![Greg Ngo](https://profiles-cardiff.imgix.net/attachments/2527?w=200&h=200&auto=format&crop=faces&fit=crop&q=90")
Trosolwyg
R-dolenni & Labordy Sefydlogrwydd Genom
Mae fy ymchwil cyfredol yn canolbwyntio ar ddeall ffurfiad R-ddolen, strwythurau enigmatig sy'n cynnwys hybridau DNA-RNA, mewn seibiannau llinyn dwbl DNA, a sut mae'r broses hon yn effeithio ar sefydlogrwydd genomau.
Mae un prosiect mawr yn y labordy yn cynnwys ymchwilio i rolau dolenni R a sefydlogrwydd genomau ym pathogenesis anhwylderau niwroddatblygiadol megis anabledd deallusol, anhwylder ar y sbectrwm awtistiaeth (ASD) ac anhwylder gorfywiog diffyg sylw (ADHD). Rydym yn cael ein hariannu'n bennaf gan Wobr Datblygu Gyrfa Ymddiriedolaeth Wellcome.
Cyhoeddiad
2022
- Parker, C. et al. 2022. BCL-3 loss sensitises colorectal cancer cells to DNA damage by targeting homologous recombination. DNA Repair 115, article number: 103331. (10.1016/j.dnarep.2022.103331)
2021
- Ngo, G. H. P., Grimstead, J. W. and Baird, D. M. 2021. UPF1 promotes the formation of R loops to stimulate DNA double-strand break repair. Nature Communications 12, article number: 3849. (10.1038/s41467-021-24201-w)
2018
- Ngo, G., Hyatt, S., Grimstead, J., Jones, R., Hendrickson, E., Pepper, C. and Baird, D. 2018. PARP inhibition prevents escape from a telomere-driven crisis and inhibits cell immortalisation. Oncotarget 9(101), pp. 37549-37563. (10.18632/oncotarget.26499)
2017
- Wardell, K., Haldenby, S., Jones, N., Liddell, S., Ngo, G. and Allers, T. 2017. RadB acts in homologous recombination in the archaeon Haloferax volcanii, consistent with a role as recombination mediator. DNA Repair 55, pp. 7-16. (10.1016/j.dnarep.2017.04.005)
- Holstein, E., Ngo, G., Lawless, C., Banks, P., Greetham, M., Wilkinson, D. and Lydall, D. 2017. Systematic analysis of the DNA damage response network in telomere defective budding yeast. G3: Genes | Genomes | Genetics 7(7), pp. 2375. (10.1534/g3.117.042283)
2015
- Ngo, G. H. and Lydall, D. 2015. The 9-1-1 checkpoint clamp coordinates resection at DNA double strand breaks. Nucleic Acids Research 43(10), pp. 5017–5032. (10.1093/nar/gkv409)
2014
- Ngo, G. H., Balakrishnan, L., Dubarry, M., Campbell, J. L. and Lydall, D. 2014. The 9-1-1 checkpoint clamp stimulates DNA resection by Dna2-Sgs1 and Exo1. Nucleic Acids Research 42(16), pp. 10516–10528. (10.1093/nar/gku746)
2011
- Addinall, S. G. et al. 2011. Quantitative fitness analysis shows that NMD proteins and many other protein complexes suppress or enhance distinct telomere cap defects. PLoS Genetics 7(4), article number: e1001362. (10.1371/journal.pgen.1001362)
2010
- Ngo, G. and Lydall, D. 2010. Survival and growth of yeast without telomere capping by Cdc13 in the absence of Sgs1, Exo1, and Rad9. PLoS Genetics 6(8), article number: e1001072. (10.1371/journal.pgen.1001072)
2009
- Matic, I., Delmas, S., Shunburne, L., Ngo, H. and Allers, T. 2009. Mre11-Rad50 promotes rapid repair of DNA damage in the Polyploid Archaeon Haloferax volcanii by restraining homologous recombination. PLoS Genetics 5(7), article number: 1000552. (10.1371/journal.pgen.1000552)
- Mankouri, H. W., Ngo, G. and Hickson, I. D. 2009. Esc2 and Sgs1 Act in Functionally Distinct Branches of the Homologous Recombination Repair Pathway inSaccharomyces cerevisiae. Molecular Biology of the Cell 20(6), pp. 1683-1694. (10.1091/mbc.e08-08-0877)
2008
- Morin, I., Ngo, H. P., Greenall, A., Zubko, M. K., Morrice, N. and Lydall, D. 2008. Checkpoint-dependent phosphorylation of Exo1 modulates the DNA damage response. The EMBO Journal 27(18), pp. 2400-2410. (10.1038/emboj.2008.171)
2007
- Mankouri, H. W., Ngo, G. and Hickson, I. D. 2007. Shu proteins promote the formation of homologous recombination intermediates that are processed by sgs1-rmi1-top3. Molecular Biology of the Cell 18(10), pp. 3711-4200. (10.1091/mbc.e07-05-0490)
2004
- Allers, T., Ngo, H. P., Mevarech, M. and Lloyd, R. G. 2004. Development of Additional Selectable Markers for the Halophilic Archaeon Haloferax volcanii Based on the leuB and trpA Genes. Applied and Environmental Microbiology 70(2), pp. 943-953. (10.1128/AEM.70.2.943-953.2004)
2003
- Allers, T. and Ngo, H. 2003. Genetic analysis of homologous recombination in Archaea: Haloferax volcanii as a model organism. Biochemical Society Transactions 31(3), pp. 706-710. (10.1042/bst0310706)
- Moore, T., McGlynn, P., Ngo, H. P., Sharples, G. and Lloyd, R. 2003. The RdgC protein of Escherichia coli binds DNA and counters a toxic effect of RecFOR in strains lacking the replication restart protein PriA. The EMBO Journal 22(3), pp. 735-745. (10.1093/emboj/cdg048)
Articles
- Parker, C. et al. 2022. BCL-3 loss sensitises colorectal cancer cells to DNA damage by targeting homologous recombination. DNA Repair 115, article number: 103331. (10.1016/j.dnarep.2022.103331)
- Ngo, G. H. P., Grimstead, J. W. and Baird, D. M. 2021. UPF1 promotes the formation of R loops to stimulate DNA double-strand break repair. Nature Communications 12, article number: 3849. (10.1038/s41467-021-24201-w)
- Ngo, G., Hyatt, S., Grimstead, J., Jones, R., Hendrickson, E., Pepper, C. and Baird, D. 2018. PARP inhibition prevents escape from a telomere-driven crisis and inhibits cell immortalisation. Oncotarget 9(101), pp. 37549-37563. (10.18632/oncotarget.26499)
- Wardell, K., Haldenby, S., Jones, N., Liddell, S., Ngo, G. and Allers, T. 2017. RadB acts in homologous recombination in the archaeon Haloferax volcanii, consistent with a role as recombination mediator. DNA Repair 55, pp. 7-16. (10.1016/j.dnarep.2017.04.005)
- Holstein, E., Ngo, G., Lawless, C., Banks, P., Greetham, M., Wilkinson, D. and Lydall, D. 2017. Systematic analysis of the DNA damage response network in telomere defective budding yeast. G3: Genes | Genomes | Genetics 7(7), pp. 2375. (10.1534/g3.117.042283)
- Ngo, G. H. and Lydall, D. 2015. The 9-1-1 checkpoint clamp coordinates resection at DNA double strand breaks. Nucleic Acids Research 43(10), pp. 5017–5032. (10.1093/nar/gkv409)
- Ngo, G. H., Balakrishnan, L., Dubarry, M., Campbell, J. L. and Lydall, D. 2014. The 9-1-1 checkpoint clamp stimulates DNA resection by Dna2-Sgs1 and Exo1. Nucleic Acids Research 42(16), pp. 10516–10528. (10.1093/nar/gku746)
- Addinall, S. G. et al. 2011. Quantitative fitness analysis shows that NMD proteins and many other protein complexes suppress or enhance distinct telomere cap defects. PLoS Genetics 7(4), article number: e1001362. (10.1371/journal.pgen.1001362)
- Ngo, G. and Lydall, D. 2010. Survival and growth of yeast without telomere capping by Cdc13 in the absence of Sgs1, Exo1, and Rad9. PLoS Genetics 6(8), article number: e1001072. (10.1371/journal.pgen.1001072)
- Matic, I., Delmas, S., Shunburne, L., Ngo, H. and Allers, T. 2009. Mre11-Rad50 promotes rapid repair of DNA damage in the Polyploid Archaeon Haloferax volcanii by restraining homologous recombination. PLoS Genetics 5(7), article number: 1000552. (10.1371/journal.pgen.1000552)
- Mankouri, H. W., Ngo, G. and Hickson, I. D. 2009. Esc2 and Sgs1 Act in Functionally Distinct Branches of the Homologous Recombination Repair Pathway inSaccharomyces cerevisiae. Molecular Biology of the Cell 20(6), pp. 1683-1694. (10.1091/mbc.e08-08-0877)
- Morin, I., Ngo, H. P., Greenall, A., Zubko, M. K., Morrice, N. and Lydall, D. 2008. Checkpoint-dependent phosphorylation of Exo1 modulates the DNA damage response. The EMBO Journal 27(18), pp. 2400-2410. (10.1038/emboj.2008.171)
- Mankouri, H. W., Ngo, G. and Hickson, I. D. 2007. Shu proteins promote the formation of homologous recombination intermediates that are processed by sgs1-rmi1-top3. Molecular Biology of the Cell 18(10), pp. 3711-4200. (10.1091/mbc.e07-05-0490)
- Allers, T., Ngo, H. P., Mevarech, M. and Lloyd, R. G. 2004. Development of Additional Selectable Markers for the Halophilic Archaeon Haloferax volcanii Based on the leuB and trpA Genes. Applied and Environmental Microbiology 70(2), pp. 943-953. (10.1128/AEM.70.2.943-953.2004)
- Allers, T. and Ngo, H. 2003. Genetic analysis of homologous recombination in Archaea: Haloferax volcanii as a model organism. Biochemical Society Transactions 31(3), pp. 706-710. (10.1042/bst0310706)
- Moore, T., McGlynn, P., Ngo, H. P., Sharples, G. and Lloyd, R. 2003. The RdgC protein of Escherichia coli binds DNA and counters a toxic effect of RecFOR in strains lacking the replication restart protein PriA. The EMBO Journal 22(3), pp. 735-745. (10.1093/emboj/cdg048)
Ymchwil
Mae gen i ddiddordeb hirsefydlog mewn atgyweirio DNA a'i gyfraniad at sefydlogrwydd genomau, gan ganolbwyntio ar atgyweirio seibiannau dwbl-llinyn DNA (DSBs) a telomeres camweithredol. Dros yr 20 mlynedd diwethaf, rwyf wedi datblygu arbenigedd unigryw wrth ddadansoddi canolradd / cynhyrchion atgyweirio DNA ac wedi cyfrannu at ddealltwriaeth o wahanol fecanweithiau atgyweirio DNA mewn bodau dynol ac organebau model (burum newydd, archaea, a bacteria).
Yn fwy diweddar, rwyf wedi dod â diddordeb yn rôl hybrid DNA-RNA mewn atgyweirio DNA, yn dilyn fy darganfyddiad bod dolenni R yn cronni yn DSBs. Ar ben hynny, darganfyddais fod dau enyn, UPF1 ac UPF3B, yn ysgogi ffurfio'r strwythurau enigmatig hyn mewn celloedd dynol. Mae intriguingly, camweithrediad yn UPF1 ac UPF3B yn gysylltiedig â risg etifeddol ar gyfer datblygu anhwylderau niwroddatblygiadol.
Fy nodau ymchwil yw sefydlu'r mecanweithiau moleciwlaidd sy'n hyrwyddo ffurfio dolen R yn DSBs a deall sut mae'r strwythurau hyn yn effeithio ar sefydlogrwydd genom a datblygu anhwylderau niwroddatblygiadol. I wneud hyn, rydym yn defnyddio dull amlddisgyblaethol sy'n cyfuno geneteg, biocemeg, biowybodeg a niwrowyddoniaeth. Ymhlith y technegau allweddol a ddefnyddiwn mae golygu genynnau CRISPR, ymhelaethu meintiol o DNA un-llinyn (QAOS), electrofforesis gel DNA dau ddimensiwn, dadansoddiad amplicon PCR un moleciwl, dilyniannu'r genhedlaeth nesaf (NGS), dilyniannu nanopore hir-ddarllen, mapio DSB (INDUCE-seq), a thechnolegau bôn-gelloedd pluripotent a ysgogwyd.
Aelodau'r Lab
Dr Siamak Kamranvar
Dr Ashley Parkes
Bywgraffiad
Taniodd fy niddordeb mewn sefydlogrwydd genomau yn ystod fy mhrosiect israddedig, lle'r oeddwn yn astudio mwtanau atgyweirio DNA yn E. coli o dan arweiniad yr Athro Robert Lloyd ym Mhrifysgol Nottingham. Fel cynorthwyydd ymchwil i Dr. Thorsten Allers, hefyd ym Mhrifysgol Nottingham, newidiais i weithio ar yr archaeon H. volcanii, gan gyfrannu at ddatblygu offer genetig i ymchwilio i ailgyfuniad homologous (AD).
Yn dilyn hynny, yn ystod fy astudiaethau D.Phil. o dan fentoriaeth yr Athro Ian Hickson ym Mhrifysgol Rhydychen, fe wnes i nodweddu genynnau sy'n rhyngweithio'n enetig â'r Bloom helicase (Sgs1) mewn burum egin. Arweiniodd yr ymchwil hon at adnabod Esc2 fel ffactor newydd sy'n hanfodol ar gyfer AD mewn ffyrc dyblygu stondin.
Ar ôl cwblhau fy D.Phil., ymunais â labordy'r Athro David Lydall ym Mhrifysgol Newcastle i archwilio mecanwaith atgyweirio DNA mewn telomerau heb eu capio mewn burum newydd. Mae fy ngwaith yn taflu goleuni ar rôl hanfodol ail-dorri DNA mewn senescence cellog, gan ddatgelu ei reoleiddio cymhleth gan wahanol broteinau checkpoint difrod DNA.
Parhaodd fy nhaith ymchwil ym Mhrifysgol Caerdydd, lle ymunais â labordy yr Athro Duncan Baird i ymchwilio i atgyweirio DNA telomerig mewn celloedd dynol. Trwy fy astudiaethau, dangosais fod atalyddion PARP yn dileu celloedd yn ddetholus yn ystod argyfwng telomere, gan gyflwyno llwybr addawol ar gyfer atal anfarwoli celloedd ac atal dilyniant canser. Yn ddiweddar, gwnes i ddarganfyddiad arloesol trwy ganfod dolenni R yn uniongyrchol mewn seibiannau llinyn dwbl DNA (DSBs) am y tro cyntaf, gan ddatgelu eu cenhedlaeth gan UPF1 i ysgogi atgyweirio DNA.
Yn 2023, dyfarnwyd Gwobr Datblygu Gyrfa Ymddiriedolaeth Wellcome i mi ymchwilio i rolau R-dolenni a mwtaniadau ym pathogenesis anhwylderau niwroddatblygiadol.
Meysydd goruchwyliaeth
Mae gen i ddiddordeb mewn goruchwylio myfyrwyr PhD ym meysydd:
- Sefydlogrwydd genom
- Atgyweirio DNA
- Anhwylderau niwroddatblygiadol
Goruchwyliaeth gyfredol
Angelos Damo
Contact Details
Adeilad Geneteg Canser, Ysbyty Athrofaol Cymru, Parc y Mynydd Bychan, Caerdydd, CF14 4XN
