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  White Rose BBSRC DTP i-CASE studentship with AstraZeneca: New technologies for the characterization of mRNA therapeutics/vaccines


   White Rose BBSRC Doctoral Training Partnership

  Prof Mark Dickman, Dr Piera Marchetti, Dr Tatyana Shelkovnikova, Prof J Sayers  Sunday, January 07, 2024  Funded PhD Project (Students Worldwide)

About the Project

mRNA technology has recently demonstrated the ability to significantly change the timeline for developing and delivering a new vaccine from years to months, highlighted by the successful development and approval of two mRNA vaccines for COVID-19.

The development of new tools/technologies for the analysis of mRNA therapeutics is critical to underpin manufacturing and the development of new mRNA therapeutics/vaccines.

Direct RNA sequence mapping is a powerfull new method utilised for the characterisation of mRNA therapetucs. However, there are limited RNase enzymes that can be used, limiting the application of such methods for the characterization of mRNA. It is proposed to develop a toolbox of RNA restriction enzymes based on the MazF endonucleases from different organisms that exhibit different sequence specificities.

Training will be provided in a wide range of state of the art equipment including HPLC/UHPLC, mass spectrometry, capillary electrophoresis, protein expression and purification.

  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) Chemistry (6) 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

Vanhinsbergh CJ, Criscuolo A, Sutton JN, Murphy K, Williamson AJK, Cook K, Dickman MJ. Characterization and Sequence Mapping of Large RNA and mRNA Therapeutics Using Mass Spectrometry. Anal Chem. 2022 ;94 (20): 7339-7349
Nwokeoji AO, Earll ME, Kilby PM, Portwood DE, Dickman MJ. (2019) High resolution fingerprinting of single and double-stranded RNA using ion-pair reverse-phase chromatography. J Chromatogr B Analyt Technol Biomed Life Sci. 1104:212-219
1.
Nwokeoji AO, Kumar S, Kilby PM, Portwood DE, Hobbs JK, Dickman MJ (2019) Analysis of long dsRNA produced in vitro and in vivo using atomic force microscopy in conjunction with ion-pair reverse-phase HPLC. Analyst. 5;144(16):4985-4994
Howard JD, Beghyn M, Dewulf N, De Vos Y, Philips A, Portwood D, Kilby PM, Oliver D, Maddelein W, Brown S, Dickman MJ. Chemically modified dsRNA induces RNAi effects in insects in vitro and in vivo: A potential new tool for improving RNA-based plant protection. J Biol Chem. 2022, 298(9):102311
Shona M. Richardson, Piera M. Marchetti, Michael A. Herrera, and Dominic J. Campopiano, ACS Catal. 2022, 12, 12701-12710.
Piera M. Marchetti, Shona M. Richardson, Noor M. Kariem and Dominic J. Campopiano, Med. Chem. Comm. 2019, 10, 1192-1196.
Piera M. Marchetti, Van Kelly, Joanna P. Simpson, Mairi Ward and Dominic J. Campopiano, Org. Biomol. Chem. 2018, 16, 2735-2740
1. An H, Elvers KT, Gillespie JA, Jones K, Atack JR, Grubisha O, Shelkovnikova TA* (2022) A toolkit for the identification of NEAT1_2/paraspeckle modulators. Nucleic Acids Research, gkac771.
2. An H, Litscher G, Watanabe N, Wei W, Hashimoto T, Iwatsubo T, Buchman VL, Shelkovnikova TA* (2021) ALS-linked cytoplasmic FUS assemblies are compositionally different from physiological stress granules and sequester hnRNPA3, a novel modifier of FUS toxicity. Neurobiol Dis. 162(105585).
3. An H, Tan J.-T., Shelkovnikova TA* (2019) Stress granules regulate stress-induced paraspeckle assembly. J Cell Biol. 218(12):4127-414.
4. Shelkovnikova TA*, An H, Skelt L, Tregoning JS, Humphreys IR, Buchman VL (2019) Antiviral Immune Response as a Trigger of FUS Proteinopathy in Amyotrophic Lateral Sclerosis. Cell Rep. 29(13):4496-4508.e4.
Postgraduate co-author in bold. *corresponding author