Nicola Stonehouse

Last updated
Nicola Stonehouse

FRSB
Born
Nicola Jane Stonehouse
Alma mater University of East Anglia (BSc)
University of Leeds (PhD)
Scientific career
Fields Molecular virology
InstitutionsUniversity of Leeds
Thesis  (1992)
Website biologicalsciences.leeds.ac.uk/molecular-and-cellular-biology/staff/141/professor-nicola-stonehouse OOjs UI icon edit-ltr-progressive.svg

Nicola Jane Stonehouse FRSB is a British virologist who is a professor in 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.

Contents

Education

Stonehouse studied biology at the University of East Anglia, and graduated in 1983. [2] [3] She moved to the University of Leeds for her graduate studies, where she worked towards a doctorate in medicine, which she completed in 1992. [4]

Research and career

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. [5]

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. [6] [7] 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. [8] 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. [9] As part of the lifecycle of poliovirus it produces empty unstable particles. [10] On their own, these unstable particles would undergo an antigenic conversion to a non-native state. [10] 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. [11] She engineered the virus-like particles using yeast as a recombinant system. [12] [13]

She has explored the viral genomes of various other viruses, including picornaviruses, noroviruses and coronaviruses. [14] Noroviruses are a common cause of gastroenteritis, but there are no vaccines or specific antivirals. [15] [16] Stonehouse has investigated murine norovirus, the form of norovirus that affects mice, using cryogenic electron microscopy. [15] Picornaviridae are a big family of positive-sense RNA viruses, and they contain several human and animal pathogens. [17] 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. [18] This small protein, 3B, is responsible for the efficient replication of foot-and-mouth disease, and demonstrates a significant level of genetic economy. [18] 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. [19]

During the COVID-19 pandemic, Stonehouse provided regular commentary to the public on the status of coronavirus research. [20] From the date of the first UK death coronavirus, Stonehouse emphasised that it was essential that the country improved its diagnostic capacity. [21] She warned the public not to get too optimistic about a COVID-19 vaccine, as they can take "decades" to get to market. [22] 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. [23] [24] She has explained that the National Health Service procurement process makes it difficult to upscale any diagnostic efforts. [25]

Selected publications

Her publications [1] include:

Awards and honours

Stonehouse was elected a Fellow of the Royal Society of Biology (FRSB) in 2014. [29]

Related Research Articles

<span class="mw-page-title-main">Polio</span> Infectious disease caused by poliovirus

Poliomyelitis, commonly shortened to polio, is an infectious disease caused by the poliovirus. Approximately 75% of cases are asymptomatic; mild symptoms which can occur include sore throat and fever; in a proportion of cases more severe symptoms develop such as headache, neck stiffness, and paresthesia. These symptoms usually pass within one or two weeks. A less common symptom is permanent paralysis, and possible death in extreme cases. Years after recovery, post-polio syndrome may occur, with a slow development of muscle weakness similar to that which the person had during the initial infection.

<span class="mw-page-title-main">Norovirus</span> Type of viruses that cause gastroenteritis

Norovirus, sometimes referred to as the winter vomiting disease, is the most common cause of gastroenteritis. Infection is characterized by non-bloody diarrhea, vomiting, and stomach pain. Fever or headaches may also occur. Symptoms usually develop 12 to 48 hours after being exposed, and recovery typically occurs within one to three days. Complications are uncommon, but may include dehydration, especially in the young, the old, and those with other health problems.

<span class="mw-page-title-main">Poliovirus</span> Enterovirus

Poliovirus, the causative agent of polio, is a serotype of the species Enterovirus C, in the family of Picornaviridae. There are three poliovirus serotypes: types 1, 2, and 3.

Viral evolution is a subfield of evolutionary biology and virology that is specifically concerned with the evolution of viruses. Viruses have short generation times, and many—in particular RNA viruses—have relatively high mutation rates. Although most viral mutations confer no benefit and often even prove deleterious to viruses, the rapid rate of viral mutation combined with natural selection allows viruses to quickly adapt to changes in their host environment. In addition, because viruses typically produce many copies in an infected host, mutated genes can be passed on to many offspring quickly. Although the chance of mutations and evolution can change depending on the type of virus, viruses overall have high chances for mutations.

<span class="mw-page-title-main">Picornavirus</span> Family of viruses

Picornaviruses are a group of related nonenveloped RNA viruses which infect vertebrates including fish, mammals, and birds. They are viruses that represent a large family of small, positive-sense, single-stranded RNA viruses with a 30 nm icosahedral capsid. The viruses in this family can cause a range of diseases including the common cold, poliomyelitis, meningitis, hepatitis, and paralysis.

<span class="mw-page-title-main">Mumps virus</span> Viral agent that causes mumps

The mumps virus (MuV) is the virus that causes mumps. MuV contains a single-stranded, negative-sense genome made of ribonucleic acid (RNA). Its genome is about 15,000 nucleotides in length and contains seven genes that encode nine proteins. The genome is encased by a capsid that is in turn surrounded by a viral envelope. MuV particles, called virions, are pleomorphic in shape and vary in size from 100 to 600 nanometers in diameter. One serotype and twelve genotypes that vary in their geographic distribution are recognized. Humans are the only natural host of the mumps virus.

<i>Enterovirus</i> Genus of viruses

Enterovirus is a genus of positive-sense single-stranded RNA viruses associated with several human and mammalian diseases. Enteroviruses are named by their transmission-route through the intestine.

Virus-like particles (VLPs) are molecules that closely resemble viruses, but are non-infectious because they contain no viral genetic material. They can be naturally occurring or synthesized through the individual expression of viral structural proteins, which can then self assemble into the virus-like structure. Combinations of structural capsid proteins from different viruses can be used to create recombinant VLPs. Both in-vivo assembly and in-vitro assembly have been successfully shown to form virus-like particles. VLPs derived from the Hepatitis B virus (HBV) and composed of the small HBV derived surface antigen (HBsAg) were described in 1968 from patient sera. VLPs have been produced from components of a wide variety of virus families including Parvoviridae, Retroviridae, Flaviviridae, Paramyxoviridae and bacteriophages. VLPs can be produced in multiple cell culture systems including bacteria, mammalian cell lines, insect cell lines, yeast and plant cells.

<span class="mw-page-title-main">Sapovirus</span> Genus of viruses

Sapovirus is a genetically diverse genus of single-stranded positive-sense RNA, non-enveloped viruses within the family Caliciviridae. Together with norovirus, sapoviruses are the most common cause of acute gastroenteritis in humans and animals. It is a monotypic taxon containing only one species, the Sapporo virus.

<span class="mw-page-title-main">Bacteriophage MS2</span> Species of virus

Bacteriophage MS2, commonly called MS2, is an icosahedral, positive-sense single-stranded RNA virus that infects the bacterium Escherichia coli and other members of the Enterobacteriaceae. MS2 is a member of a family of closely related bacterial viruses that includes bacteriophage f2, bacteriophage Qβ, R17, and GA.

<span class="mw-page-title-main">Vincent Racaniello</span> American biologist

Vincent R. Racaniello is a Higgins Professor in the Department of Microbiology and Immunology at Columbia University's College of Physicians and Surgeons. He is a co-author of a textbook on virology, Principles of Virology.

<span class="mw-page-title-main">Introduction to viruses</span> Non-technical introduction to viruses

A virus is a tiny infectious agent that reproduces inside the cells of living hosts. When infected, the host cell is forced to rapidly produce thousands of identical copies of the original virus. Unlike most living things, viruses do not have cells that divide; new viruses assemble in the infected host cell. But unlike simpler infectious agents like prions, they contain genes, which allow them to mutate and evolve. Over 4,800 species of viruses have been described in detail out of the millions in the environment. Their origin is unclear: some may have evolved from plasmids—pieces of DNA that can move between cells—while others may have evolved from bacteria.

<span class="mw-page-title-main">Virus</span> Infectious agent that replicates in cells

A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea. Viruses are found in almost every ecosystem on Earth and are the most numerous type of biological entity. Since Dmitri Ivanovsky's 1892 article describing a non-bacterial pathogen infecting tobacco plants and the discovery of the tobacco mosaic virus by Martinus Beijerinck in 1898, more than 11,000 of the millions of virus species have been described in detail. The study of viruses is known as virology, a subspeciality of microbiology.

Mason-Pfizer monkey virus (M-PMV), formerly Simian retrovirus (SRV), is a species of retroviruses that usually infect and cause a fatal immune deficiency in Asian macaques. The ssRNA virus appears sporadically in mammary carcinoma of captive macaques at breeding facilities which expected as the natural host, but the prevalence of this virus in feral macaques remains unknown. M-PMV was transmitted naturally by virus-containing body fluids, via biting, scratching, grooming, and fighting. Cross contaminated instruments or equipment (fomite) can also spread this virus among animals.

<i>Pneumoviridae</i> Family of viruses

Pneumoviridae is a family of negative-strand RNA viruses in the order Mononegavirales. Humans, cattle, and rodents serve as natural hosts. Respiratory tract infections are associated with member viruses such as human respiratory syncytial virus. There are five species in the family which are divided between the genera Metapneumovirus and Orthopneumovirus. The family used to be considered as a sub-family of Paramyxoviridae, but has been reclassified as of 2016.

Triatoma virus (TrV) is a virus belonging to the insect virus family Dicistroviridae. Within this family, there are currently 3 genera and 15 species of virus. Triatoma virus belongs to the genus Cripavirus. It is non-enveloped and its genetic material is positive-sense, single-stranded RNA. The natural hosts of triatoma virus are invertebrates. TrV is a known pathogen to Triatoma infestans, the major vector of Chagas disease in Argentina which makes triatoma virus a major candidate for biological vector control as opposed to chemical insecticides. Triatoma virus was first discovered in 1984 when a survey of pathogens of triatomes was conducted in the hopes of finding potential biological control methods for T. infestans.

Mammalian orthoreovirus (MRV) is a double-stranded RNA virus. It is a part of the family Reoviridae, as well as the subfamily Spinareovirinae. As seen in the name, the Mammalian Ortheoreovirus infects numerous mammalian species and vertebrates which serve as natural hosts. Some diseases that occur as a result of this virus or are associated with this virus include mild upper respiratory illness, and gastrointestinal illness. Examples of these are: upper respiratory tract syndromes, gastroenteritis, biliary atresia, obstructive hydrocephalus, jaundice, alopecia, conjunctivitis, and ‘oily hair’ associated with steatorrhea.

Vaccine shedding is a form of viral shedding which can occur following a viral infection caused by an attenuated vaccine. Illness in others resulting from transmission through this type of viral shedding is rare. Most vaccines are not attenuated vaccines, and therefore cannot cause vaccine-induced viral shedding.

<i>Orthornavirae</i> Kingdom of viruses

Orthornavirae is a kingdom of viruses that have genomes made of ribonucleic acid (RNA), including genes which encode an RNA-dependent RNA polymerase (RdRp). The RdRp is used to transcribe the viral RNA genome into messenger RNA (mRNA) and to replicate the genome. Viruses in this kingdom share a number of characteristics which promote rapid evolution, including high rates of genetic mutation, recombination, and reassortment.

<i>Astroviridae</i> Family of viruses

Astroviridae is a family of non-enveloped ssRNA viruses that cause infections in different animals. The family name is derived from the Greek word astron ("star") referring to the star-like appearance of spikes projecting from the surface of these small unenveloped viruses. Astroviruses were initially identified in humans but have since been isolated from other mammals and birds. This family of viruses consists of two genera, Avastrovirus (AAstV) and Mamastrovirus (MAstV). Astroviruses most frequently cause infection of the gastrointestinal tract but in some animals they may result in encephalitis, hepatitis (avian) and nephritis (avian).

References

  1. 1 2 Nicola Stonehouse publications from Europe PubMed Central
  2. ↑ "Professor Nicola Stonehouse". University of Leeds . Retrieved 19 August 2021.
  3. ↑ "Prof Nicola Stonehouse | The Astbury Centre for Structural Molecular Biology". astbury.leeds.ac.uk. Retrieved 2020-04-27.
  4. ↑ biologicalsciences. "Professor Nicola Stonehouse | School of Molecular and Cellular Biology | University of Leeds". biologicalsciences.leeds.ac.uk. Retrieved 2020-04-27.
  5. ↑ 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.
  6. ↑ Carter [Comms, Martin (3 June 2019). "Research Spotlight - May 2019". leeds.ac.uk. Retrieved 2020-04-26.
  7. ↑ "Scientists prove new approach to Polio vaccines works". ScienceDaily. Retrieved 2020-04-27.
  8. ↑ "New polio vaccine being developed". bbc.com. BBC News. 2010-12-14. Retrieved 2020-04-26.
  9. ↑ Johnson, Kristian (2019-05-16). "Leeds scientists develop groundbreaking new polio vaccine". leedslive. Retrieved 2020-04-26.
  10. 1 2 Society, Microbiology. "An interview with Professor Nicola Stonehouse". microbiologysociety.org. Retrieved 2020-04-26.
  11. ↑ Diamond Light Source. "Lighting up a new path for novel synthetic Polio vaccine - - Diamond Light Source". diamond.ac.uk. Retrieved 2020-04-26.
  12. ↑ biologicalsciences (16 May 2019). "Finding a safer way to make the Polio vaccine". biologicalsciences.leeds.ac.uk. Retrieved 2020-04-26.
  13. ↑ "N8 Lifesavers: University of Leeds developing cheaper and safer vaccines". N8 Research Partnership. 2019-06-25. Retrieved 2020-04-26.
  14. ↑ 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.
  15. 1 2 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.
  16. ↑ "The architecture of a 'shape-shifting' norovirus". ScienceDaily. Retrieved 2020-04-27.
  17. ↑ 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.
  18. 1 2 "Tiny protein offers major insight into foot-and-mouth virus". ScienceDaily. Retrieved 2020-04-27.
  19. ↑ "£5m project to help combat the foot-and-mouth threat". yorkshirepost.co.uk. 26 November 2012. Retrieved 2020-04-27.
  20. ↑ Kobie, Nicole (2020-03-27). "Where is the world at with a coronavirus vaccine?". Wired UK. ISSN   1357-0978 . Retrieved 2020-04-26.
  21. ↑ "expert reaction to first death in the UK of patient who tested positive for COVID-19 | Science Media Centre" . Retrieved 2020-04-26.
  22. ↑ 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.
  23. ↑ Sample, Ian; Mason, Rowena (2020-04-01). "Just 2,000 key NHS staff have been tested, UK government admits". The Guardian . ISSN   0261-3077 . Retrieved 2020-04-26.
  24. ↑ 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.{{cite news}}: |last= has generic name (help)
  25. ↑ 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.
  26. ↑ 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.
  27. ↑ 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.
  28. ↑ 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. PMC   7612263 . PMID   17434527.
  29. ↑ "Roll of Honour List" (PDF). Retrieved 2020-04-26.
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