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Function and regulation of promyelocytic leukemia (PML) nuclear bodies (NB) and their role in innate immunity and antiviral resistance


Promyelocytic leukemia (PML) nuclear bodies (NBs) are a sub-nuclear organelle implicated in various functions ranging from an active role in transcription, DNA repair, DNA replication and RNA transport, to a purely passive role as intra-nuclear depots for certain proteins. PML bodies are composed of several proteins and some of them can be strongly induced by interferons. The assembly of these proteins into NBs depends on the covalent modification by the protein SUMO. Several viral proteins localise to NBs but it is unclear whether these viruses use PML-bodies for their own replication or whether PML-bodies have a role in antiviral defence. This project aims to assess the function of PML-bodies by investigating the mechanism of their assembly. The starting point will be a detailed mapping of the interaction beween NB-associated proteins with biochemical and biophysical methods. In order to study the impact of the SUMO-modification on the assembly of PML-bodies a co-expression system will be established that allows the production of SUMO-modified proteins from in bacteria. The information on the assembly of PML-bodies will be verified in vivo using transfected cells and form the basis for a protocol to purify NBs from cells and tissues for further studies regarding their composition and function. The understanding of the function of PML-bodies will be a basis for the design of novel therapies against viral infectious diseases. The project will be funded by the interdisciplinary Centre for Molecular Medicine of the University of Cologne where Dr. Gerrit Praefcke being is going to establish an independent junior research group hosted by the Institute for Genetics. Funding includes initial equipment of the lab, positions for up to four staff and consumables for a duration of five years. After his training period of 2.5 years abroad this will enable Dr. Praefcke to work scientifically independent and to pursue an academic career in his home country.

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