EXC 81:  Zelluläre Netzwerke: Von der Analyse molekularer Mechanismen zum quantitativen Verständnis komplexer Funktionen

• Fachliche Zuordnung: Grundlagen der Biologie und Medizin ; Mikrobiologie, Virologie und Immunologie ; Neurowissenschaften
• Förderung: Förderung von 2006 bis 2019
• Webseite: Zur Homepage
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 24122740

• Erstellungsjahr: 2019

Zusammenfassung der Projektergebnisse

Die Heidelberger Lebenswissenschaften zeichnen sich durch eine außergewöhnliche Dichte international renommierter Institutionen in engster Nachbarschaft aus. Heidelberg hat eine für Deutschland einzigartige kritische Masse an wissenschaftlicher und technologischer Expertise, und ist daher ein idealer Standort für ein interdisziplinäres Center mit der Zielsetzung, die Struktur, Funktion und Evolution subzellulärer und suprazellulärer Netzwerke zu verstehen. CellNetworks, gegründet in 2006, vereinigt eine große Zahl ausgewiesener Gruppen aller Heidelberger biowissenschaftlicher Institutionen sowie Experten (wird bei allgemeiner Personennennung die männliche Form verwendet, ist stets auch die weibliche oder diverse Form gemeint) aus Mathematik, Bioinformatik, Chemie und Physik, um grundlegende Fragen zu Netzwerkstruktur, -dynamik und –regulation mit quantitativen Methoden zu beantworten. Unser Ansatz profitierte immens von der Kombination molekularer und bioinformatischer Ansätze und führte zu einem besseren Verständnis zellulärer Prozesse. Ein „bottom-up“ Prozess zur Identifizierung der kommenden Forschungsfragen, die im Rahmen des Clusters besonders gefördert wurden, führte zu sechs aufregenden Projekten, deren Ergebnisse drei neue Sonderforschungsbereiche und ein DFG gefördertes Netzwerk für Elektronenmikroskopie untertsützten. Eine Voraussetzung für diesen Erfolg liegt in der zusätzlichen Rekrutierung von exzellenten Wissenschaftlern bevorzugt an der Schnittstelle von Disziplinen (Professur für Proteinevolution) oder von Technologiespezialisten (Professuren für Cryo-Elektronenmikroskopie und Proteomik). Zusätzlich haben zehn Nachwuchsgruppen, finanziert durch das Cluster, und zehn Nachwuchsgruppen finanziert von der Chica und Heinz Schaller-Stiftung, eine äußerst anregende Forschungsumgebung für junge Wissenschaftler geschaffen. Unsere neuen Kollegen stimulierten die technologieorientierte Weiterentwicklung und dynamische Einbindung neuer Forschungsfragen in das Forschungsportfolio der molekularen Lebenswissenschaften in Heidelberg. Parallel dazu bildeten die zentralen Core Facilities mit den Bereichen des technischen Service, der Projektberatung und der techniknahen Ausbildung eine wichtige Verbindung zwischen Forschenden verschiedener Disziplinen und Statusgruppen der Universität und unserer Partnerinstitutionen. CellNetworks war, ist und wird eine treibende Kraft für die Integration der molekularen Biowissenschaften in Heidelberg sein und zwar über institutionelle und disziplinäre Grenzen hinweg. In Zukunft wird CellNetworks als zentrale Einrichtung der Universität Heidelberg die Core Technologie- Entwicklung anführen. Wir haben streng darauf geachtet, dass die CellNetworks Professuren, Leiter der Core Facilities und Mitarbeiterinnen des Projektbüros langfristig an der Uni Heidelberg tätig sind. Somit ist gesichert, dass nicht nur die Mitglieder des Clusters, sondern darüber hinaus die gesamte Forschungscommunity der Lebenswissenschaften in Heidelberg von CellNetworks weiterhin profitiert.

Link zum Abschlussbericht

https://dx.doi.org/10.2314/KXP:1697276407

Projektbezogene Publikationen (Auswahl)

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• HIV-1 Nef interferes with host cell motility by deregulation of cofilin. Cell Host Microbe. 2009 Aug 20;6(2):174-86
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• Hemoglobins S and C interfere with actin remodeling in Plasmodium falciparum-infected erythrocytes. Science. 2011 Dec 2;334(6060):1283-6
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• Nuclear calcium-VEGFD signaling controls maintenance of dendrite arborization necessary for memory formation. Neuron. 2011 Jul 14;71(1):117-30
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• Quantitative evaluation of mechanosensing of cells on dynamically tunable hydrogels. J Am Chem Soc. 2011 Feb 9;133(5):1367-74
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• Maturation-dependent HIV-1 surface protein redistribution revealed by fluorescence nanoscopy. Science. 2012 Oct 26;338(6106):524-8
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• SAMHD1 restricts HIV-1 infection in resting CD4+ T cells. Nat Med. 2012 Nov;18(11):1682-7
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• Structure and dynamics of the ATP-bound open conformation of Hsp70 chaperones. Molecular Cell. 2012 Dec 28;48(6):863-74
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• Synchronizing nuclear import of ribosomal proteins with ribosome assembly. Science. 2012 Nov 2;338(6107):666-71
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• Detecting endogenous SUMO targets in mammalian cells and tissues. Nat Struct Mol Biol. 2013 Apr;20(4):525-31
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• FHOD1 interaction with nesprin-2G mediates TAN line formation and nuclear movement. Nat Cell Biol., 2014 Jul;16(7):708-15
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• Alleviation of off-target effects from vector-encoded shRNA via co-delivered RNA decoys. Proc Natl Acad Sci USA. 2015 Jul 28;112(30):E4007-16
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• Cytoadhesion of Plasmodium falciparum-infected erythrocytes to chondroitin-4-sulfate is cooperative and shear enhanced. Blood. 2015 Jan 8;125(2):383-91. doi: 10.1182/blood-2014-03-561019
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• Fundamental properties of unperturbed haematopoiesis from stem cells in vivo. Nature. 2015 Feb 26;518(7540):542-6
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• LncRNA Khps1 regulates expression of the proto-oncogene SPHK1 via triplex-mediated changes in chromatin structure. Mol Cell. 2015 Nov 19;60(4):626-36
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• Mammalian SRP receptor switches the Sec61 translocase from Sec62 to SRP-dependent translocation. Nat Comms. 2015 Dec 4;6:10133
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• Mechismo: predicting the mechanistic impact of mutations and modifications on molecular interactions. Nucleic Acids Research, 43.2: e10, 2015
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• Modulation of Presynaptic Release Probability by the Vertebrate-Specific Protein Mover. Neuron. 2015 Aug 5;87(3):521-33
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• NS5A Domain 1 and Polyprotein Cleavage Kinetics Are Critical for Induction of Double-Membrane Vesicles Associated with Hepatitis C Virus Replication. MBio. 2015 Jul 7;6(4):e00759
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• The exosome is recruited to RNA substrates through specific adapter proteins. Cell. 2015 Aug 27;162(5):1029-38
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• Transcriptional refractoriness is dependent on core promoter architecture. Nat Commun. 2015 Apr 8;6:6753
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• Triggering HIV polyprotein processing by light using rapid photodegradation of a tight-binding protease inhibitor. Nat Commun. 2015 Mar 9;6:6461
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• Zincfinger nuclease-based double strand breaks attenuate malaria parasites and reveal rare microhomology mediated end joining. Genome Biology. 2015 Nov 17;16:249
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• (2016) MYC/MIZ1-dependent gene repression inversely coordinates the circadian clock with cell cycle and proliferation. Nat Commun. 2016 Jun 24;7:11807
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• A genetic interaction map of cell cycle regulators. Molecular Biology of the Cell, 2016
  Billmann M, Horn T, Fischer B, Sandmann T, Huber W, and Boutros M
  
• A New Population of Parvocellular Oxytocin Neurons Controlling Magnocellular Neuron Activity and Inflammatory Pain Processing. Neuron. 2016 Mar 16;89(6):1291-1304
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• ARHGEF17 is an essential spindle assembly checkpoint factor that targets Mps1 to kinetochores. J Cell Biol. 2016 Mar 14;212(6):647-59
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• Blocking sense strand activity improves potency, safety and specificity of anti-hepatitis B virus short hairpin RNA. EMBO Mol Med. 2016 Sep 1;8(9):1082-98
  Michler T, Grosse S, Mockenhaupt S, Röder N, Stückler F, Knapp B, Ko C, Heikenwälder M, Protzer U, and Grimm D.
  
• Dengue Virus Perturbs Mitochondrial Morphodynamics to Dampen Innate Immune Responses. Cell Host Microbe. 2016 Sep 14;20(3):342-356
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• Differential use of the C-type lectins L-SIGN and DC-SIGN for phlebovirus endocytosis. Traffic. 2016 Jun;17(6):639-56
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• Dnmt3a2: a hub for enhancing cognitive functions. Mol Psychiatry. 2016 Aug;21(8):1130-6
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• Expanding the Circuitry of Pluripotency by Selective Isolation of Chromatin-Associated Proteins. Mol Cell. 2016 Nov 3;64(3):624-635
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• Force-producing ADP state of myosin bound to actin. Proc Natl Acad Sci USA. 2016 Mar 29;113(13):E1844-52
  Wulf SF, Ropars V, Fujita-Becker S, Oster M, Hofhaus G, Trabuco LG, Pylypenko O, Sweeney HL, Houdusse AM and Schröder RR
  
• Frequent mechanical stress suppresses proliferation of mesenchymal stem cells from human bone marrow without loss of multipotency. Sci Rep. 2016 Apr 15;6:24264
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• Integration of light and metabolic signals for stem cell activation at the shoot apical meristem. Elife. 2016 Jul 11;5. pii: e17023
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• MTHFD1 controls DNA methylation in Arabidopsis. Nature Comm. 2016 Jun 13;7:11640
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• Oxidative insult can induce malaria-protective trait of sickle and fetal erythrocytes. Nat Commun. 2016 Nov 8;7:13401
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• Reovirus intermediate subviral particles constitute a strategy to infect intestinal epithelial cells by exploiting TGF-β dependent pro-survival signaling. Cell. Microbiol. 2016 Dec;18(12):1831-1845
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