Biochemie-Zentrum der Universität Heidelberg (BZH)

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An automated platform for the crystallization of biological macromolecules The Cluster of Excellence CellNetworks and the group of Prof. Dr. Irmgard Sinning are establi- shing a state-of-the-art high throughput crystallization platform for biological macromolecules at the BZH. Dr. Jürgen Kopp will run the facility assisted by Claudia Siegmann. The platform will be open from May 2008 for the scientific community in and around Heidelberg. It will include a nano-dispensing pipetting robot (Phoenix Rigaku Edition) which allows screening of 1000 crystallization conditions with as little as 100 microliters of sample within one hour. The crystallization experiments are stored at defined temperatures in two Rigaku Minstrel HT Galleries with a capacity of up to 800 plates and will be automatically imaged. 48 Facilities The images can be viewed via the web and users can design follow-up experiments assisted by specialized software. Standard commercial and user defined screens will be available for soluble proteins, macromolecular assemblies as well as for membrane proteins. For more information, visit the BZH homepage and the web portal of the CellNetworks Cluster. Irmgard Sinning Biochemie-Zentrum der Universität Heidelberg (BZH) Im Neuenheimer Feld 328 D-69120 Heidelberg Phone: +49 (0)6221-54 4781 Fax: +49 (0)6221-54 4790 E-mail: irmi.sinning@bzh.uni-heidelberg.de
Funding Sonderforschungsbereich (SFB) 638: Dynamics of macromolecular complexes in biosynthetic transport Chairman: Felix Wieland, Biochemie-Zentrum der Universität Heidelberg (BZH) Cells are highly dynamic structures that can be compared with factories full of sophisticated machines. In the last decades many individual parts of these machines have been identified and characterised. In the years to come the most excit- ing challenge will be to decipher how individual building blocks are put together in variable ways to perform the cell´s dynamic functions. This is done in an iterative way: one first tries to com- bine the single parts to functional assemblies; once an assembly is defined functionally, such assemblies are combined to even higher aggre- gates at a next layer of complexity, again functionally characterised, and so on. With a hundred thousand or so different proteins that build up a human cell, and up to 200 parts comprising a macromolecular complex (a functional unit), it is evident that there is still a long way to go in order to completely understand not only the compositions of all possible functional units, but also their interplay, i.e. their dynamics. With this knowledge complete, we would understand the molecular basis of life, and to prove our understanding, we would have to reconstitute a living cell from its defined building blocks. This would have to occur not only by adding each component in exactly the correct concentration, but also in a defined sequence, because of their dynamics many of the assemblies can only function correctly in a timedependent manner. Needless to say that such a task could be solved only by the activity of many scientists worldwide, and final success, if possible at all, lies in the far future. Along this way, the SFB 638 “Dynamics of Macromolecular Complexes in Biosynthetic Transport” has initiated an interdisciplinary approach to investigate the structural and dynamic behaviour of complexes of up to 100 or so components within a cell. Even if none of the scientists involved is likely to reach the final goal, we believe that many important lessons can be learned during this journey. The expertise existing in Heidelberg has led us to focus our research on biosynthetic transport. In this context we use the term dynamics at two levels: I) dynamics of macromolecular complexes (e.g. their conformational change, or their assembly and disassembly), and ii) the dynamics of the interplay of macromolecular complexes during their further assembly or disassembly to form functional subcellular structures (e.g. formation and transport of a pre-ribosomal assembly through the nuclear pore, the formation or disassembly of a coated membrane carrier, or the formation and transport of a virus particle). Biosynthetic transport is a cellular housekeeping function of special interest with respect to medical research, because many congenital diseases are caused by defects in transport machinery and biosynthetic transport is exploited at various steps by pathogenic viruses for productive infection and synthesis of viral progeny. Thus, our SFB brings together research groups using structural, cell biological, biochemical, molecular biological and virological methods and analysing various model organisms, from bacteria via yeasts to mammalian cells. Our collaborative approach allows integration of colleagues coming from different fields in the life sciences, driven by their common research interest. As a result, exchange between the groups of a wide range of knowledge and methodology is achieved naturally, and this, combined with the common interest, fosters creativity and at the same time strengthens a competent and critical view to evaluate results. Funding 49
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