-CASE (industry partnership) studentship for entry in October 2024.  

Join us and you will receive a 4-year, funded PhD programme of research and skills training, with cross-disciplinary supervision, plus a structured programme of cohort-wide training and networking events. A highlight is the annual symposium, which is planned and delivered by students.

A unique part of your training will be a fully-funded placement of at least 3 months with the industry partner.

How to apply – Expression of Interest

Students may apply for up to three projects anywhere in the Doctoral Training Partnership (DTP).  Applications will be to the DTP centrally, using an online Expression of Interest (EoI). The EoI will include:

§ CV information; not submitted separately

§ Equality, Diversity and Inclusion (EDI) data

§ Names of two referees

Deadline for EoIs is midnight Sunday 7th January 2024.

Submit EoIs using this link: https://leeds.onlinesurveys.ac.uk/white-rose-bbsrc-dtp-expression-of-interest-form

Shortlisted candidates will be required to make formal applications to the Graduate School at each institution, supplying the necessary paperwork.

Details of the interview process will be decided by the academic and industry partners for this project

Website: https://www.whiterose-mechanisticbiology-dtp.ac.uk/

 

Biological Sciences (4) Mathematics (25)

Funding Notes

Appointed candidates will be fully funded for 4 years:
 Tax-free annual stipend at the UKRI rate. The rate for starters in 2023/24 was £18,622. (Rates for 2024/25 starters are not yet available).
 UKRI tuition fees – These are paid directly to the host institution.
 A Research Training and Support Grant
 An allowance for Fieldwork/Conference/Travel
 A fully funded placement with the industry partner
 The industry partner may also make an additional contribution to the research costs and, in some cases, they may offer an uplift to the stipend.

References

Hawkins DEDP, Bayfield OW, Fung HKH, Grba DN Huet A, Conway JF, Antson AA: Insights into a viral motor: the structure of the HK97 packaging termination assembly. Nucleic Acids Research, 2023, 51: 7025-7035
Mojtabavi M, Greive SJ, Antson AA, Wanunu M. High-Voltage Biomolecular Sensing Using a Bacteriophage Portal Protein Covalently Immobilized within a Solid-State Nanopore. J Am Chem Soc. 2022, 144:22540-22548.
Bayfield OW, Shkoporov AN, Yutin N, Khokhlova EV, Smith JLR, Hawkins DEDP, Koonin EV, Hill C, Antson AA: Structural atlas of a human gut crassvirus. Nature, 2023, 617, 409–416.
Fung HKH, Grimes S, Huet A, Duda RL, Chechik M, Gault J, Robinson CV, Hendrix RW, Jardine PJ, Conway JF, Baumann CG, Antson AA: Structural basis of DNA packaging by a ring-type ATPase from an archetypal viral system. Nucleic Acids Research, 2022, 50, 8719-8732.
ONT’s primary activity is commercial research and thus company research scientists do not typically publish papers.
Collaborations with academic groups have realised the following published studies:
1. Highly parallel direct RNA sequencing on an array of nanopores, Daniel R Garalde, Elizabeth A Snell, Daniel Jachimowicz, Andrew J Heron, Mark Bruce, Joseph Lloyd, Anthony Warland, Nadia Pantic, Tigist Admassu, Jonah Ciccone, Sabrina Serra, Jemma Keenan, Samuel Martin, Luke McNeill, Jayne Wallace, Lakmal Jayasinghe, Chris Wright, Javier Blasco, Botond Sipos, Stephen Young, Sissel Juul, James Clarke, Daniel J Turner (2018). “Highly parallel direct RNA sequencing on an array of nanopores” Nature Methods 15, 201–206.
2. Marjetka Podobnik , Peter Savory, Nejc Rojko , Matic Kisovec, Neil Wood, Richard Hambley, Jonathan Pugh, E. Jayne Wallace, Luke McNeill, Mark Bruce, Idlir Liko, Timothy M. Allison, Shahid Mehmood, Neval Yilmaz, Toshihide Kobayashi, Robert J.C. Gilbert, Carol V. Robinson, Lakmal Jayasinghe & Gregor Anderluh. (2016) Crystal structure of an invertebrate cytolysin pore reveals unique properties and mechanism of assembly Nature Comms 7, 11598
Inventor on several patents including WO2014013260A1- modified helicases
Bayfield OW, Shkoporov AN, Yutin N, Khokhlova EV, Smith JLR, Hawkins DEDP, Koonin EV, Hill C, Antson AA: Structural atlas of a human gut crassvirus. Nature, 2023, 617, 409–416.
Dong T et al (66 authors including 4 authors from York: Hawkins EDP, Ker DS, Bayfield OW and Antson AA) ‘Broad and strong memory CD4 + and CD8 + T cells induced by SARS-CoV-2 in UK convalescent COVID-19 patients’. Nature Immunology. 2020. DOI: 10.1038/s41590-020-0782-6.
Bayfield OW, Steven AC, Antson AA: Cryo-EM structure in situ reveals a molecular switch that safeguards virus against genome loss. eLife 2020; 9: e55517, DOI: 10.7554/eLife.55517.
Bayfield OW, Klimuk E, Winkler DC, Hesketh EL, Chechik M, Cheng N, Dykeman EC, Minakhin L, Ranson NA, Severinov K, Steven AC, Antson AA*: Cryo-EM structure and in vitro DNA packaging of a thermophilic virus with supersized T=7 capsids. PNAS, 2019, 116:3556-3561.