Nicola Stonehouse

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Nicola Stonehouse

Born
Nicola Jane Stonehouse
Alma materUniversity of East Anglia (BSc)
University of Leeds (PhD)
Scientific career
FieldsMolecular virology
InstitutionsUniversity of Leeds
Thesis (1992)
Websitebiologicalsciences.leeds.ac.uk/molecular-and-cellular-biology/staff/141/professor-nicola-stonehouse Edit this at Wikidata

Nicola Jane Stonehouse FRSB is a British virologist who is a Professor of molecular virology at the University of Leeds.[1] Her research investigates viral diseases and the use of RNA aptamers to study viral proteins. She has worked on the development of a novel poliovirus vaccine that makes use of virus-like particles.

Education[edit]

Stonehouse studied biology at the University of East Anglia, and graduated in 1983.[2] She moved to the University of Leeds for her graduate studies, where she worked towards a doctorate in medicine, which she completed in 1992.[3]

Research and career[edit]

After her PhD, Stonehouse was awarded a Medical Research Council (MRC) clinical fellowship, where she was the first to describe the crystal structure of an RNA aptamer–protein complex.[4]

Her research investigates the factors that can inhibit replication, with a focus on viral polymerases. She has developed several virus-like particles that may be able to act as vaccinations for emerging diseases. These virus-like particles (capsids) cannot cause disease themselves, but can be used to elicit an immune response. Amongst these studies, Stonehouse used this technology to work toward a safer polio vaccine.[5][6] Her research was supported by the Bill & Melinda Gates Foundation, and made use of the virus-like particle strategy to trick the body into developing immunity against poliovirus. Stonehouse used an empty protein shell, designed to look and behave like poliovirus, which could trigger the immune system.[7] A synthetic vaccine can be safer than a traditional vaccine as there is no risk of accidentally releasing the virus, and does not require a biocontainment laboratory.[8] As part of the lifecycle of poliovirus it produces empty unstable particles.[9] On their own, these unstable particles would undergo an antigenic conversion to a non-native state.[9] To precisely mimic the shell of the poliovirus, Stonehouse and co-workers studied the structure at the Diamond Light Source. Using a combination of electron microscopy and crystal structures, the team identified ways to stabilise this virus-like particle shell.[10] She engineered the virus-like particles using yeast as a recombinant system.[11][12]

She has explored the viral genomes of various other viruses, including picornaviruses, noroviruses and coronaviruses.[13] Noroviruses are a common cause of gastroenteritis, but there are no vaccines or specific antivirals.[14][15] Stonehouse has investigated murine norovirus, the form of norovirus that affects mice, using cryogenic electron microscopy.[14] Picornaviridae are a big family of positive-sense RNA viruses, and they contain several human and animal pathogens.[16] In her investigations of foot-and-mouth disease, a sometimes fatal viral infection which is caused by a picornavirus, Stonehouse identified a small protein which is important in the viral replication.[17] This small protein, 3B, is responsible for the efficient replication of foot-and-mouth disease, and demonstrates a significant level of genetic economy.[17] In 2012 Stonehouse was award a research grant from the Biotechnology and Biological Sciences Research Council (BBSRC) to develop new generation vaccines to protect cattle, sheep, goats and pigs.[18]

During the COVID-19 pandemic, Stonehouse provided regular commentary to the public on the status of coronavirus research.[19] From the date of the first UK death coronavirus, Stonehouse emphasised that it was essential that the country improved its diagnostic capacity.[20] She warned the public not to get too optimistic about a COVID-19 vaccine, as they can take "decades" to get to market.[21] Stonehouse called for the Government of the United Kingdom to make it easier for universities and industrial labs to support testing efforts. She believes that an over-reliance on specific reagents made it difficult for testing centres to run at capacity.[22][23] She has explained that the National Health Service procurement process makes it difficult to upscale any diagnostic efforts.[24]

Selected publications[edit]

Her publications[1] include:

  • Crystal structure of an RNA bacteriophage coat protein–operator complex[25]
  • The three-dimensional structures of two complexes between recombinant MS2 capsids and RNA operator fragments reveal sequence-specific protein-RNA interactions[26]
  • A Simple, RNA-Mediated Allosteric Switch Controls the Pathway to Formation of a T=3 Viral Capsid[27]

Awards and honours[edit]

Stonehouse was elected a Fellow of the Royal Society of Biology (FRSB) in 2014.[28]

References[edit]

  1. ^ a b Nicola Stonehouse publications from Europe PubMed Central
  2. ^ "Prof Nicola Stonehouse | The Astbury Centre for Structural Molecular Biology". astbury.leeds.ac.uk. Retrieved 2020-04-27.
  3. ^ biologicalsciences. "Professor Nicola Stonehouse | School of Molecular and Cellular Biology | University of Leeds". biologicalsciences.leeds.ac.uk. Retrieved 2020-04-27.
  4. ^ Convery, Maire A.; Rowsell, Siân; Storehouse, Nicola J.; Ellington, Andrew D.; Hirao, Ichira; Murray, James B.; Peabody, David S.; Phillips, Simon E. V.; Stockley, Peter G. (1998). "Crystal structure of an RNA aptamer–protein complex at 2.8 Å resolution". Nature Structural Biology. 5 (2): 133–139. doi:10.1038/nsb0298-133. ISSN 1545-9985. PMID 9461079. S2CID 25128504.
  5. ^ Carter [Comms, Martin. "Research Spotlight - May 2019". leeds.ac.uk. Retrieved 2020-04-26.
  6. ^ "Scientists prove new approach to Polio vaccines works". ScienceDaily. Retrieved 2020-04-27.
  7. ^ "New polio vaccine being developed". bbc.com. BBC News. 2010-12-14. Retrieved 2020-04-26.
  8. ^ Johnson, Kristian (2019-05-16). "Leeds scientists develop groundbreaking new polio vaccine". leedslive. Retrieved 2020-04-26.
  9. ^ a b Society, Microbiology. "An interview with Professor Nicola Stonehouse". microbiologysociety.org. Retrieved 2020-04-26.
  10. ^ Diamond Light Source. "Lighting up a new path for novel synthetic Polio vaccine - - Diamond Light Source". diamond.ac.uk. Retrieved 2020-04-26.
  11. ^ biologicalsciences. "Finding a safer way to make the Polio vaccine". biologicalsciences.leeds.ac.uk. Retrieved 2020-04-26.
  12. ^ Partnership, N8 Research (2019-06-25). "N8 Lifesavers: University of Leeds developing cheaper and safer vaccines". N8 Research Partnership. Retrieved 2020-04-26.
  13. ^ Herod, Morgan R.; Gold, Sarah; Lasecka-Dykes, Lidia; Wright, Caroline; Ward, Joseph C.; McLean, Thomas C.; Forrest, Sophie; Jackson, Terry; Tuthill, Tobias J.; Rowlands, David J.; Stonehouse, Nicola J. (2017). Semler, Bert L. (ed.). "Genetic economy in picornaviruses: Foot-and-mouth disease virus replication exploits alternative precursor cleavage pathways". PLOS Pathogens. 13 (10): e1006666. doi:10.1371/journal.ppat.1006666. ISSN 1553-7374. PMC 5638621. PMID 28968463.
  14. ^ a b Snowden, Joseph S.; Hurdiss, Daniel L.; Adeyemi, Oluwapelumi O.; Ranson, Neil A.; Herod, Morgan R.; Stonehouse, Nicola J. (2020). "Dynamics in the murine norovirus capsid revealed by high-resolution cryo-EM". PLOS Biology. 18 (3): e3000649. doi:10.1371/journal.pbio.3000649. ISSN 1545-7885. PMC 7108717. PMID 32231352.
  15. ^ "The architecture of a 'shape-shifting' norovirus". ScienceDaily. Retrieved 2020-04-27.
  16. ^ Herod, Morgan R.; Ferrer-Orta, Cristina; Loundras, Eleni-Anna; Ward, Joseph C.; Verdaguer, Nuria; Rowlands, David J.; Stonehouse, Nicola J. (2016). "Both cis and trans Activities of Foot-and-Mouth Disease Virus 3D Polymerase Are Essential for Viral RNA Replication". Journal of Virology. 90 (15): 6864–6883. doi:10.1128/JVI.00469-16. ISSN 0022-538X. PMC 4944275. PMID 27194768.
  17. ^ a b "Tiny protein offers major insight into foot-and-mouth virus". ScienceDaily. Retrieved 2020-04-27.
  18. ^ "£5m project to help combat the foot-and-mouth threat". yorkshirepost.co.uk. Retrieved 2020-04-27.
  19. ^ Kobie, Nicole (2020-03-27). "Where is the world at with a coronavirus vaccine?". Wired UK. ISSN 1357-0978. Retrieved 2020-04-26.
  20. ^ "expert reaction to first death in the UK of patient who tested positive for COVID-19 | Science Media Centre". Retrieved 2020-04-26.
  21. ^ Lee, Alex (2020-02-06). "Why we shouldn't pin our hopes on a coronavirus vaccine". Wired UK. ISSN 1357-0978. Retrieved 2020-04-26.
  22. ^ Sample, Ian; Mason, Rowena (2020-04-01). "Just 2,000 key NHS staff have been tested, UK government admits". theguardian.com. The Guardian. ISSN 0261-3077. Retrieved 2020-04-26.
  23. ^ editor, Rowena Mason Deputy political (2020-04-02). "Boris Johnson restates pledge to boost UK coronavirus testing capacity". The Guardian. ISSN 0261-3077. Retrieved 2020-04-26.CS1 maint: extra text: authors list (link)
  24. ^ Chawla2020-04-15T13:30:00+01:00, Dalmeet Singh. "UK seeks to scale-up Covid-19 testing but large gaps in capabilities remain". Chemistry World. Retrieved 2020-04-27.
  25. ^ Valegård, Karin; Murray, James B.; Stockley, Peter G.; Stonehouse, Nicola J.; Liljas, Lars (1994). "Crystal structure of an RNA bacteriophage coat protein–operator complex". Nature. 371 (6498): 623–626. Bibcode:1994Natur.371..623V. doi:10.1038/371623a0. ISSN 1476-4687. PMID 7523953. S2CID 4322214.
  26. ^ Valegård, Karin; Murray, James B; Stonehouse, Nicola J; van den Worm, Sjoerd; Stockley, Peter G; Liljas, Lars (1997). "The three-dimensional structures of two complexes between recombinant MS2 capsids and RNA operator fragments reveal sequence-specific protein-RNA interactions". Journal of Molecular Biology. 270 (5): 724–738. doi:10.1006/jmbi.1997.1144. ISSN 0022-2836. PMID 9245600.
  27. ^ Stockley, Peter G.; Rolfsson, Ottar; Thompson, Gary S.; Basnak, Gabriella; Francese, Simona; Stonehouse, Nicola J.; Homans, Steven W.; Ashcroft, Alison E. (2007-06-01). "A Simple, RNA-Mediated Allosteric Switch Controls the Pathway to Formation of a T=3 Viral Capsid". Journal of Molecular Biology. 369 (2): 541–552. doi:10.1016/j.jmb.2007.03.020. ISSN 0022-2836. PMID 17434527.
  28. ^ "Roll of Honour List" (PDF). Retrieved 2020-04-26.