Cytoskeleton dependent RNA distribution mechanisms
Cell and Developmental Biology
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Cytoskeleton dependent RNA distribution mechanisms
2011-2013: Postdoc in the laboratory of Dr. Surrey, London Research Institute (LRI), London, United Kingdom
2008 - 2010 : Postdoc in the laboratory of Dr. Surrey, European Molecular Biology Laboratory, (EMBL), Heidelberg, Germany
2005 - 2008: PhD in Biochemistry in the laboratory of Prof. Muskhelishvili , Jacobs University, Bremen, Germany
1999 - 2004: Diploma studies in Biochemistry, Phillips Universität, Marburg, Germany
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Maurer is interested in understanding the molecular mechanisms underlying cytoplasmic RNA transport along cytoskeletal elements. His expertise and innovative approach within this field will be vital to carry out the HSFP awarded project.
Summary
Maurer's lab website: https://maurerlab.net/
Different cell types localize and locally translate up to 1000s of different mRNAs, a mechanism which leads to distinct protein distributions in different parts of the cell. The ability to control the protein configuration of different cell regions individually allows the cell to create domains with specialized functions. Prominent examples of cell regions for whose functionality RNA localization was shown to be crucial are axons and dendrites. Here the right localisation of a certain RNA population is important for memory formation and maintenance while mutations affecting components of RNA transport systems lead to severe neurodegenerative diseases.
Our laboratory is interested in the molecular mechanisms underlying cytoplasmic RNA transport along cytoskeletal elements, especially microtubules. Many unsolved questions surround cytoplasmic RNA transport which include: What is the minimal set of components needed to transport a RNA? How do motors select which RNA to transport? How is the amount of transported RNAs regulated?
A wealth of in vivo data is available, providing examples of RNA transport systems and their biological relevance. However, an understanding of how involved factors are steering RNA distribution on the molecular level is often hindered by the complexity of the cell. Complementary to in vivo research in the field, our laboratory employs a bottom-up strategy. Purified RNAs and proteins are used to assemble RNA transport modules having a controlled number of components in vitro. Properties and function of factors building such RNA transport modules are studied by combining fast simultaneous multi-colour Total Internal Reflection Microscopy (TIRF-M) and structural studies.
Fig.1 Example of a TIRF-M movie. The transport of a fluorescently labelled cargo (cyan) by a kinesin motor protein towards microtubule plus ends is visualized here.
Fig.2 Simplified schematic illustrating essential steps in RNA transport. (1) A RNA (bright grey), RNA binding proteins (green) and other adaptor proteins (yellow) form complexes (2) RNA-protein complexes are loaded onto motor proteins (orange) (3) RNA-protein complexes are transported along microtubules by motor proteins (4) RNA-protein complexes are stored or unpacked at their destination.
Projects are available investigating four crucial steps of RNA logistics:
- RNA-packing: Which proteins bind and protect the RNA molecule to guide it through the cytoplasm ? How does the interaction happen ?
- Loading onto a vehicle: How is the choice of motor controlled ?
- Moving along a highway: How is transport of many different RNA cargoes coordinated ?
- Delivery of cargo: When is the destination reached and which mechanisms control storage or release of the RNA cargo?
Highly skilled and motivated students, curious about the mechanistic foundation of cellular processes, are welcome to apply. Students with a sound background in Biochemistry are of special interest.
