Spatial Genome Architecture in Development & Disease
The Programme
Programme Description
Eukaryotic genomes encode the information that defines both general and specific characteristics of each cell type. However, the linear DNA sequence alone often fails to predict cellular functions and phenotypic outcomes. In fact, genomic information is modified and regulated by a number of additional layers of gene expression control. One of these, the spatial folding of chromosomes, has been recently identified as a critical such layer. Spatial chromosomal folding is established through binding of transcription factors as well as via epigenetic mechanisms and biophysical forces that act in a concerted manner to regulate gene expression in space and time. Therefore, studying the principles of three-dimensional chromatin folding allow us to unravel its contribution in gene regulation during development and disease. This Priority Program, SPP2202, began its work in 2019 and has brought together >30 Principal and Affiliated Investigators from different sites across Germany to promote this emerging research area.
Major Aims
In our effort to further the emerging field of spatial genome organization, SPP2202 researchers work to meet the following major aims:
- To develop and apply novel technologies that can capture spatial chromatin conformation, also in conjunction with other genomic features (e.g., transcription, histone modifications, DNA methylation), to resolve and track features of genomic architecture in the nucleus down to the single cell-level
- to functionally dissect the impact of 3D chromatin folding on gene expression using in vitro and in vivo model systems or human samples during cell differentiation
- To causally connect 3D chromatin folding with disease pathology by integrating precision genome editing and patient data and/or disease models
- To develop and apply novel computational approaches that will allow us to integrate, visualise, and quantitatively model the end-effects and dynamics of spatial genome organisation
By focusing on chromatin folding and gene regulation, the SPP2202 consortium addresses a field of biomedicine that goes beyond the study of genes and their function in order to fully understand their regulation. Building on one of the most important discoveries in Genomics of the past decade, we take the next step in investigating how chromatin folding governs differentiation, development, and disease, thereby addressing a pertinent question in Life Sciences: how cellular individuality is achieved at a genomic level. Once deciphered, these rules will allow us to predict how different cell types respond to signaling cues upon development or disease manifestation.
Funded since 2019
Program Committee
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Papantonis, Argyris
Göttingen -
Furlong, Eileen
Heidelberg -
Pombo, Ana
Berlin -
Mundlos, Stefan
Berlin
-
Dr. Jan Ellenberg,
Heidelberg -
Dr. Eileen E. M. Furlong,
Heidelberg -
Dr. Claudia Gebhard,
Regensburg -
Dr. Edith Heard,
Heidelberg -
Dr. Eugene Kim,
Frankfurt -
Dr. A. Marieke Oudelaar,
Göttingen -
Dr. Argyris Papantonis,
Göttingen -
Dr. Anna Poetsch,
Dresden -
Dr. Tomohisa Toda,
Erlangen -
Dr. Ana Pombo,
Berlin -
Dr. Karsten Rippe,
Heidelberg -
Dr. Edda Schulz,
Berlin -
Dr. Roland Schwarz,
Cologne -
Dr. Daphne Selvaggia Cabianca,
Munich -
Dr. Malte Spielmann,
Lübeck -
Dr. Maria Elena Torres-Padilla,
Munich -
Dr. Frank Westermann,
Heidelberg -
Dr. Carl Herrmann,
Heidelberg
Visualising nanoscale 3D genome architecture and transcriptional state during cell fate specification in the early mouse embryo
Assessing the functional role of cohesin and transcription in genome topology during Drosophila embryogenesis
Understanding how changes in spatial chromatin organization cause defective gene expression in acute myeloid leukemia with STAG2 mutations
Activity-dependent gene expression in male and female neurons: 3D genome architecture, transcription and chromatin mechanisms
Understanding the interplay between transcription and cohesin-mediated loop extrusion at the single molecule level
Dissecting structural and functional cooperation between cis-regulatory elements in higher-order chromatin structures
Exploring the contribution of RNA polymerases to mammalian 3D genome architecture
Nuclear pore complex proteins-directed 3D nuclear architecture in neural development and disease
Deregulation of 3D genome structure in models of memory and learning disability
Functional organization of co-regulated RNA polymerase II nuclear subcompartments activated by TNFα or TGFβ
Architectural Rearrangements at the Xist locus during the onset of X-chromosome inactivation
Algorithms for inferring haplotype-specific chromatin contact maps in cancer using Genome Architecture Mapping
Revealing the function of heterochromatin spatial organization in response to early-life environmental challenges in C. elegans
Position effects in the 3D genome as the cause of neurodevelopmental disorders
Coordination and function of nuclear lamina and nuclear pore compartmentalisation in genome organisation during early mouse development
Modeling embryonal neuroblastoma tumorigenesis by activation of chromosomal 3D super enhancer interactions and genomic instability
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Dr. Boyan Bonev,
Munich -
Dr. Magdalena Götz,
Munich -
Dr. Nicolas Casadei,
Tübingen -
Dr. Fubo Cheng,
Tübingen -
Dr. Sarah Doerdrechter-Kinkley,
Berlin -
Dr. Carmelo Ferrai,
Göttingen -
Dr. Christof Gebhardt,
Ulm -
Dr. Martin Kircher,
Lübeck -
Dr. Scott Lacadie,
Berlin -
Dr. Didier Y. Stainier,
Bad Nauheim -
Dr. Darío Jesús Lupiáñez García,
Berlin -
Dr. Robert Patrick Zinzen,
Berlin -
Dr. Marina Lusic,
Heidelberg -
Dr. Stefan Mundlos,
Berlin -
Dr. Vassilis Roukos,
Mainz -
Dr. Michela Virgilio,
Berlin -
Dr. Tanja Vogel,
Freiburg