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Robin Allshire

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Robin Allshire
Robin Allshire in 2019
Born
Robin Campbell Allshire

1960 (age 63–64)
EducationTrinity College Dublin (BSc)
University of Edinburgh (PhD)
Scientific career
FieldsEpigenetics
Heterochromatin
Chromatin
Centromere
Kinetochore[1]
InstitutionsUniversity of Edinburgh
Cold Spring Harbor Laboratory
ThesisConstruction and analysis of vectors based on bovine papilloma virus (1985)
Doctoral advisorChris Bostock
Edwin Southern[2]
Other academic advisorsNicholas Hastie
Websiteallshirelab.com

Robin Campbell Allshire (born 19 May 1960) is a British academic who is Professor of Chromosome Biology[3] at University of Edinburgh and a Wellcome Trust Principal Research Fellow.[4][1] His research group at the Wellcome Trust Centre for Cell Biology[5] focuses on the epigenetic mechanisms governing the assembly of specialised domains of chromatin and their transmission through cell division.[6]

Early life and education

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Allshire grew up in the fishing village of Howth, Co Dublin 1960–1978.[citation needed] His parents were Arthur Gordon Allshire (1925-2012) who was a Pharmacist and Freda Margaret (née Schmutz; 1933–2014).[7][8] He was awarded his Bachelor of Arts degree in Genetics by Trinity College Dublin, in 1981[citation needed] where he was motivated by the inspirational teaching of David McConnell and colleagues at the Dept of Genetics to undertake post-graduate studies.[9] He subsequently joined the Medical Research Council (MRC) Mammalian Genome Unit at the University of Edinburgh where he obtained his PhD in 1985[2] under the guidance of Chris Bostock and Edwin Southern investigating the use of bovine papillomavirus as a chassis for mammalian artificial chromosome construction.[2]

Career and research

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In 1985 Allshire joined Nicholas Hastie's research group at the MRC Human Genetics Unit, Edinburgh (formerly MRC Clinical and Population Cytogentics Unit) as a postdoctoral researcher where he discovered that mammalian telomeres are composed of simple repetitive sequences similar to those of unicellular eukaryotes[10] and that telomere length in blood cells shorten with age and are further eroded in cancerous cells.[11] This work resulted from following the fate of fission yeast (Schizosaccharomyces pombe) telomeres after introdroducing fission yeast chromosomes into mouse cell in collaboration with Peter Fantes.[12] In 1989 he took a position as an independent visiting scientist at Cold Spring Harbor Laboratory (CSHL) for 18 months before joining the MRC Human Genetics Unit as a junior group leader. While at CSHL he decided to switch his focus to investigating chromosomal elements in the genetically tractable fission yeast.[13] At the MRC HGU, Edinburgh (1990 - 2002), and subsequently at the Wellome Trust Centre for Cell Biology, University of Edinburgh (2002–present), he discovered that genes are silenced when placed within fission yeast centromeres[14][15] and telomeres,[16] and then utilised this gene silencing to gain fundamental insights into the processes of chromosome segregation,[17][18][19] and heterochromatin[20][21][22][23] and kinetochore CENP-A chromatin[24][25][26][27][28][29] establishment[30][31] and maintenance.[32][33][34] He is particularly interested in the epigenetic mechanisms that allow the persistence of specialised chromatin domains through multiple cell divisions and meiosis.[35] He has investigated how RNA interference (RNAi) mediates heterochromatin formation[36][37][38] and shown that splicing factors contribute to heterochromatin integrity via siRNA generation and RNAi.[39][40] He has provided insight into how transcription and resulting non-coding RNA might influence the assembly of specialised CENP-A chromatin[41][42][43][44] and demonstrated that some acts of lncRNA transcription are responsive to environmental stimuli and regulate neighbouring genes by transcriptional interference.[45][46] Recently using fission yeast his team discovered an epigenetic mechanism that allows fungi to develop resistance to antifungal drugs without alterations to their DNA.[47] This finding is important for understanding how pathogenic fungi become resistant to the limited number of available antifungal agents in both clinical and agricultural arenas.

Awards and honours

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Allshire was elected a Fellow of the Royal Society of Edinburgh in 2005,[48] a Fellow of the Royal Society (FRS) in 2011 [49] and a Fellow of the Academy of Medical Sciences (FMedSci) in 2020.[50]

References

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  1. ^ a b Robin Allshire publications indexed by Google Scholar Edit this at Wikidata
  2. ^ a b c Allshire, Robin Campbell (1985). Construction and analysis of vectors based on bovine papilloma virus (PhD thesis). University of Edinburgh. hdl:1842/11176. OCLC 606010479. EThOS uk.bl.ethos.355979. Free access icon
  3. ^ "Allshire lab members".
  4. ^ "Principal Research Fellowships: people we've funded". wellcome.ac.uk. Wellcome Trust.
  5. ^ "Wellcome Centre for Cell Biology - Wellcome Centre for Cell Biology". University of Edinburgh.
  6. ^ "Wellcome Trust lab". 11 January 2024.
  7. ^ "ALLSHIRE, Arthur : Death notice - Irish Times Family Notices". The Irish Times.
  8. ^ "ALLSHIRE, Freda Margaret : Death notice - Irish Times Family Notices". The Irish Times.
  9. ^ "EPIGENETICS AND SPECIALIZED CHROMATIN".
  10. ^ Allshire, Robin C; Gosden, John R; Cross, Sally H; Cranston, Gwen; Rout, Derek; Sugawara, Neal; Szostak, Jack W; Fantes, Peter A; Hastie, Nicholas D (1988). "Telomeric repeat from T. Thermophila cross hybridizes with human telomeres". Nature. 332 (6165): 656–9. Bibcode:1988Natur.332..656A. doi:10.1038/332656a0. PMID 2833706. S2CID 4352376.
  11. ^ Hastie, Nicholas D; Dempster, Maureen; Dunlop, Malcolm G; Thompson, Alastair M; Green, Daryll K; Allshire, Robin C (1990). "Telomere reduction in human colorectal carcinoma and with ageing". Nature. 346 (6287): 866–8. Bibcode:1990Natur.346..866H. doi:10.1038/346866a0. PMID 2392154. S2CID 4258451.
  12. ^ Allshire, R. C; Cranston, G; Gosden, J. R; Maule, J. C; Hastie, N. D; Fantes, P. A (1987). "A fission yeast chromosome can replicate autonomously in mouse cells". Cell. 50 (3): 391–403. doi:10.1016/0092-8674(87)90493-4. PMID 3475186. S2CID 2193386.
  13. ^ Allshire, R. C (1990). "Introduction of large linear minichromosomes into Schizosaccharomyces pombe by an improved transformation procedure". Proceedings of the National Academy of Sciences of the United States of America. 87 (11): 4043–7. Bibcode:1990PNAS...87.4043A. doi:10.1073/pnas.87.11.4043. PMC 54043. PMID 2349217.
  14. ^ Allshire, R. C; Javerzat, J. P; Redhead, N. J; Cranston, G (1994). "Position effect variegation at fission yeast centromeres". Cell. 76 (1): 157–69. doi:10.1016/0092-8674(94)90180-5. PMID 8287474. S2CID 42369473.
  15. ^ Allshire, R. C; Nimmo, E. R; Ekwall, K; Javerzat, J. P; Cranston, G (1995). "Mutations derepressing silent centromeric domains in fission yeast disrupt chromosome segregation". Genes & Development. 9 (2): 218–33. doi:10.1101/gad.9.2.218. PMID 7851795.
  16. ^ Nimmo, E. R; Cranston, G; Allshire, R. C (1994). "Telomere-associated chromosome breakage in fission yeast results in variegated expression of adjacent genes". The EMBO Journal. 13 (16): 3801–11. doi:10.1002/j.1460-2075.1994.tb06691.x. PMC 395293. PMID 8070408.
  17. ^ Nimmo, Elaine R; Pidoux, Alison L; Perry, Paul E; Allshire, Robin C (1998). "Defective meiosis in telomere-silencing mutants of Schizosaccharomyces pombe". Nature. 392 (6678): 825–8. Bibcode:1998Natur.392..825N. doi:10.1038/33941. PMID 9572142. S2CID 4412433.
  18. ^ Pidoux, A. L; Uzawa, S; Perry, P. E; Cande, W. Z; Allshire, R. C (2000). "Live analysis of lagging chromosomes during anaphase and their effect on spindle elongation rate in fission yeast". Journal of Cell Science. 113 Pt 23 (23): 4177–91. doi:10.1242/jcs.113.23.4177. PMID 11069763.
  19. ^ Bernard, P; Maure, J. F; Partridge, J. F; Genier, S; Javerzat, J. P; Allshire, R. C (2001). "Requirement of Heterochromatin for Cohesion at Centromeres". Science. 294 (5551): 2539–42. Bibcode:2001Sci...294.2539B. doi:10.1126/science.1064027. PMID 11598266. S2CID 31166180.
  20. ^ Ekwall, K; Javerzat, J. P; Lorentz, A; Schmidt, H; Cranston, G; Allshire, R (1995). "The chromodomain protein Swi6: A key component at fission yeast centromeres". Science. 269 (5229): 1429–31. Bibcode:1995Sci...269.1429E. doi:10.1126/science.7660126. PMID 7660126. S2CID 38678389.
  21. ^ Ekwall, K; Olsson, T; Turner, B. M; Cranston, G; Allshire, R. C (1997). "Transient inhibition of histone deacetylation alters the structural and functional imprint at fission yeast centromeres". Cell. 91 (7): 1021–32. doi:10.1016/S0092-8674(00)80492-4. PMID 9428524.
  22. ^ Bannister, Andrew J; Zegerman, Philip; Partridge, Janet F; Miska, Eric A; Thomas, Jean O; Allshire, Robin C; Kouzarides, Tony (2001). "Selective recognition of methylated lysine 9 on histone H3 by the HP1 chromo domain". Nature. 410 (6824): 120–4. Bibcode:2001Natur.410..120B. doi:10.1038/35065138. PMID 11242054. S2CID 4334447.
  23. ^ Partridge, J. F; Scott, K. S; Bannister, A. J; Kouzarides, T; Allshire, R. C (2002). "Cis-acting DNA from fission yeast centromeres mediates histone H3 methylation and recruitment of silencing factors and cohesin to an ectopic site". Current Biology. 12 (19): 1652–60. doi:10.1016/S0960-9822(02)01177-6. PMID 12361567.
  24. ^ Pidoux, Alison L; Richardson, William; Allshire, Robin C (2003). "Sim4". The Journal of Cell Biology. 161 (2): 295–307. doi:10.1083/jcb.200212110. PMC 2172903. PMID 12719471.
  25. ^ Castillo, A. G; Mellone, B. G; Partridge, J. F; Richardson, W; Hamilton, G. L; Allshire, R. C; Pidoux, A. L (2007). "Plasticity of fission yeast CENP-A chromatin driven by relative levels of histone H3 and H4". PLOS Genetics. 3 (7): e121. doi:10.1371/journal.pgen.0030121. PMC 1934396. PMID 17677001.
  26. ^ Dunleavy, Elaine M; Pidoux, Alison L; Monet, Marie; Bonilla, Carolina; Richardson, William; Hamilton, Georgina L; Ekwall, Karl; McLaughlin, Paul J; Allshire, Robin C (2007). "A NASP (N1/N2)-Related Protein, Sim3, Binds CENP-A and is Required for Its Deposition at Fission Yeast Centromeres". Molecular Cell. 28 (6): 1029–44. doi:10.1016/j.molcel.2007.10.010. PMC 2193228. PMID 18158900.
  27. ^ Pidoux, Alison L; Choi, Eun Shik; Abbott, Johanna K.R; Liu, Xingkun; Kagansky, Alexander; Castillo, Araceli G; Hamilton, Georgina L; Richardson, William; Rappsilber, Juri; He, Xiangwei; Allshire, Robin C (2009). "Fission Yeast Scm3: A CENP-A Receptor Required for Integrity of Subkinetochore Chromatin". Molecular Cell. 33 (3): 299–311. doi:10.1016/j.molcel.2009.01.019. PMC 2697330. PMID 19217404.
  28. ^ Sanchez-Pulido, Luis; Pidoux, Alison L; Ponting, Chris P; Allshire, Robin C (2009). "Common Ancestry of the CENP-A Chaperones Scm3 and HJURP". Cell. 137 (7): 1173–4. doi:10.1016/j.cell.2009.06.010. PMC 4397584. PMID 19563746.
  29. ^ Subramanian, L; Toda, N. R. T; Rappsilber, J; Allshire, R. C (2014). "Eic1 links Mis18 with the CCAN/Mis6/Ctf19 complex to promote CENP-A assembly". Open Biology. 4 (4): 140043. doi:10.1098/rsob.140043. PMC 4043117. PMID 24789708.
  30. ^ Folco, H. D; Pidoux, A. L; Urano, T; Allshire, R. C (2008). "Heterochromatin and RNAi Are Required to Establish CENP-A Chromatin at Centromeres". Science. 319 (5859): 94–7. Bibcode:2008Sci...319...94F. doi:10.1126/science.1150944. PMC 2586718. PMID 18174443.
  31. ^ Kagansky, A; Folco, H. D; Almeida, R; Pidoux, A. L; Boukaba, A; Simmer, F; Urano, T; Hamilton, G. L; Allshire, R. C (2009). "Synthetic Heterochromatin Bypasses RNAi and Centromeric Repeats to Establish Functional Centromeres". Science. 324 (5935): 1716–9. Bibcode:2009Sci...324.1716K. doi:10.1126/science.1172026. PMC 2949999. PMID 19556509.
  32. ^ Partridge, J. F; Borgstrøm, B; Allshire, R. C (2000). "Distinct protein interaction domains and protein spreading in a complex centromere". Genes & Development. 14 (7): 783–91. doi:10.1101/gad.14.7.783. PMC 316498. PMID 10766735.
  33. ^ Trewick, Sarah C; Minc, Elsa; Antonelli, Richard; Urano, Takeshi; Allshire, Robin C (2007). "The JmjC domain protein Epe1 prevents unregulated assembly and disassembly of heterochromatin". The EMBO Journal. 26 (22): 4670–82. doi:10.1038/sj.emboj.7601892. PMC 2048757. PMID 17948055.
  34. ^ Buscaino, Alessia; Lejeune, Erwan; Audergon, Pauline; Hamilton, Georgina; Pidoux, Alison; Allshire, Robin C (2013). "Distinct roles for Sir2 and RNAi in centromeric heterochromatin nucleation, spreading and maintenance". The EMBO Journal. 32 (9): 1250–64. doi:10.1038/emboj.2013.72. PMC 3642681. PMID 23572080.
  35. ^ Audergon, P. N. C. B; Catania, S; Kagansky, A; Tong, P; Shukla, M; Pidoux, A. L; Allshire, R. C (2015). "Restricted epigenetic inheritance of H3K9 methylation". Science. 348 (6230): 132–5. Bibcode:2015Sci...348..132A. doi:10.1126/science.1260638. PMC 4397586. PMID 25838386.
  36. ^ Simmer, Femke; Buscaino, Alessia; Kos-Braun, Isabelle C; Kagansky, Alexander; Boukaba, Abdelhalim; Urano, Takeshi; Kerr, Alastair R W; Allshire, Robin C (2010). "Hairpin RNA induces secondary small interfering RNA synthesis and silencing in trans in fission yeast". EMBO Reports. 11 (2): 112–8. doi:10.1038/embor.2009.273. PMC 2828748. PMID 20062003.
  37. ^ Bayne, Elizabeth H; White, Sharon A; Kagansky, Alexander; Bijos, Dominika A; Sanchez-Pulido, Luis; Hoe, Kwang-Lae; Kim, Dong-Uk; Park, Han-Oh; Ponting, Chris P; Rappsilber, Juri; Allshire, Robin C (2010). "Stc1: A Critical Link between RNAi and Chromatin Modification Required for Heterochromatin Integrity". Cell. 140 (5): 666–77. doi:10.1016/j.cell.2010.01.038. PMC 2875855. PMID 20211136.
  38. ^ Buscaino, Alessia; White, Sharon A; Houston, Douglas R; Lejeune, Erwan; Simmer, Femke; De Lima Alves, Flavia; Diyora, Piyush T; Urano, Takeshi; Bayne, Elizabeth H; Rappsilber, Juri; Allshire, Robin C (2012). "Raf1 is a DCAF for the Rik1 DDB1-Like Protein and Has Separable Roles in siRNA Generation and Chromatin Modification". PLOS Genetics. 8 (2): e1002499. doi:10.1371/journal.pgen.1002499. PMC 3271066. PMID 22319459.
  39. ^ Bayne, E. H; Portoso, M; Kagansky, A; Kos-Braun, I. C; Urano, T; Ekwall, K; Alves, F; Rappsilber, J; Allshire, R. C (2008). "Splicing Factors Facilitate RNAi-Directed Silencing in Fission Yeast". Science. 322 (5901): 602–6. Bibcode:2008Sci...322..602B. doi:10.1126/science.1164029. PMC 2585287. PMID 18948543.
  40. ^ Bayne, Elizabeth H; Bijos, Dominika A; White, Sharon A; Alves, Flavia de Lima; Rappsilber, Juri; Allshire, Robin C (2014). "A systematic genetic screen identifies new factors influencing centromeric heterochromatin integrity in fission yeast". Genome Biology. 15 (10): 481. doi:10.1186/s13059-014-0481-4. PMC 4210515. PMID 25274039.
  41. ^ Choi, Eun Shik; Strålfors, Annelie; Castillo, Araceli G; Durand-Dubief, Mickaël; Ekwall, Karl; Allshire, Robin C (2011). "Identification of Noncoding Transcripts from within CENP-A Chromatin at Fission Yeast Centromeres". Journal of Biological Chemistry. 286 (26): 23600–7. doi:10.1074/jbc.M111.228510. PMC 3123123. PMID 21531710.
  42. ^ Choi, Eun Shik; Strålfors, Annelie; Catania, Sandra; Castillo, Araceli G; Svensson, J. Peter; Pidoux, Alison L; Ekwall, Karl; Allshire, Robin C (2012). "Factors That Promote H3 Chromatin Integrity during Transcription Prevent Promiscuous Deposition of CENP-ACnp1 in Fission Yeast". PLOS Genetics. 8 (9): e1002985. doi:10.1371/journal.pgen.1002985. PMC 3447972. PMID 23028377.
  43. ^ Catania, Sandra; Pidoux, Alison L; Allshire, Robin C (2015). "Sequence Features and Transcriptional Stalling within Centromere DNA Promote Establishment of CENP-A Chromatin". PLOS Genetics. 11 (3): e1004986. doi:10.1371/journal.pgen.1004986. PMC 4349457. PMID 25738810.
  44. ^ Shukla M, Manu; Allshire, Robin C (2018). "Centromere DNA Destabilizes H3 Nucleosomes to Promote CENP-A Deposition during the Cell Cycle". Current Biology. 28 (24): 3924–3936. doi:10.1016/j.cub.2018.10.049. PMC 6303189. PMID 30503616.
  45. ^ Ard, Ryan; Tong, Pin; Allshire, Robin C (2014). "Long non-coding RNA-mediated transcriptional interference of a permease gene confers drug tolerance in fission yeast". Nature Communications. 5: 5576. Bibcode:2014NatCo...5.5576A. doi:10.1038/ncomms6576. PMC 4255232. PMID 25428589.
  46. ^ Ard, Ryan; Allshire, Robin C (2016). "Transcription-coupled changes to chromatin underpin gene silencing by transcriptional interference". Nucleic Acids Research. 44 (22): 10619–10630. doi:10.1093/nar/gkw801. PMC 5159543. PMID 27613421.
  47. ^ Torres-Garcia, Sito (2020). "Epigenetic gene silencing by heterochromatin primes fungal resistance". Nature. 585 (7825): 453–458. Bibcode:2020Natur.585..453T. doi:10.1038/s41586-020-2706-x. PMC 7116710. PMID 32908306.
  48. ^ "biography". ICG. Retrieved 4 December 2018.
  49. ^ Anon (2011). "Professor Robin Allshire FRS". royalsociety.org. One or more of the preceding sentences incorporates text from the royalsociety.org website where:

    “All text published under the heading 'Biography' on Fellow profile pages is available under Creative Commons Attribution 4.0 International License.” --Royal Society Terms, conditions and policies at the Wayback Machine (archived 2016-11-11)

  50. ^ "Professor Robin Allshire | the Academy of Medical Sciences". Academy of Medical Sciences.
  51. ^ "Genetics Society Medal 2013". Genetics Society. Retrieved 4 December 2018.

 This article incorporates text available under the CC BY 4.0 license.