DNA repair; Nuclear envelope; Yeast; Superresolution microscopy; Chemistry; single molecule localization; Bicyclic compounds; Telomeres; C elegans
MarcominiIsabella, ShimadaKenji, DelgoshaieNeda, Yamamoto Io, SeeberAndrew, Cheblalanais, HorigomeChihiro, NaumannUlrike, GasserSusan (2018), Asymmetric Processing of DNA Ends at a Double-Strand Break Leads to Unconstrained Dynamics and Ectopic Translocation, in Cell Reports
, 24 (10), 2614-2628.
Harr JC, Gonzalez-Sandoval A, Gasser SM (2016), Histones and histone modifications in perinuclear chromatin anchoring: from yeast to man, in EMBO Report
, 2, 139-155.
Horigiome C, Bustard DE, Marcomini I, Delgoshaie N, Tsai-Pflugfelder M, Cobb JA, Gasser SM (2016), PolySUMOylation by Siz2 and Mms21 triggers relocation of DNA breaks to nuclear pores through the Slx5/Slx8 STUbL, in Genes Develpment
, 30(8), 931-945.
Gonzalez-Sandoval A, Gasser SM (2016), Spatial Control Over Gene Expression, in Trends Genetic
, June 13, 1.
Platonova E, Winterflood CM, Ewers H (2015), A simple method for GFP- and RFP-based dual color single-molecule localization microscopy, in ACS Chem Biol
, 10(6), 1411-1416.
Kaplan C, Jing B, Winterflood CM, Bridges AA, Occhipinti P, Schmid J, Grinhagens S, Gronemeyer T, Tinnefeld P, Ewers H (2015), Absolute Arrangement of Subunits in Cytoskeletal Septin Filaments in Cells Measured by Fluorescence Microscopy, in Nano Lett
, 15(6), 3859-3854.
Winterflood CM, Platonova E, Albrecht D, Ewers H (2015), Dual-color 3D superresolution microscopy by combined spectral-demixing and biplane imaging, in Biophys J
, 109(1), 3-6.
Marcomini I, Gasser SM (2015), Nuclear organization in DNA end processing: Telomeres vs double-strand breaks, in DNA Repair (Amst)
, 32, 134-140.
Kaplan C, Ewers H (2015), Optimized sample preparation for single-molecule localization-based superresolution microscopy in yeast, in Nat Protoc
, 10(7), 1007-1021.
Gonzalez-Sandoval A, Towbin BD, Kalck V, Cabianca DS, Gaidatzis D, Hauer MH, Geng L, Wang L, Yang T, Gasser SM (2015), Perinuclear Anchoring of H3K9-Methylated Chromatin Stabilizes Induced Cell Fate in C. elegans Embryos, in Cell
, 163(6), 1333-1347.
Su XA, Dion V, Gasser SM, Freundenreich CH (2015), Regulation of recombination atyeast nuclear pores controls repair and triplet repeat stability, in Genes Development
, 29(10), 1006-1017.
Mikhaylova M, Cloin BM, Finan K, van den Berg R, Teeuw J, Kijanka MM, Sokolowski M, Katrukha EA, Miadorn M, Kapitein LC (2015), Resolving bundled microtubules using anti-tubulin nanobodies, in Nat Commun
, 6, 7933.
Platonova E, Winterflood CM, Junemann A, Albrecht D, Faix J, Ewers H (2015), Single-molecule microscopy of molecules tagged with GFP or RFP derivatives in mammalian cells using nanobody binders, in Methods
, 88, 89-97.
Horigome C, Dion V, Seeber A, Gehlen LR, Gasser SM (2015), Visualizing the spatiotemporal dynamics of DNA damage in budding yeast, in Methods Mol Biol.
, 1292, 77-96.
Heinis C (2014), Drug discovery: Tools and rules for macrocycles, in Nat Chem Biol
, Jul 20, 1.
Chen S, Bertoldo D, Angelini A, Pojer F, Heinis C (2014), Peptide ligands stabilized by small molecules, in Angew Chem Int Ed Engl.
, 53(6), 1602-1606.
Bellotto S, Chen S, Rebollo I, Wegner HA, Heinis C (2014), Phage selection of photoswitchable peptide ligands, in J Am Chem Soc
, 136(16), 5880-5883.
Winterflood CM, Ewers H (2014), Single-molecule localization microscopy using mCherry, in Chemphyschem
, 15(16), 3447-3451.
Chen S, Touati J, Heinis C (2014), Tracking chemical reactions on the surface of filamentous phage using mass spectrometry, in Chem Commun (Camb)
, 50(40), 5267-5269.
Rohner S, Kalck V, Wang X, Ikegami K, Lieb JD, Gasser SM, Meister P (2013), Promoter- and RNA polymerase II-dependent hsp-16 gene association with nuclear pores in Caenorhabditis elegans, in J. Cell Biol.
, 200(5), 589-604.
Dion V. and Gasser S.M. (2013), Chromatin movement in the maintenance of genome stability, in Cell
, 152, 1255 -1364.
Chen S, Gfeller D, Buth SA, Michielin O, Leiman PG, Heinis C (2013), Improving binding affinity and stability of peptide ligands by substituting glycines with D-amino acids, in Chembiochem
, 14(11), 1316-1322.
Ries J, Udayar V, Soragni A, Hornemann S, Nilsson KP, Riek R, Hock C, Ewers H, Aguzzi AA, Rajendran L (2013), Superresolution imaging of amyloid fibrils with binding-activated probes, in ACS Chem Neurosci
, 4(7), 1057-1061.
Kleine Borgmann LA, Ries J, Ewers H, Ulbrich MH, Graumann PL (2013), The bacterial SMC complex displays two distinct modes of interaction with the chromosome, in Cell Rep
, 3(5), 1483-1492.
Ferreira HC, Towbin BD, Jegou T, Gasser SM (2013), The shelterin protein POT-1 anchors Caenorhabditis elegans telomeres through SUN-1 at the nuclear periphery, in J. Cell. Biol
, 203(5), 727-735.
Ferreira Helder C, Towbin Benjamin D, Jegou Thibaud, Gasser Susan M (2013), The shelterin protein POT-1 anchors Caenorhabditis elegans telomeres through SUN-1 at the nuclear periphery., in The Journal of cell biology
, 203(5), 727-35.
Cabianca DS, Gasser SM, Spatial segregation of heterochromatin: uncovering functionality in a multicellular organism, in Nucleus
, May 17, 1.
Horigome Chihiro, Oma Yukako, Konishi Tatsunori, Schmid Roger, Marcomini Isabella, Hauer Michael H, Dion Vincent, Harata Masahiko, Gasser Susan M, Swr1 and INO80 Chromatin Remodelers Contribute to DNA Double-Strand Break Perinuclear Anchorage Site Choice., in Molecular cell
Spatial analysis of proteins involved in the processing and repair of chromosome ends by super-resolution microscopy, exploiting bicyclic peptidic binders in high resolution imagingThe organization of chromatin in the nucleus is one of the most basic processes that defines eukaryotic life, and the nuclear envelope is the major structural scaffold for its functional organization. The nuclear envelope is clearly compartmentalized, most molecular players remain to be identified and the exact organization is obscured by the resolution limit of light microscopy. Even present superresolution microscopy methods cannot resolve chromatin attachment points or provide the throughput required to determine, where dozens of proteins are localized in the inner nuclear membrane. We have assembled a team of three research groups with complementary expertise for a focused project on the nanoscale organization of the eukaryotic nuclear envelope. The Gasser group is a leader in 3D organization of chromatin in the nucleus. The Ewers group has developed a novel approach for high-throughput single molecule superresolution microscopy in yeast at unprecedented resolution. The Heinis group has developed a novel method to generate small molecule 'peptidic binders' against any desired protein target.We will combine these novel technologies with the aim of -1. identifying novel nuclear envelope proteins by proteomic studies on yeast and C elegans by the Gasser lab-2. we will then use this data to generate a nanoscale map of all nuclear envelope molecules by high-throughput superresolution microscopy in the Ewers laboratory.-3. we will then develop bicyclic peptidic binders against specific molecules from the above studies, and use these to study the specific localization of telomeres and DNA-double-strand breaks in relation to prominent nuclear features such as nuclear pores in response to DNA-damage.The results of this project will be: a) the generation of a novel labeling method for superresolution microscopy that through combination of organic dyes with small molecule labeling will have unprecedented resolution. b) fundamental insight into the organization of chromatin at the nuclear envelope with enormous breadth and depth of data. c) the identification of novel mechanisms in the specific localization of telomeres and DNA-double-strand breaks.Our work will generate technological leadership in a key technology, provide insight into a fundamental biological system and may yield novel targets for the therapy of human disease.