Pombo Lab
Epigenetic Regulation and Chromatin Architecture
Profile
We study mechanisms of gene expression at multiple levels, from the local action of transcription factors, to long-range chromatin looping events that connect regulatory DNA sequences with the genes they regulate, to how whole chromosomes are positioned within cell nuclei. Binding of transcription factors at regulatory sequences helps recruit chromatin remodelers and the transcription machinery to transcription sites.
Upon recruitment, RNA polymerases either remain primed for subsequent activation (e.g. after environmental stress, during differentiation or disease), or directly transcribe the DNA template into RNA molecules, which code for proteins or for structural RNAs that constitute many enzymatic complexes.
An increasingly important aspect of gene regulation is the three-dimensional folding of the genome, and the mechanisms that control physical contacts of distant regulatory DNA sequences with gene promoters to activate gene expression. To directly measure genome topologies, our group developed Genome Architecture Mapping (GAM).
Our long-term strategy for unravelling the principles of genome function in higher eukaryotes aims to integrate multiple parameters, which is becoming increasingly possible with state-of-the-art developments in single cell genomics, molecular biology, epigenetics, nuclear imaging, and genetics.
Team
Alumni
year | name and position | current position |
---|---|---|
2022 - 2023 |
Lilith Klaus BSc student |
|
2022 |
Julia Markowski Postdoc |
Postdoctoral fellow, Blavatnik Institute of Biomedical Informatics, Harvard Medical School, Boston, US (with Peter Park) |
2022 |
Mattia Conte Postdoc |
Postdoctoral fellow (Nicodemi lab), Naples University, Naples, IT |
2022 |
Federico Billeci MSc student |
Data Scientist, Integra Therapeutics, SP |
2022 |
Berta Jimenez-Alfaro Hacha MSc student |
Pombo lab, MDC, DE |
2019 - 2022 |
Jennifer A. Giannini PhD student (Fullbright Scholar 2019) |
Scientific content creator, Labforward, Berlin, DE |
2021 |
Simona Bianco Postdoc |
Assistant Professor, Naples University, Naples, IT |
2021 |
Chloe Tang MSc student |
PhD student, Rippe lab, DKFZ, Heidelberg, DE |
2020 - 2021 |
Lavanya Iyer Postdoc |
Task Force Lead, Single-cell Omics, Evotec, Göttingen, DE |
2019 - 2020 |
Cleis Battaglia MSc student |
PhD student, Marenduzzo lab, Univ. Edinburgh, UK |
2021 |
Rita Moldovan BSc student |
|
2017 - 2021 |
Ehsan Irani Postdoc |
Senior Data Scientist, IntelliSense.io |
2015 - 2021 |
Gesa Loof PhD student / Postdoc |
Postdoctoral fellow, Inst. Biology Development, Marseille, FR (with Thomas Lecuit) |
2014 - 2020 |
Ana Miguel Fernandes PhD student / Postdoc |
Data scientist, OLX Group, Berlin, DE |
2014 - 2020 |
Rieke Kempfer PhD student / Postdoc |
NGS specialist, SOPHiA Genetics, Geneva, Switzerland |
2018 |
David Pride MSc student |
Medical Trainee, Texas Tech School of Medicine, El Paso, US |
2018 |
Vahid Assimi MSc student |
PhD student, Hinsz lab, MPI Molecular Genetics, Berlin, DE |
2015 - 2018 |
Konstantina Skourti-Stathaki Postdoc |
Principal Scientist, RNA Biology, MiNA Therapeutics, London, UK |
2012 - 2018 |
Elena Torlia Triglia PhD student /Postdoc |
Postdoctoral fellow, Broad Institute, Boston, US (with Brad Bernstein) |
2014 - 2018 |
Giulia Caglio PhD student |
Full Stack Data Scientist, Consultant, Catenion, Berlin, DE |
2014 - 2018 |
Marta Slimak-Mastrobuoni Postdoc |
Commercial Development Manager Europe, Sterilex, Berlin, DE |
2013 - 2018 |
Dorothee Krämer PhD student |
Global Medical Grant Developer, Medscape, Grenoble, FR |
2017 |
Franka Rang MSc student |
PhD student, Kind lab, Hubrecht Institute, Utrecht, NL |
2017 |
Daria Ivanove BSc student |
|
2013 - 2017 |
Tiago Rito Postdoc |
Postdoctoral fellow, Crick Institute, London, UK (with James Briscoe) |
2010 - 2017 |
Joao Dias PhD student / Postdoc |
Postdoctoral Fellow, Montpellier, FR (with Monsef Benkirane) |
2008 - 2017 |
Carmelo Ferrai Postdoc |
Postdoctoral Fellow, Göttingen, DE (with Philipp Stroebel) |
2016 |
Leonid Serebreni MSc student |
Postdoctoral Fellow, Junker lab, MDC, Berlin, DE |
2016 |
A. Julieta Ramirez Cuellar MSc student |
Business co-founder, Guanajuato, Mexico |
2013 - 2016 |
Markus Schüler Postdoc |
Head of Data Strategy, mobile.de/eBay, Berlin, DE |
2013 - 2016 |
Mariano Barbieri Postdoc |
Postdoctoral Fellow, Göttingen, DE (with Argyris Papantonis) |
2011 - 2016 |
Robert A. Beagrie PhD student / Postdoc |
Group Leader, Sir Henry Dale fellow, Wellcome Trust Centre, Oxford, UK |
2008 - 2014 |
Kelly J. Morris PhD student / Postdoc |
Career break |
2015 |
Marisa Saponaro MSc student |
Clinical Research Associate, Syneos Health Clinical Solutions, Rome, IT |
2009 - 2013 |
Kedar Natarajan PhD student / Postdoc |
Associate Professor, University of Southern Denmark, Odense, Denmark |
2000 - 2013 |
Sheila Q. Xie Postdoc |
Senior Postdoctoral Fellow, MRC-LMS, UK (with Michelle Percharde) |
2008 - 2013 |
Liron-Mark Lavitas PhD student / Postdoc |
Clinical Project Assistant, PPD Pharmaceuticals, Munich, DE |
2007 - 2013 |
Inês de Castro PhD student / Postdoc |
Lecturer, Brunel University London, UK |
2011 - 2013 |
C. Ribeiro de Almeida Postdoc |
Group Leader, Babraham Institute, Cambridge, UK |
2008 - 2012 |
Mita Pabari Postdoc |
Medical Writer, MIMS (Hong Kong) Limited |
2007 - 2012 |
Inês de Santiago PhD student / Postdoc |
Senior Principal Scientist – Computational Biology, e-Therapeutics PLC, Oxford, UK |
2007 - 2011 |
Emily Brookes PhD student / Postdoc |
Lecturer in Biomedical Research & Group Leader, University of Southampton, UK |
2004 - 2010 |
Andre Möller Postdoc |
Assistant Editor, BMC Biology, BioMed Central |
2009 |
Patrizia Beolchi MSc student |
Clinical Trial Manager, Medpace, London, UK |
2008 |
Kelly J Morris MRes student |
|
2003 - 2008 |
Miguel R. Branco PhD student / Postdoc |
Reader, Queen Mary University London, Blizard Institute, London UK |
2007 |
Liron Mark Lavitas MRes student |
|
2007 |
Pippa Hadland (neé Clarke) MRes student |
|
2007 |
Jonathan Pavelin MRes student |
|
2003 - 2007 |
Julie K. Stock PhD student / Postdoc |
Biotech and Pharma Consultant, Freelance and Blue Hearth Diagnostics, UK |
2006 |
Emily Brookes MRes student |
|
2006 |
Nikolay Popov MRes student |
|
2005 |
Claire Mitchell MRes student |
|
2005 |
Edward Andres MRes student |
|
2001 - 2004 |
Pascale V. Guillot Postdoc |
Professor of Stem Cell and Gene Therapy, UCL Great Ormond Street Institute of Child Health, London, UK |
2000 - 2004 |
Sonya Martin PhD student |
Microscopy Support Officer, Microscopy Academic Units, University of Southampton, Southampton, UK |
2003 |
Julie K. Stock MRes student |
|
2002 |
James Dixon MRes student |
Research
Our main goal is to unravel the diverse mechanisms of mammalian gene regulation and their roles in development and disease. Gene activation is controlled locally through transcription factors, chromatin modifiers, and the transcription and RNA processing machineries. Gene expression is also intricately regulated by the three-dimensional (3D) structure of the genome, which modifies the location of genes relative to activating or repressing biochemical environments. Repressing nuclear locations include the nuclear lamina and heterochromatin. Activating 3D genome conformations can work by regulating the physical proximity between regulatory regions and their responsive genes. As many disease-associated genetic variants fall in non-coding regulatory elements scattered in the genome, our work aims to advance the functional interpretation of the linear genome sequence. We especially put effort in devising experimental and computational approaches to map 3D genome structure in different cell types, in development and in disease, to study developmental and disease mechanisms, towards novel diagnostics, prognostics and therapeutics.
We have developed Genome Architecture Mapping (GAM), an orthogonal 3D genome folding mapping technology which yields fine maps of chromatin contacts from small cell numbers (500-1000), and is uniquely powerful to quantify different metrics of 3D genome structure, such as multiway contacts and chromatin melting. With immuno-GAM, we introduced the selection of cell types within complex tissues to enable the application of GAM in rare cells, such as dopaminergic neurons in the midbrain. GAM is an inherently suited platform for multimodal molecular phenotyping of biological samples, from genome sequence and 3D structure, to transcript and protein quantification. As a first step towards GAM multimodality, we have developed Oligo-Seq, a novel approach to detect minute amounts of specific RNA sequences within thin tissue cryosections, as used for GAM. We currently develop the application of Oligo-seq in spatial transcriptomics, especially in archival clinical samples (e.g. FFPE). By further developing multimodal integration of 3D genome topology, with the abundance of specific regulatory factors and gene expression, at the single-cell level, we aim to extract dynamic states of gene regulation and cause-effect relationships that connect 3D genome structure with gene expression. Ultimately, we seek to advance the interpretability of the linear genome sequence, to gain a deeper understanding of 3D genome regulation mechanisms in gene expression, and to advance their predictability.
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