Robin Allshire

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

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

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

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

  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.

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