Previous Events

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This Friday we will have a very special seminar at 11am in the Smurfit Atrium. (*Note the change of time).

Gero Miesenböck FRS is being conferred an Honorary Degree - Doctor in Science (honoris causa) by Trinity College on Friday and has kindly agreed to speak to the students, researchers and staff on his pioneering work (https://en.wikipedia.org/wiki/Gero_Miesenböck [en.wikipedia.org]). All teaching in the Smurfit Institute of Genetics is cancelled from 11am-12pm to allow staff and students attend this special seminar.

The title of his seminar will be: ‘Optogenetics’.

Special notes on this week’s speaker, Professor Gero Miesenböck:

Gero Miesenböck pioneered the science of optogenetics for which there will be Nobel Prize awarded in coming years. He established the principles of optogenetic control in 2002, using light to activate normally light-insensitive neurons and thereby allow remote control animal behaviour.  Optogenetics, by allowing identified neurons to be selectively activated or silenced by light, has revolutionized our ability to understand and dissect brain circuits.

Miesenböck has exploited optogenetics in a succession of brilliant experiments illuminating synaptic connectivity, the neural basis of reward, mechanisms of sleep homeostasis and the control of sexually dimorphic circuitry. These incisive analyses have demonstrated the full potential of optogenetics beyond the proof-of-principle stage, providing a tool for the treatment of acute Parkinsonism, depression and other neurological conditions.

He has received several individual awards for his work (FRS, the William Exner Medal, the Heinrich Wieland Prize) and shared several major prizes (E.g. The Brain Prize, The Jakob Heskay Gabbay Award, the BBVA Foundation Frontiers of Knowledge Award, The Massry Prize) with one or more of among Ernst Bamberg, Edward Boyden, Karl Deisseroth, Peter Hegemann, and Georg Nagel, who are the others on the short list for the Optogenetics Nobel Prize.

Selected Papers:

• Sjulson L, Cassataro D, DasGupta S and Miesenböck G., 2016. Cell-Specific Targeting of Genetically Encoded Tools for Neuroscience. Annu Rev Genet. 50:571-594.
• Pimentel D, Donlea JM, Talbot CB, Song SM, Thurston AJF and Miesenböck G., 2016. Operation of a homeostatic sleep switch. Nature. 536(7616):333-337.
• Adamantidis A et al., 2015. Optogenetics: 10 years after ChR2 in neurons--views from the community.   Nat Neurosci. 18(9):1202-12
• DasGupta S, Ferreira CH and Miesenböck G., 2014. FoxP influences the speed and accuracy of a perceptual decision in Drosophila.  Science. 344(6186):901-4.

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Adrian Bracken has invited Dr. Sara Farrona from NUI Galway to give a seminar Friday 9th October 1:00pm in The Smurfit Atrium (please note the time).

The title of her seminar will be: 'Identification of novel components of the Polycomb Group pathway in Arabidopsis'.

Sara is a plant geneticist who studies the function chromatin regulators. During her PhD she studied the function ofBRM, a protein involved in chromatin remodeling that has an important role in plant development. This research showed her that flowering, one of the major developmental processes of plants, is a wonderful model to extend her studies on chromatin regulation. After her PhD, she continued this line of research in her postdoctorate and now as a newly established principal investigator in NUI Galway.

Selected publications:

Post-fertilization expression of FLOWERING LOCUS T suppresses reproductive reversion.
Liu L, Farrona S, Klemme S, Turck FK.
Front Plant Sci. 2014 Apr 30;5:164.

Development-related PcG target in the apex 4 controls leaf margin architecture in Arabidopsis thaliana.
Engelhorn J, Reimer JJ, Leuz I, Göbel U, Huettel B, Farrona S, Turck F.
Development. 2012 Jul;139(14):2566-75.

CDKF;1 and CDKD protein kinases regulate phosphorylation of serine residues in the C-terminal domain of Arabidopsis RNA polymerase II.
Hajheidari M, Farrona S, Huettel B, Koncz Z, Koncz C.
Plant Cell. 2012 Apr;24(4):1626-42.

Tissue-specific expression of FLOWERING LOCUS T in Arabidopsis is maintained independently of polycomb group protein repression.
Farrona S, Thorpe FL, Engelhorn J, Adrian J, Dong X, Sarid-Krebs L, Goodrich J, Turck F.
Plant Cell. 2011 Sep;23(9):3204-14.

Brahma is required for proper expression of the floral repressor FLC in Arabidopsis.
Farrona S, Hurtado L, March-Díaz R, Schmitz RJ, Florencio FJ, Turck F, Amasino RM, Reyes JC.
PLoS One. 2011 Mar 21;6(3):e17997.

cis-Regulatory elements and chromatin state coordinately control temporal and spatial expression of FLOWERING LOCUS T in Arabidopsis.
Adrian J, Farrona S*, Reimer JJ, Albani MC, Coupland G, Turck F.
Plant Cell. 2010 May;22(5):1425-40. (* = joint firstauthor)

CHD3 proteins and polycomb group proteins antagonistically determine cell identity in Arabidopsis.
Aichinger E, Villar CB, Farrona S, Reyes JC, Hennig L, Köhler C.
PLoS Genet. 2009 Aug;5(8):e1000605.

PEP1 regulates perennial flowering in Arabis alpina.
Wang R, Farrona S, Vincent C, Joecker A, Schoof H, Turck F, Alonso-Blanco C, Coupland G, Albani MC.
Nature. 2009 May 21;459(7245):423-7.

The impact of chromatin regulation on the floral transition.
Farrona S, Coupland G, Turck F.
Semin Cell Dev Biol. 2008 Dec;19(6):560-73.

A nucleosome interaction module is required for normal function of Arabidopsis thaliana BRAHMA.
Farrona S, Hurtado L, Reyes JC. J Mol
Biol. 2007 Oct 19;373(2):240-50.

Arabidopsis TFL2/LHP1 specifically associates with genes marked by trimethylation of histone H3 lysine 27.
Turck F, Roudier F, Farrona S, Martin-Magniette ML, Guillaume E, Buisine N, Gagnot S, Martienssen RA, Coupland G, Colot V.
PLoS Genet. 2007 Jun;3(6):e86.

FT protein movement contributes to long-distance signaling in floral induction of Arabidopsis.
Corbesier L, Vincent C, Jang S, Fornara F, Fan Q, Searle I, Giakountis A, Farrona S, Gissot L, Turnbull C, Coupland G.
Science. 2007 May 18;316(5827):1030-3.

The putative SWI/SNF complex subunit BRAHMA activates flower homeotic genes in Arabidopsis thaliana.
Hurtado L, Farrona S, Reyes JC. Plant Mol Biol. 2006 Sep;62(1-2):291-304.

The Arabidopsis thaliana SNF2 homolog AtBRM controls shoot development and flowering. Farrona S, Hurtado L, Bowman JL, Reyes JC.
Development. 2004 Oct;131(20):4965-75.

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Kevin Mitchell has invited Dr. Denis Jabaudon from the University of Geneva to give a seminar on Thursday at 2:00pm in The Smurfit Atrium (please note the time).

The title of his seminar will be: 'Becoming a new neuron in the cerebral cortex'.

Denis is a leading researcher in developmental neurobiology and is interested in the mechanisms of specification of neuronal cell fates in the developing brain. In particular, his group has elucidated some of the mechanisms by which incoming axons from thalamus to cortex (or retina to thalamus) instruct the cellular identity of neurons in the recipient areas. This ongoing interplay between cell fates and connectivity patterns is a fundamental process in the self-assembly and refinement of the brain's circuitry.

Selected publications:

Modality-specific thalamocortical inputs instruct the identity of postsynaptic L4 neurons.
Pouchelon G, Gambino F, Bellone C, Telley L, Vitali I, Lüscher C, Holtmaat A, Jabaudon D.
Nature. 2014 Jul 24;511(7510):471-4.

Retinal input directs the recruitment of inhibitory interneurons into thalamic visual circuits.
Golding B, Pouchelon G, Bellone C, Murthy S, Di Nardo AA, Govindan S, Ogawa M, Shimogori T, Lüscher C, Dayer A, Jabaudon D.
Neuron. 2014 Mar 5;81(5):1057-69.

In vivo reprogramming of circuit connectivity in postmitotic neocortical neurons.
De la Rossa A, Bellone C, Golding B, Vitali I, Moss J, Toni N, Lüscher C, Jabaudon D.
Nat Neurosci. 2013 Feb;16(2):193-200.

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Research Interests:

The major focus of the research in Prof. Helin?s laboratory is to elucidate the molecular mechanisms leading to cancer and to transform this knowledge into novel anti-cancer therapies. This research has led to the identification of novel mechanisms for the control of stem cell self-renewal and differentiation, the identification of novel enzymatic activities regulating histone methylation, and to important new insights into how cancer develops. Moreover the discoveries have led to the foundation of the biotech company EpiTherapeutics that develops small molecule inhibitors for the future treatment of cancer patients.

Selected Publications:

shRNA screening identifies JMJD1C as being required for leukemia maintenance.
Sroczynska P, Cruickshank VA, Bukowski JP, Miyagi S, Bagger FO, Walfridsson J, Schuster MB, Porse B, Helin K.
Blood. 2014 Feb 5.

The histone demethylase Jarid1b ensures faithful mouse development by protecting developmental genes from aberrant H3K4me3.
Albert M, Schmitz SU, Kooistra SM, Malatesta M, Morales Torres C, Rekling JC, Johansen JV, Abarrategui I, Helin K.
PLoS Genet. 2013 Apr;9(4):e1003461. doi: 10.1371/journal.pgen.1003461. Epub 2013 Apr 18.

Fbxl10/Kdm2b recruits polycomb repressive complex 1 to CpG islands and regulates H2A ubiquitylation.
Wu X, Johansen JV, Helin K.
Mol Cell. 2013 Mar 28;49(6):1134-46.

TET1 and hydroxymethylcytosine in transcription and DNA methylation fidelity.
Williams K, Christensen J, Pedersen MT, Johansen JV, Cloos PA, Rappsilber J, Helin K.
Nature. 2011 May 19;473(7347):343-8.

A Functional Link between the Histone Demethylase PHF8 and the Transcription Factor ZNF711 in X-Linked Mental Retardation.
Kleine-Kohlbrecher D, Christensen J, Vandamme J, Abarrategui I, Bak M, Tommerup N, Shi X, Gozani O, Rappsilber J, Salcini AE, Helin K (2010).
Mol Cell 38(2):165-178.

JARID2 regulates binding of the Polycomb repressive complex 2 to target genes in ES cells.
Pasini D, Cloos PA, Walfridsson J, Olsson L, Bukowski JP, Johansen JV, Bak M, Tommerup N, Rappsilber J, Helin K (2010).
Nature 464, 306-310.

NEK11 regulates CDC25A degradation and the IR-induced G2/M checkpoint.
Melixetian M, Klein DK, S?rensen CS and Helin K (2009).
Nature Cell Biology 11, 1247-1253.

The H3K27me3 demethylase JMJD3 contributes to the activation of the INK4A-ARF locus in response to oncogene- and stress-induced senescence.
Agger K, Cloos PA, Rudkjaer L, Williams K, Andersen G, Christensen J and Helin K (2009).
Genes Dev 23, 1171-1176.

A model for transmission of the H3K27me3 epigenetic mark.
Hansen KH, Adrian Bracken A, Pasini D, Gehani SS, Dietrich N, Monrad A, Rappsilber J, Lerdrup M and Helin K (2008).
Nature Cell Biology 10, 1291-1300.

Functional interaction between the RBP2 H3K4 demethylase and the Polycomb Repressive Complex 2.
Pasini D, Hansen KH, Christensen J, Agger K, Cloos PA and Helin K (2008).
Genes Dev 22, 1345-1355.

UTX and JMJD3 are H3K27 demethylases involved in HOX gene regulation and development.
Agger K, Christensen J, Cloos PA, Pasini D, Rose S, Rappsilber J, Issaeva I, Canaani E, Salcini AE and Helin K (2007).
Nature 449, 731-734.

The Polycomb group proteins bind throughout the INK4A-ARF locus and are dissociated in senescent cells.
Bracken AP, Kleine-Kohlbrecher D, Dietrich N, Pasini D, Gargiulo G, Beekman C, Theilgaard-M?nch K, Minucci S, Porse BT, Marine JC, Hansen KH and Helin K (2007).
Genes Dev 21, 525-530.

RBP2 belongs to a family of demethylases specific for tri- and di-methylated lysine 4 on Histone 3.
Christensen J, Agger K, Cloos P, Pasini D, Rose S, Sennels L, Rappsilber J, Hansen KH, Salcini AE and Helin K (2007).
Cell, 128, 1063-1076.

Genome-wide mapping of Polycomb target genes unravels their role in cell-fate transitions.
Bracken AP, Dietrich N, Pasini D, Hansen KH and Helin K (2006).
Genes Dev 20, 1123-1136.

The putative oncogene GASC1/JMJD2c demethylates tri- and di-methylated lysine 9 on histone H3.
Cloos PAC, Christensen J, Agger K, Maiolica A, Rappsibler J, Antal T, Hansen KH and Helin K (2006).
Nature 442, 307-311.

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Abstract of Talk:

There is considerable variation in the rate at which different genes evolve. Why is this? Classically it has been considered that the density of functionally important sites must predict rates of protein evolution. Likewise, amino acid choice is usually assumed to reflect optimal protein function and codon choice is random. Here I present evidence suggesting that this view is too simplistic. In particular I concentrate on how selection acting during the protein's production history can also affect gene evolutionary rates as well as amino acid and codon choice. Exploring the role of selection at the RNA level, I specifically address how the need to specify exonic splice enhancer motifs in pre-mRNA impacts amino acid choice, codon choice and rates of evolution at both synonymous and non-synonymous sites. Moreover, I show, in opposition to the nearly neutral theory of molecular evolution, that as regards splicing, selection is stronger, not weaker, when population sizes are small.

Brief Biography:

Laurence Hurst is the Professor of Evolutionary Genetics in the Department of Biology and Biochemistry at The University of Bath. His research interests cover a broad span of evolution, genetics and genomics. His group dominantly uses computational and mathematical techniques to understand the way genes and genomes evolve. He is especially interested in understanding whether selection might operate on what have commonly been assumed to be unimportant mutations (e.g. synonymous mutations, small genome re-arrangements) and if so why. This has relevance for diagnosis of genetic diseases, as well as for gene and genome manipulation (for health, food or research).

Publications:

Laurence is widely considered as one of the international leaders in molecular evolution research. His impressive publication record includes 24 papers in Nature and Nature family (Nat Genet etc.), 3 Science papers and 13 PLoS papers. A full list is available here: http://people.bath.ac.uk/bssldh/LaurenceDHurst/Publications.html

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Adrian Bracken has invited Prof. Haruhiko Koseki a developmental geneticist from the RIKEN Center for Allergy and Immunology in Yokohama, Japan to give a seminar on Friday at 1:00 pm in the Smurfit Atrium.

The title of his seminar will be "Polycomb Silencing in Mammalian Development".

Research interests:

Haruhiko Koseki is Director of the Developmental Genetics Research Group at the RIKEN Research Center for Allergy and Immunology in Yokohama, where he studies the epigenetic regulation of Polycomb group genes in development. He recently joined the journal Development as an Editor. The goal of Dr. Koseki's research is to understand how cellular phenotypes can be stably retained through development irrespective of environmental cues in some situations, while being altered in response to external signals in others. His work also focuses on how these epigenetic mechanisms control morphogenesis and tissue homeostasis. Towards this end, his lab combines mouse genetics, genomic and imaging approaches to study how chromatin modifications regulate stem cell identities, meiosis, patterning and organ development.

Areas of expertise:

Mouse genetics, epigenetics, patterning, meiosis, ES cells, axial specifications

Selected Publications:

Polycomb potentiates meis2 activation in midbrain by mediating interaction of the promoter with a tissue-specific enhancer.
Kondo T, Isono K, Kondo K, Endo TA, Itohara S, Vidal M, Koseki H.
Dev Cell. 2014 Jan 13;28(1):94-101

SAM domain polymerization links subnuclear clustering of PRC1 to gene silencing.
Isono K, Endo TA, Ku M, Yamada D, Suzuki R, Sharif J, Ishikura T, Toyoda T, Bernstein BE, Koseki H.
Dev Cell. 2013 Sep 30;26(6):565-77.

Uhrf1-dependent H3K23 ubiquitylation couples maintenance DNA methylation and replication.
Nishiyama A, Yamaguchi L, Sharif J, Johmura Y, Kawamura T, Nakanishi K, Shimamura S, Arita K, Kodama T, Ishikawa F, Koseki H, Nakanishi M.
Nature. 2013 Oct 10;502(7470):249-53.

Ezh2 augments leukemogenicity by reinforcing differentiation blockage in acute myeloid leukemia.
Tanaka S, Miyagi S, Sashida G, Chiba T, Yuan J, Mochizuki-Kashio M, Suzuki Y, Sugano S, Nakaseko C, Yokote K, Koseki H, Iwama A.
Blood. 2012 Aug 2;120(5):1107-17.

HP1 links histone methylation marks to meiotic synapsis in mice.
Takada Y, Naruse C, Costa Y, Shirakawa T, Tachibana M, Sharif J, Kezuka-Shiotani F, Kakiuchi D, Masumoto H, Shinkai Y, Ohbo K, Peters AH, Turner JM, Asano M, Koseki H.
Development. 2011 Oct;138(19):4207-17.

Mammalian polycomb-like Pcl2/Mtf2 is a novel regulatory component of PRC2 that can differentially modulate polycomb activity both at the Hox gene cluster and at Cdkn2a genes.
Li X, Isono K, Yamada D, Endo TA, Endoh M, Shinga J, Mizutani-Koseki Y, Otte AP, Casanova M, Kitamura H, Kamijo T, Sharif J, Ohara O, Toyada T, Bernstein BE, Brockdorff N, Koseki H.
Mol Cell Biol. 2011 Jan;31(2):351-64.

FGF9 monomer-dimer equilibrium regulates extracellular matrix affinity and tissue diffusion.
Harada M, Murakami H, Okawa A, Okimoto N, Hiraoka S, Nakahara T, Akasaka R, Shiraishi Y, Futatsugi N, Mizutani-Koseki Y, Kuroiwa A, Shirouzu M, Yokoyama S, Taiji M, Iseki S, Ornitz DM, Koseki H.
Nat Genet. 2009 Mar;41(3):289-98.

Polycomb group proteins Ring1A/B are functionally linked to the core transcriptional regulatory circuitry to maintain ES cell identity.
Endoh M, Endo TA, Endoh T, Fujimura Y, Ohara O, Toyoda T, Otte AP, Okano M, Brockdorff N, Vidal M, Koseki H.
Development. 2008 Apr;135(8):1513-24.

The SRA protein Np95 mediates epigenetic inheritance by recruiting Dnmt1 to methylated DNA.
Sharif J, Muto M, Takebayashi S, Suetake I, Iwamatsu A, Endo TA, Shinga J, Mizutani-Koseki Y, Toyoda T, Okamura K, Tajima S, Mitsuya K, Okano M, Koseki H.
Nature. 2007 Dec 6;450(7171):908-12.

Mammalian Polycomb Scmh1 mediates exclusion of Polycomb complexes from the XY body in the pachytene spermatocytes.
Takada Y, Isono K, Shinga J, Turner JM, Kitamura H, Ohara O, Watanabe G, Singh PB, Kamijo T, Jenuwein T, Burgoyne PS, Koseki H.
Development. 2007 Feb;134(3):579-90.

Distinct roles of Polycomb group gene products in transcriptionally repressed and active domains of Hoxb8.
Fujimura Y, Isono K, Vidal M, Endoh M, Kajita H, Mizutani-Koseki Y, Takihara Y, van Lohuizen M, Otte A, Jenuwein T, Deschamps J, Koseki H.
Development. 2006 Jun;133(12):2371-81.

Mammalian polyhomeotic homologues Phc2 and Phc1 act in synergy to mediate polycomb repression of Hox genes.
Isono K, Fujimura Y, Shinga J, Yamaki M, O-Wang J, Takihara Y, Murahashi Y, Takada Y, Mizutani-Koseki Y, Koseki H.
Mol Cell Biol. 2005 Aug;25(15):6694-706.

Mammalian polycomb-mediated repression of Hox genes requires the essential spliceosomal protein Sf3b1.
Isono K, Mizutani-Koseki Y, Komori T, Schmidt-Zachmann MS, Koseki H.
Genes Dev. 2005 Mar 1;19(5):536-41.

Topors, a p53 and topoisomerase I-binding RING finger protein, is a coactivator of p53 in growth suppression induced by DNA damage.
Lin L, Ozaki T, Takada Y, Kageyama H, Nakamura Y, Hata A, Zhang JH, Simonds WF, Nakagawara A, Koseki H.
Oncogene. 2005 May 12;24(21):3385-96.

Involvement of the Polycomb-group gene Ring1B in the specification of the anterior-posterior axis in mice.
Suzuki M, Mizutani-Koseki Y, Fujimura Y, Miyagishima H, Kaneko T, Takada Y, Akasaka T, Tanzawa H, Takihara Y, Nakano M, Masumoto H, Vidal M, Isono K, Koseki H.
Development. 2002 Sep;129(18):4171-83.

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Aoife McLysaght has invited Dr. Andrew Jackson from the School of Natural Sciences in Trinity College to give a seminar on Friday at 1:00 pm in the Smurfit Atrium.

The title of his seminar will be "Evolution of Perception and Behaviour".

Biography:

Dr. Andrew Jackson is a behavioural ecologist and evolutionary biologist in the School of Natural Sciences in Trinity College Dublin. His work focuses on the evolution of social behaviour and includes elements of game theory, comparative approaches, social network analysis, artificial neural networks and genetic algorithms. He also collaborates on more general ecological and health related projects from a theoretical perspective. He graduated in zoology in Trinity College Dublin and did a PhD in theoretical ecology in University of Glasgow before returning to Trinity as a postdoc and then lecturer in 2007.

Relevant Publications:

Healy, K., McNally, L., Ruxton, G.D., Cooper, N. & Jackson, A.L. 2013. Metabolic rate and body size linked with perception of temporal information. Animal Behaviour, 86(4), 685-696 [dx.doi.org].

Wakefield, E.D., Bodey, T.W., Bearhop, S., Blackburn, J., Colhoun, K., Davies, R., Dwyer, R.G., Green, J., Gr?millet, D.,Jackson, A.L., Jessopp, M.J., Kane, A., Langston, R.H.W., Lescro?l, A., Murray, S., Le Nuz, M., Patrick, S.C., P?ron, C., Soanes, L., Wanless, S., Votier, S.C., & Hamer, K.C. 2013. Space Partitioning Without Territoriality in Gannets. Science, 341(6141), 68-70. [dx.doi.org]

McNally, L., Jackson, A.L. 2013. Cooperation creates selection for tactical deception. Proceedings of the Royal Society of London B, 280(1762), [dx.doi.org]

McNally, L., Brown, S.P. & Jackson, A.L. 2012. Cooperation and the evolution of intelligence. Proceedings of the Royal Society of London B, 279, 3027-3034. [dx.doi.org]

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Karsten Hokamp has invited Dr. Anton Enright from the European Bioinformatics Institute, Cambridge, UK to give a seminar on Friday at 1:00 pm in the Smurfit Atrium.

The title of his seminar will be "Small RNAs and their Roles in Genomic Regulation".

Brief Biography:

Anton Enright is a graduate of the Trinity College Genetics department. He first developed his bioinformatics skills as an undergraduate workingwith Prof. Ken Wolfe before moving to the European Bioinformatics Institute in Cambridge for his Ph.D. studies on the computational prediction of protein-protein interactions. His Postdoctoral work was undertaken with Chris Sander at Memorial Sloan-Kettering Cancer Centre in New York. He started his first independent position at the Wellcome Trust Sanger Institute in Cambridge working on computational prediction of the functions of microRNAs. In 2008 he moved back to the European Bioinformatics Institute as a research group leader working on the computational genomics of small RNAs and their roles in various biological systems including early development and the mouse germ line. His talk will focus on the roles of piwiRNAs in regulating transposons in the mouse germ line and discuss other non-coding RNAs including microRNAs and long non-coding RNAs.

Selected Recent Publications:

Kraken: A set of tools for quality control and analysis of high-throughput sequence data.
M Davis, S Dongen, C Abreu-Goodger, N Bartonicek, AJ Enright.
Methods 2013

Multiple epigenetic mechanisms and the piRNA pathway enforce LINE1 silencing during adult spermatogenesis.
Di Giacomo M, Comazzetto S, Saini H, De Fazio S, Carrieri C, Morgan M, Vasiliauskaite L, Benes V, Enright AJ, O'Carroll D.
Mol Cell. 2013

Large-scale analysis of microRNA evolution.
Guerra-Assun??o, J.A. and Enright A.J. (2012).
BMC Genomics 13 (1), 218.

The endonuclease activity of Mili fuels piRNA amplification that silences LINE1 elements.
De Fazio S, Bartonicek N, Di Giacomo M, Abreu-Goodger C, Sankar A, Funaya C, Antony C, Moreira PN, Enright AJ, O'Carroll D.
Nature 2011

An ENU-induced mutation of miR-96 associated with progressive hearing loss in mice.
Lewis MA, Quint E, Glazier AM, Fuchs H, De Angelis MH, Langford C, van Dongen S, Abreu-Goodger C, Piipari M, Redshaw N, Dalmay T, Moreno-Pelayo MA, Enright AJ, Steel KP.
Nature Genetics 41 (5), 614-618 (2009)

Detecting microRNA binding and siRNA off-target effects from expression data.
S van Dongen, C Abreu-Goodger, AJ Enright.
Nature methods 5 (12), 1023-1025 (2008)

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This weeks seminar will be given by our own Prof. Kevin Devine on Friday at 1:00 pm in the Smurfit Atrium.

The title of his seminar will be "Regulation of cell wall metabolism in Bacillus subtilis".

Research in the Devine Lab:

The research focus of the Devine laboratory is the Regulation of Cell Wall Metabolism in Gram Positive bacteria using Bacillus subtilis as a model system.

The cell wall of Gram positive bacteria such as Bacillus subtilis is located exterior to the cytoplasmic membrane and is composed of peptidoglycan and an anionic polymer (often teichoic acid). Together these polymers form a multilayered mesh-type protective sacculus that imparts shape to the cell, resists turgor pressure and is the structure through which the bacterium interacts with its environment. Cell wall integrity is essential for cell viability - agents that disrupt cell wall synthesis or structure, such as eg. the penicillin or vancomycin antibiotics, leads to cell death. Nevertheless, up to 50% of the cell wall polymer is synthesized and turned over during each cell cycle. Thus the cell wall is a highly dynamic structure. Much current research in this area is focused on establishing how cell wall synthesis and turnover are regulated both spatially and temporally and on how this is achieved without compromising cell wall integrity and cell viability.

Their recent work has focused on the bi-location of cell wall metabolic activities - how the production of peptidoglycan and teichoic acid precursors in the cytoplasm is coordinated with cell wall synthesis and turnover within the exterior cell wall. Their work has revealed that the WalRK and PhoPR two-component signal transduction systems, together with a Sigma / anti-sigma factor system (SigI RsgI) play central roles in controlling cell wall metabolism during growth and under stress conditions. Their work is also focused on identifying the molecular signals identified by the WalK and PhoR sensor kinases.

These subjects will be the focus of the seminar.

Some recent papers:

1. Salzberg LI, Powell L, Hokamp K, Botela E, Noone D, Devine KM. (2013). The WalRK (YycFG) and ?(I) RsgI regulators cooperate to control CwlO and LytE expression in exponentially growing and stressed Bacillus subtilis cells.
Mol Microbiol. 87(1):180-95.

2. Bisicchia P, Bui NK, Aldridge C, Vollmer W, Devine KM. (2011). Acquisition of VanB-type vancomycin resistance by Bacillus subtilis: the impact on gene expression, cell wall composition and morphology.
Mol Microbiol. 81(1):157-78.

3. Bisicchia P, Lioliou E, Noone D, Salzberg LI, Botella E, H?bner S, Devine KM. (2010). Peptidoglycan metabolism is controlled by the WalRK (YycFG) and PhoPR two-component systems in phosphate-limited Bacillus subtilis cells.
Mol Microbiol. 75(4):972-89.

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Frank has invited Prof José Luis Riechmann from the Center for Research in Agricultural Genomics (CRAG) in Barcelona, to give a seminar this Friday at 1:00pm in the Smurfit Atrium.

The title of his seminar will be "Genomic Analyses of Gene Regulatory Networks in Plants".

Brief Biography:

José Luis Riechmann is the director of the Center for Research in Agricultural Genomics (CRAG) in Barcelona. He is one of the leading authorities on plant transcription factors and has worked for many years on the characterisation of gene regulatory mechanisms underlying diverse processes during plant development.

His recent papers include:

Huang, W., Pérez-García, P., Pokhilko, A., Millar, A.J., Antoshechkin, I., Riechmann, J.L., Mas, P. (2012) Mapping the core of the Arabidopsis circadian clock defines the network structure of the oscillator. Science 336, 75-79.

Kaufmann, K., Wellmer, F., Muiño, J.M., Ferrier, T., Wuest, S.E., Kumar, V., Serrano-Mislata, A., Madueño, F., Krajewski, P., Meyerowitz, E.M., Angenent, G.C., and Riechmann, J.L. (2010) Orchestration of floral initiation by APETALA1. Science 328, 85-89.

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Adrian has invited Prof Scott Armstrong, director of the Memorial Sloan-Kettering Leukemia Center, to give a seminar this Friday at 1:00pm in the Smurfit Atrium.

The title of his seminar will be "Targeting Histone Methylation in Leukemia Stem Cells"

Scott Armstrong's Research:

The goal of Scott Armstrong's research program is to define genetic and epigenetic programs that control the extensive self-renewal properties associated with leukemia and other cancers. This knowledge is then used to develop rational approaches for potential new therapies. Experiments incorporate the use of sophisticated mouse models of leukemia and the characterization of human leukemia cells.

Prof. Armstrong's lab recently identified leukemia stem cells in a model of human leukemia and demonstrated that acute myelogenous leukemia stem cells express a stem cell program in the context of a more differentiated cell type. This finding has important implications for therapeutic approaches that will target cancer stem cells.

His lab also defined changes in chromosome structure as a critical initial step in leukemia development. These findings have prompted a search for therapies that can reverse this process and eradicate leukemia stem cells. Prof. Armstrong's work is driven by questions that are of immediate clinical relevance and a number of clinical trials have been developed as a direct result of this work.

Selected publications:

Kalaitzidis D, Sykes SM, Wang Z, Punt N, Tang Y, Ragu C, Sinha AU, Lane SW, Souza AL, Clish CB, Anastasiou D, Gilliland DG, Scadden DT, Guertin DA , Armstrong SA. 2012. mTOR complex 1 plays critical roles in hematopoiesis and Pten-loss-evoked leukemogenesis. Cell Stem Cell, (1934-5909), 2012 Sept 07; 11 (3)429.

Heidel FH, Bullinger L, Feng Z, Wang Z, Neff TA, Stein L, Kalaitzidis K, Lane SW, Armstrong SA. Genetic and Pharmacologic Inhibition of β-Catenin Targets Imatinib Resistant Leukemia Stem Cells in CML. Cell Stem Cell, 2012 Apr 6;10(4)412-24.

Neff TA, Sinha AU, Kluk MJ, Zhu N, Khattab M, Stein L, Zie H, Orkin SH, Armstrong SA. Polycomb repressive complex 2 is required for MLL-AF9 leukemia. Proc. Natl. Acad. Sci. 2012 Mar 27;109(13)5028-33.

Onder TT, Kara N, Cherry A, Sinha AU, Zhu N, Bernt KM, Cahan P, Mancarci OB, Unternaehrer J, Gupta PB, Lander ES, Armstrong SA, Daley GQ. Chromatin-modifying enzymes as modulators of reprogramming. Nature. 2012 Mar 4;483(7391):598-602.

Bernt KM, Zhu N, Sinha AU, Vempati S, Faber J, Krivtsov AV, Feng Z, Punt N, Daigle A, Bullinger L, Pollock RM, Richon VM, Kung AL, Armstrong SA. MLL-rearranged Leukemia is Dependent on Aberrant H3K79 Methylation by DOT1L. Cancer Cell 2011, Jul 12;20(1)66-78.

Daigle SR, Olhava EJ, Therkelsen CA, Majer CR, Sneeringer CJ, Song J, Johnson LD, Scott MP, Smith JJ, Xiao Y, Jin L, Kuntz KW, Chesworth R, Moyer MP, Bernt KM, Tsend JC, Kung AL, Armstrong SA, Copeland RA, Richon VM, Pollock RM. Selective Killing of Mixed Lineage Leukemia Cells by a Potent Small-Molecule DOT1L Inhibitor. Cancer Cell 2011, Jul 12;20(1)53-65.

Wang Y, Krivtsov AV, Sinha AU, North TE, Goessling W, Feng Z, Zon LI, Armstrong SA. The Wnt/beta-catenin pathway is required for the development of leukemia stem cells in AML. Science. 2010 Mar 26;327(5973):1650-3.

Krivtsov AV, Feng Z, Lemieux ME, Faber J, Vempati S, Sinha AU, Xia X, Jesneck J, Bracken AP, Silverman LB, Kutok JL, Kung AL, Armstrong SA. H3K79 methylation profiles define murine and human MLL-AF4 leukemias. Cancer Cell. 2008 Nov 4; 15(5):355-68.

Wei G, Twomey D, Lamb J, Agarwal J, Stam R, Opferman JT, Sallan SE, den Boer ML, Pieters R, Golub TR, Armstrong SA. Gene expression-based chemical genomics identifies rapamycin as a modulator of glucocorticoid resistance. Cancer Cell. 2006: 10, 331-42.

Krivtsov AV, Twomey D, Feng Z, Stubbs MC, Wang Y, Faber J, Levine JE, Wang J, Hahn WC, Gilliland DG, Golub TR, Armstrong SA. Transformation from committed progenitor to leukaemia stem cell initiated by MLL AF-9. Nature. 2006: 442, 818-22.

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SPECIAL SEMINAR, 1 pm, Genetics Atrium

Peter Kirwan is a graduate of the Trinity College Genetics department, currently completing his PhD with Rick Livesey at Cambridge, where they are pioneering the derivation of cortical neuronal cell-types from induced pluripotent stem cells from human patients to model cortical development and disease.

Directed differentiation of human pluripotent stem cells to cerebral cortex neurons and neural networks.
Shi Y, Kirwan P, Livesey FJ.
Nat Protoc. 2012 Oct;7(10):1836-46. PubMed

A human stem cell model of early Alzheimer's disease pathology in Down syndrome.
Shi Y, Kirwan P, Smith J, MacLean G, Orkin SH, Livesey FJ.
Sci Transl Med. 2012 Mar 7;4(124):124ra29. PubMed

Human cerebral cortex development from pluripotent stem cells to functional excitatory synapses.
Shi Y, Kirwan P, Smith J, Robinson HP, Livesey FJ.
Nat Neurosci. 2012 Feb 5;15(3):477-86. PubMed

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SPECIAL SEMINAR, 1 pm, Atrium

Shane McCarthy is a genomics researcher studying the genetics of psychiatric and neurodevelopmental disorders. He has helped pioneer the application of whole-genome array and sequencing approaches to identify rare mutations causing schizophrenia, autism and related conditions.

High frequencies of de novo CNVs in bipolar disorder and schizophrenia.
Malhotra D, McCarthy S, et al. Neuron. 2011 Dec 22;72(6):951-63. PubMed

Duplications of the neuropeptide receptor gene VIPR2 confer significant risk for schizophrenia.
Vacic V, McCarthy S, et al. Nature. 2011 Mar 24;471(7339):499-503. PubMed

High frequencies of de novo CNVs in bipolar disorder and schizophrenia.
Malhotra D, McCarthy S, et al Neuron. 2011 Dec 22;72(6):951-63. PubMed

Rare structural variants in schizophrenia: one disorder, multiple mutations; one mutation, multiple disorders.
Sebat J, Levy DL, McCarthy SE. Trends Genet. 2009 Dec;25(12):528-35. PubMed

Microduplications of 16p11.2 are associated with schizophrenia.
McCarthy SE, et al. Nat Genet. 2009 Nov;41(11):1223-7. PubMed

Rare structural variants disrupt multiple genes in neurodevelopmental pathways in schizophrenia.
Walsh T, McClellan JM, McCarthy SE, et al. Science. 2008 Apr 25;320(5875):539-43. PubMed

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Adrian has invited Dr John Stingl from the Department of Oncology, University of Cambridge to give a seminar this Friday at 1:00pm in the Smurfit Atrium.

The title of his seminar will be "Mammary stem and progenitor cells: Understanding the cellular context of breast cancer"

Brief Biography:

The research of Dr John Stingl focuses on identifying stem and progenitor cells in both the human and mouse mammary glands. He is interested in these cells because cancer theory suggests that it is these cells that are the initial targets for malignant transformation in breast cancer. He is also interested in understanding the influence of common breast cancer-associated mutations on normal breast stem and progenitor cell function and identifying the cell of origin of different types of breast tumours.

Key publications:

Enzymatic dissociation, flow cytometric analysis, and culture of normal mouse mammary tissue.
Prater M, Shehata M, Watson CJ, Stingl J.
Methods Mol Biol. 2013;946:395-409. doi: 10.1007/978-1-62703-128-8_25.

TGFbeta induces the formation of tumour-initiating cells in claudinlow breast cancer.
Bruna A, Greenwood W, Le Quesne J, Teschendorff A, Miranda-Saavedra D, Rueda OM, Sandoval JL, Vidakovic AT, Saadi A, Pharoah P, Stingl J, Caldas C.
Nat Commun. 2012;3:1055. doi: 10.1038/ncomms2039.

Quantitation of human mammary epithelial stem cells with in vivo regenerative properties using a subrenal capsule xenotransplantation assay.
Eirew P, Stingl J, Eaves CJ.
Nat Protoc. 2010 Dec;5(12):1945-56. doi: 10.1038/nprot.2010.148.

A method for quantifying normal human mammary epithelial stem cells with in vivo regenerative ability.
Eirew P, Stingl J, Raouf A, Turashvili G, Aparicio S, Emerman JT, Eaves CJ.
Nat Med. 2008 Dec;14(12):1384-9. doi: 10.1038/nm.1791. Epub 2008 Nov 23.

Molecular heterogeneity of breast carcinomas and the cancer stem cell hypothesis.
Stingl J, Caldas C.
Nat Rev Cancer. 2007 Oct;7(10):791-9. Review.

Purification and unique properties of mammary epithelial stem cells.
Stingl J, Eirew P, Ricketson I, Shackleton M, Vaillant F, Choi D, Li HI, Eaves CJ.
Nature. 2006 Feb 23;439(7079):993-7. Epub 2006 Jan 4.