SFB 992:  Medical Epigenetics (MEDEP) - From Basic Mechanisms to Clinical Applications

• Subject Area: Medicine ; Biology
• Term: from 2012 to 2024
• Website: Homepage
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 192904750

Modern bioscience has entered a post-genomic era that is highlighted by seminal discoveries in the area of epigenetics. Normal development, cell type identities and disease require a better understanding of chromatin and of epigenetic control. The DNA sequence alone is not sufficient to explain all aspects of heritable physiology and pathology and the recent breakthroughs in epigenetic research have revolutionised insights into normal and perturbed development. In addition, technological advances now allow the genome-wide mapping of epigenetic signatures, such as DNA methylation profiles or histone modification marks. Furthermore, new approaches to combat pathological dysfunction through small molecule inhibitors of chromatin modifying enzymes have become a reality. Therefore, a better diagnosis and treatment of human disease necessitates the translation of epigenetic control mechanisms and genome-wide chromatin profiles to clinical applications.The CRC 992 “Medical Epigenetics”, MEDEP, provides such a translational program for epigenetic research. Scientists from the University Freiburg Medical Center, the University of Freiburg and the Max Planck Institute of Immunobiology and Epigenetics team up in a consortium that addresses questions ranging from the identification of basic epigenetic principles, validation of epigenetic pathways in relevant animal models of human disease to the translation of epigenetic principles to clinical applications. Core infrastructures provide deep-sequencing/bioinformatics capacity for the generation and analysis of epigenetic profiles and a platform for rational drug design of small molecule inhibitors of epigenetic targets. A major asset of MEDEP is the complementary and interdisciplinary approach to bridge between basic and clinical research and to build a network of exchange, collaborations, and mentoring of young scientists.

• DFG Programme: Collaborative Research Centres

Current projects

• A01 - The basic composition of mammalian heterochromatin (Project Head Jenuwein, Thomas )
• A02 - The role of histone acetyltransferase MOF in development and disease (Project Head Akhtar, Ph.D., Asifa )
• A04 - Chemical Epigenetics – Inhibitors of histone methyltransferases (Project Head Jung, Manfred )
• A07 - Epigenetic regulation of TFIID recruitment and activity (Project Head Timmers, Marc )
• A08 - Regulation of chromatin accessibility by Tbx factors guiding embryonic cell lineage specification (Project Head Arnold, Sebastian J. )
• B01 - Characterisation of the lysine methyltransferases KMT9 and KMT10 (Project Head Schüle, Roland )
• B02 - Epigenetic effects of NFE2 and JAK2V617F mutations in MPN (Project Head Pahl, Heike L. )
• B03 - Epigenetic mechanisms in cardiac failure and recovery (Project Head Hein, Lutz )
• B06 - Establishment of chromatin states in the early embryo (Project Head Iovino, Ph.D., Nicola )
• B07 - Epigenetic targeting of dormant leukemic stem cells (Project Head Cabezas-Wallscheid, Nina )
• C02 - Lysine-specific demethylases as modulators of CNS glia cell function and neurodegeneration (Project Head Prinz, Marco )
• C04 - Epigenetic agent treatment through reactivation of repressed, haploinsufficient tumour suppressor genes in high-risk AML (Project Head Lübbert, Ph.D., Michael )
• C05 - Targeting disease-causing cells by DNA hypomethylation in juvenile myelomonocytic leukaemia (Project Head Flotho, Christian )
• C07 - Epigenome-wide Association Studies of Kidney Function and Chronic Kidney Disease (Project Head Köttgen, Anna )
• MGK - Integrated Research and Training Group (IRTG) (Project Head Jung, Manfred )
• Z01 - Deep-Sequencing / Bioinformatics (Project Heads Backofen, Rolf ;  Manke, Thomas )
• Z02 - Epigenetische Wirkstoffentwicklung: Molekül Identifizierung und Optimierung, sowie Target Validierung (Project Heads Breit, Bernhard ;  Einsle, Oliver ;  Günther, Stefan )
• Z03 - Central Tasks of the Collaborative Research Centre (Project Head Schüle, Roland )

Completed projects

• A03 - Implication of histone H3K79 methylation in cerebellar development and dysfunction (Project Head Vogel, Tanja )
• A05 - Stochastic epigenetic control of obesity by Trim28 (Project Head Pospisilik, Ph.D., John Andrew )
• A06 - Targeting the stability of chromatin factors driving leukaemia (Project Head Sawarkar, Ph.D., Ritwick )
• B04 - Attenuation of an immune evasion strategy of tumours by histone deacetylase inhibitors (Project Head Diefenbach, Andreas )
• B05 - Epigenetic programming of kidney development (Project Head Huber, Tobias B. )
• C03 - Epigenetic regulation of esophageal cancer (Project Head Laßmann, Silke )
• C06 - Epigenetics and therapeutic options of EMT-associated drug resistance in pancreatic cancer (Project Heads Brabletz, Thomas ;  Keck, Tobias )

• Applicant Institution: Albert-Ludwigs-Universität Freiburg
• Participating Institution: Max-Planck-Institut für Immunbiologie und Epigenetik
• Spokesperson: Professor Dr. Roland Schüle