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Nicola Royle

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Nicola Royle
NationalityBritish
Academic background
EducationUniversity of Manchester
Alma materUniversity of Reading
Academic work
DisciplineGenetics
InstitutionsUniversity of Leicester
Main interestsTelomeres

Nicola Jane Royle is a British geneticist who heads the Telomere Research Group in the Department of Genetics and Genome Biology at the University of Leicester.[1] She is a specialist in the cellular processes that affect the stability of telomeres, the essential DNA-protein structures that cap the ends of chromosomes and play significant roles in cancer and ageing.

Early life and education

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Royle earned her B.Sc. degree in Genetics & Cell Biology at the University of Manchester and subsequently her Ph.D.at the University of Reading for her research on the genetics of rare breeds of cattle in Britain.[2]

Career and research

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Following her Ph.D., Royle joined J L Hamerton's human genetics laboratory at the University of Manitoba, Canada as a Postdoctoral Research Fellow.[3][4][5] She then joined Sir Alec Jeffreys’ group at the University of Leicester. During this time she discovered that human GC-rich minisatellites, the markers in genetic fingerprints, are not randomly distributed but clustered towards the ends of human chromosomes.[6] Royle was awarded a six-year MRC-HGMP Senior Research Fellowship to develop an independent research programme in telomere molecular genetics. In 1997 she was appointed Lecturer in Genetics at the University of Leicester and promoted in 2002. She is now an associate professor in the Department of Genetics and Genome Biology.

Royle's research has focused molecular processes that affect the stability of telomeres. She demonstrated that human telomeres evolve along haploid lineages, without frequent recombination in the germline.[7][8][9] She contributed to characterising telomerase-mediated chromosome healing in patients with congenital terminal deletion syndromes.[10] Royle and her group showed that defects in DNA mismatch repair (MMR), particularly loss of MSH2, in colon cancers causes telomere instability[11] and subsequently that some telomere-like repeats, notably (CTAGGG)n, are highly unstable during cell division.[12][13] Her group has made significant contributions to understanding the Alternative Lengthening of Telomeres (ALT) mechanism that is active in some cancers, in particular sarcomas.[14][15]

More recently Royle's group have studied human herpesvirus 6, which can integrate into telomeres and be inherited in families.[16][17] They have shown that the inherited integrated HHV-6 genome (iciHHV-6) can be partially or completely excised, and this can adversely affect telomere length.[18][19] Royle has proposed a model in which excision of the HHV-6 genome occurs through telomere-loop (t-loop) driven processes and may represent the first step towards viral reactivation.[20]

References

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  1. ^ ealb1. "Dr Nicola J. Royle — University of Leicester". www2.le.ac.uk. Retrieved 11 February 2019.{{cite web}}: CS1 maint: numeric names: authors list (link)
  2. ^ Royle, N. J. (1986). "New C-band polymorphism in the White Park cattle of Great Britain". The Journal of Heredity. 77 (5): 366–367. doi:10.1093/oxfordjournals.jhered.a110260. ISSN 0022-1503. PMID 3772068.
  3. ^ Royle, N. J.; Irwin, D. M.; Koschinsky, M. L.; MacGillivray, R. T.; Hamerton, J. L. (1987). "Human genes encoding prothrombin and ceruloplasmin map to 11p11-q12 and 3q21-24, respectively". Somatic Cell and Molecular Genetics. 13 (3): 285–292. doi:10.1007/BF01535211. ISSN 0740-7750. PMID 3474786. S2CID 45686258.
  4. ^ Royle, N. J.; Fung, M. R.; MacGillivray, R. T.; Hamerton, J. L. (1986). "The gene for clotting factor 10 is mapped to 13q32----qter". Cytogenetics and Cell Genetics. 41 (3): 185–188. doi:10.1159/000132225. ISSN 0301-0171. PMID 3754199.
  5. ^ Wood, S.; Poon, R.; Riddell, D. C.; Royle, N. J.; Hamerton, J. L. (1986). "A DNA marker for human chromosome 8 that detects alleles of differing sizes". Cytogenetics and Cell Genetics. 42 (3): 113–118. doi:10.1159/000132262. ISSN 0301-0171. PMID 3460741.
  6. ^ Royle, N. J.; Clarkson, R. E.; Wong, Z.; Jeffreys, A. J. (1988). "Clustering of hypervariable minisatellites in the proterminal regions of human autosomes". Genomics. 3 (4): 352–360. doi:10.1016/0888-7543(88)90127-9. ISSN 0888-7543. PMID 3243550.
  7. ^ Baird, D. M.; Jeffreys, A. J.; Royle, N. J. (1 November 1995). "Mechanisms underlying telomere repeat turnover, revealed by hypervariable variant repeat distribution patterns in the human Xp/Yp telomere". The EMBO Journal. 14 (21): 5433–5443. doi:10.1002/j.1460-2075.1995.tb00227.x. ISSN 0261-4189. PMC 394652. PMID 7489732.
  8. ^ Royle, N. J.; Baird, D. M.; Jeffreys, A. J. (1994). "A subterminal satellite located adjacent to telomeres in chimpanzees is absent from the human genome". Nature Genetics. 6 (1): 52–56. doi:10.1038/ng0194-52. ISSN 1061-4036. PMID 8136835. S2CID 514867.
  9. ^ Royle, N. J.; Hill, M. C.; Jeffreys, A. J. (22 January 1992). "Isolation of telomere junction fragments by anchored polymerase chain reaction". Proceedings. Biological Sciences. 247 (1318): 57–67. doi:10.1098/rspb.1992.0009. ISSN 0962-8452. PMID 1348122. S2CID 19642438.
  10. ^ Varley, H.; Di, S.; Scherer, S. W.; Royle, N. J. (2000). "Characterization of terminal deletions at 7q32 and 22q13.3 healed by De novo telomere addition". American Journal of Human Genetics. 67 (3): 610–622. doi:10.1086/303050. ISSN 0002-9297. PMC 1287521. PMID 10924407.
  11. ^ Pickett, Hilda Amelia; Baird, Duncan Martin; Hoff-Olsen, Per; Meling, Gunn Iren; Rognum, Torleiv Ole; Shaw, Jacqui; West, Kevin Paul; Royle, Nicola Jane (22 April 2004). "Telomere instability detected in sporadic colon cancers, some showing mutations in a mismatch repair gene". Oncogene. 23 (19): 3434–3443. doi:10.1038/sj.onc.1207477. ISSN 0950-9232. PMID 15048084. S2CID 24203652.
  12. ^ Mendez-Bermudez, Aaron; Hills, Mark; Pickett, Hilda A.; Phan, Anh Tuân; Mergny, Jean-Louis; Riou, Jean-François; Royle, Nicola J. (2009). "Human telomeres that contain (CTAGGG)n repeats show replication dependent instability in somatic cells and the male germline". Nucleic Acids Research. 37 (18): 6225–6238. doi:10.1093/nar/gkp629. ISSN 1362-4962. PMC 2764434. PMID 19656953.
  13. ^ Lim, Kah Wai; Alberti, Patrizia; Guédin, Aurore; Lacroix, Laurent; Riou, Jean-François; Royle, Nicola J.; Mergny, Jean-Louis; Phan, Anh Tuân (2009). "Sequence variant (CTAGGG)n in the human telomere favors a G-quadruplex structure containing a G.C.G.C tetrad". Nucleic Acids Research. 37 (18): 6239–6248. doi:10.1093/nar/gkp630. ISSN 1362-4962. PMC 2764449. PMID 19692585.
  14. ^ Varley, Helen; Pickett, Hilda A.; Foxon, Jennifer L.; Reddel, Roger R.; Royle, Nicola J. (2002). "Molecular characterization of inter-telomere and intra-telomere mutations in human ALT cells". Nature Genetics. 30 (3): 301–305. doi:10.1038/ng834. ISSN 1061-4036. PMID 11919561. S2CID 22079632.
  15. ^ Jeyapalan, Jennie N.; Mendez-Bermudez, Aaron; Zaffaroni, Nadia; Dubrova, Yuri E.; Royle, Nicola J. (1 June 2008). "Evidence for alternative lengthening of telomeres in liposarcomas in the absence of ALT-associated PML bodies". International Journal of Cancer. 122 (11): 2414–2421. doi:10.1002/ijc.23412. ISSN 1097-0215. PMID 18311780. S2CID 1309215.
  16. ^ Royle, Nicola J.; Davison, Andrew J.; Jarrett, Ruth F.; Porteous, David J.; Huang, Yan; Cotton, Victoria E.; Neumann, Rita; Armendáriz-Castillo, Isaac; Veal, Colin D. (15 November 2017). "Inherited Chromosomally Integrated Human Herpesvirus 6 Genomes Are Ancient, Intact, and Potentially Able To Reactivate from Telomeres". Journal of Virology. 91 (22): e01137–17. doi:10.1128/JVI.01137-17. ISSN 0022-538X. PMC 5660504. PMID 28835501.
  17. ^ "Inherited herpesvirus study finds links to ancient humans". ScienceDaily. 30 August 2017. Retrieved 20 February 2019.
  18. ^ Royle, Nicola J.; Dyer, Martin J.; Clark, Duncan A.; Wilson, James F.; Winney, Bruce; Jeffreys, Alec J.; Neumann, Rita; Medina-Calzada, Zahara; Wig, Gunjan (1 January 2014). "Human telomeres that carry an integrated copy of human herpesvirus 6 are often short and unstable, facilitating release of the viral genome from the chromosome". Nucleic Acids Research. 42 (1): 315–327. doi:10.1093/nar/gkt840. ISSN 0305-1048. PMC 3874159. PMID 24057213.
  19. ^ Royle, Nicola J.; Dyer, Martin J.; Jayne, Sandrine; Kelpanides, Inga; Majid, Aneela; Siebert, Reiner; Nacheva, Ellie P.; Davison, Andrew J.; Wilkie, Gavin S. (7 March 2016). "HHV-8-unrelated primary effusion-like lymphoma associated with clonal loss of inherited chromosomally-integrated human herpesvirus-6A from the telomere of chromosome 19q". Scientific Reports. 6: 22730. Bibcode:2016NatSR...622730Z. doi:10.1038/srep22730. ISSN 2045-2322. PMC 4779988. PMID 26947392.
  20. ^ Royle, Nicola J.; Wood, Michael L. (2017). "Chromosomally Integrated Human Herpesvirus 6: Models of Viral Genome Release from the Telomere and Impacts on Human Health". Viruses. 9 (7): 184. doi:10.3390/v9070184. PMC 5537676. PMID 28704957.
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