Our research group focuses on understanding the fundamental principles that govern how the three-dimensional architecture of the human genome is established and maintained. To this end, we apply single-molecule DNA and RNA fluorescence in situ hybridization (FISH) techniques to visualize the position and structure of DNA loci and chromosomes, together with the expression of selected genes, at high resolution in thousands of individual cells. In parallel, we develop new methods based on next-generation sequencing, that allow us to measure the radial position of DNA loci genome-wide. We combine state-of-the-art cell culture techniques with genetic and chemical manipulation of genome structure and function, and then apply our methods to probe for structural and functional changes that occur genome-wide or at selected loci.
In the past four years, we have established a powerful platform—iFISH—that enables us to produce hundreds of oligonucleotide probes for DNA and RNA FISH at affordable cost, in a short time. We are now using iFISH to label all human chromosomes with DNA FISH probes evenly spaced every one megabase (Mb), and then build an atlas of chromosome structures and arrangements in different cell types and tissues. In parallel, we have developed a method for Genomic loci Positioning by Sequencing—GPSeq—that allows us to measure, genome-wide, the radial position that a DNA locus occupies in the nucleus, with respect to the nuclear periphery/center. We are now applying GPSeq to find out whether different cell types harbor different radial genome configurations, as well as to learn how chromosomal territories form and arrange themselves in the nucleus, at the end of each mitosis.
Magda Bienko, PhD, Principal Investigator
Silvano Garnerone, senior scientist
Lei Xu, senior scientist
Federico Agostini, postdoc
Joaquin Custodio, postdoc
Erik Wernersson, postdoc
Eleni Gelali, PhD student
Gabriele Girelli, PhD student
Tomasz Kallas, PhD student
Ana Mota, PhD student
CUTseq enables integrated imaging and multi-region sequencing of individual tissue sections
Xiaolu Zhang, Silvano Garnerone, Marcin Nicoś, Caterina Marchio, Michele Simonetti, Tiziana Venesio, Anna Sapino, Johan Hartman, Magda Bienko*, Nicola Crosetto*
in review for Nature Communications
iFISH is a free resource for large-scale parallelized design and production of DNA FISH probes
Eleni Gelali, Xinge Li, Gabriele Girelli, Masahiro Matsumoto, Erik Wernersson, Joaquin Custodio, Ana Mota, Maud Schweitzer, Katalin Ferenc, John P. Schell, Fredrik Lanner, Nicola Crosetto*, Magda Bienko*
in revision for Nature Communications
RollFISH achieves robust quantification of single-molecule RNA biomarkers in paraffin-embedded tumor tissue samples.
Wu C, Simonetti M, Rossell C, Mignardi M, Mirzazadeh R, Annaratone L, Marchiò C, Sapino A, Bienko M, Crosetto N, Nilsson M.
Commun Biol. 2018 Nov 28
An Application-Directed, Versatile DNA FISH Platform for Research and Diagnostics.
Gelali E, Custodio J, Girelli G, Wernersson E, Crosetto N, Bienko M.
Methods Mol Biol. 2018
Genome-Wide Profiling of DNA Double-Strand Breaks by the BLESS and BLISS Methods.
Mirzazadeh R, Kallas T, Bienko M, Crosetto N.
Methods Mol Biol. 2018
BLISS is a versatile and quantitative method for genome-wide profiling of DNA double-strand breaks.
Yan WX, Mirzazadeh R, Garnerone S, Scott D, Schneider MW, Kallas T, Custodio J, Wernersson E, Li Y, Gao L, Federova Y, Zetsche B, Zhang F, Bienko M, Crosetto N.
Nat Commun. 2017 May 12
Quantification of HER2 and estrogen receptor heterogeneity in breast cancer by single-molecule RNA fluorescence in situ hybridization.
Annaratone L, Simonetti M, Wernersson E, Marchiò C, Garnerone S, Scalzo MS, Bienko M, Chiarle R, Sapino A, Crosetto N.
Oncotarget. 2017 Mar 21
Massive and parallel expression profiling using microarrayed single-cell sequencing.
Vickovic S, Ståhl PL, Salmén F, Giatrellis S, Westholm JO, Mollbrink A, Navarro JF, Custodio J, Bienko M, Sutton LA, Rosenquist R, Frisén J, Lundeberg J.
Nat Commun. 2016 Oct 14
Genome-wide maps of nuclear lamina interactions in single human cells.
Kind J, Pagie L, de Vries SS, Nahidiazar L, Dey SS, Bienko M, Zhan Y, Lajoie B, de Graaf CA, Amendola M, Fudenberg G, Imakaev M, Mirny LA, Jalink K, Dekker J, van Oudenaarden A, van Steensel B.
Cell. 2015 Sep 24
We are always interested in recruiting talented and curious people, with a strong passion for science, in general, and genome biology, in particular. We very much welcome applications from people who have a keen interest in microscopy techniques and are interested in applying our FISH methods to visualize fascinating aspects of genome architecture and function in single cells.