<interact> 2009 brought together 400 enthusiastic life science graduate students on the 2nd of April 2009 at the majestic main building of the Ludwig Maximilians University and give them a platform to brainstorm, discuss and talk about science. This follow up to 2007 proved to be an equally successful event, with keynote lectures from Alfred Wittinghofer (MPI of Molecular Physiology, Dortmund) and Nobel laureate Tim Hunt (Imperial Cancer Research, London). The diversity and depth of the field of life sciences was well represented in the 7 graduate student talks and 140 posters that encompassed topics such as immune system regulation, cytoskeleton dynamics and protein integrity. Munich's strong reputation as a life science center was well apparent by participants from all of the seven life science institutes including the Max Planck Institutes of Biochemistry, Neurobiology and Psychiatry, the Munich Universities and the Helmholtz Zentrum. The event was supported by contributions from both academia and industry. Based on this year's response and success, the organizers have announced that the <interact> symposium would now take place on an annual basis. It has already been confirmed that next year Susan Lindquist, a pioneer in protein folding, from the Whitehead Institute for Medical Research (MIT, Boston) will be addressing the 2010 Interactees.
Tim Hunt works at Cancer Research UK in London and investigates cyclin-dependent protein kinases (CDKs), cell cycle transitions, and the timed proteolysis of cyclin. In 2001 he was awarded the Nobel Prize in Physiology or Medicine. What Tim Hunt liked about Chemistry at school was his teacher’s emphasis on principles, rather than facts. This became a defining feature of his science later on in life. He established a simple principle of cell cycle regulation: entry into mitosis requires the making of an enzyme, and getting out of mitosis requires its destruction. These cell cycle regulatory enzymes are known as cyclins and their associated cyclin-dependent protein kinases as CDKs. When Tim started his scientific career in 1964 as a biochemistry PhD student in Cambridge he had no idea that he would end up studying the cell cycle. His primary interest lay in the control of translation of mRNA. Using rabbit reticulocytes for studies of haemoglobin synthesis he learned to appreciate the advantages of simple model systems. He found that ribosomes are evenly spaced along globin mRNA, and never formed a queue, unless forced to do so. After his PhD in 1968 he moved to New York and continued to work on translational control where he made the curious discoveries that addition of tiny amounts of oxidized glutathione or double-stranded RNA entirely killed protein synthesis in reticulocyte lysates. Years later the effect of oxidized glutathione was linked to a loss of reduced NADP and glucose-6-phosphate involving the action of thioredoxin and thioredoxin reductase. Concerning the inhibition by dsRNA, it was most striking that high levels of dsRNA did not inhibit protein synthesis although amounts as low as one molecule per lysed cell equivalent were sufficient to be effective - early signs of RNAi looming on the horizon. It eventually turned out that inhibitory protein kinases lay behind the control of haemoglobin synthesis. Towards the end of the 1970s Tim concentrated on changes in protein synthesis in sea urchin and clam eggs after fertilization. In 1982 a simple experiment changed his scientific life. Asking the question whether the proteins made after fertilisation were the same as the ones made after parthenogenetic activation of the eggs, he noticed a protein band in the autoradiographs that, contrary to all the others, got weaker and disappeared. Later that same day, John Gerhart told him about the activity of MPF that he and Marc Kirschner were studying in Xenopus oocytes. MPF activity vanished between meiosis I and meiosis II, and needed new protein synthesis to reappear, potentially linking Tim’s discovery on the protein level to a physiological entity. What followed was an extensive characterisation of this and other “cyclins” and finally, in 1986 the cloning and sequencing of sea urchin cyclin B. The activity in Xenopus oocytes was shown to contain a B-type cyclin as well as p34cdc2. In 1995 the crystal structure of cyclin A in complex with CDK2 was solved by Nicola Pavletich’s group at the Memorial Sloan-Kettering Cancer Center in New York. For his ground-breaking work, Tim Hunt was awarded the Nobel Prize in Physiology or Medicine in 2001, together with Leland Hartwell and Paul Nurse. Continuing work on cell cycle control at Cancer Research UK, London, Tim’s focus is now on the structure, function and destruction of CDKs that control the onset of mitosis and the return to interphase. Following a chance discovery of the involvement of the calcium-activated protein phosphatase (calcineurin) at fertilization, he is now very interested in how the mitotic phosphorylations put on by CDKs are taken off at the end of mitosis, and how futile cycles are avoided; the flipflop switches that ensure either high kinase activity (in mitosis), or high phosphatase activity (in interphase).
Alfred Wittinghofer has made major contributions to the field of GTP-binding proteins, among them the proto-oncogene Ras, known to be involved in a broad spectrum of human cancers. In his lab, both biophysical and biochemical methods such as NMR, fluorescence and X-Ray crystallography are applied. Alfred Wittinghofer studied chemistry and received his PhD degree from the German Wool Research Institute (German acronym: DWI) in Aachen with a dissertation on the chemical synthesis of insulin. In 1971 he became a postdoctoral fellow at the University of North Carolina, where his main research interest was the modification of proteins. In 1974 he returned to Germany to work as a research staff member at the Max Planck Institute for Medical Research in Heidelberg. In 1980 he became a group leader and focused on the structure-function relationship of oncoproteins and on GTP-binding proteins. In 1992 he qualified as professor at the University of Heidelberg. Since 1993 he has been head of the Department of Structural Biology at the Max Planck Institute of Molecular Physiology in Dortmund. The subjects of his work at the MPI Dortmund are functional, mechanistic and structural studies on GTP-binding proteins and their regulatory factors and effectors. The GTP-binding oncoprotein Ras is a signal transduction protein and controls intracellular signalling networks, that regulate actin cytoskeletal integrity, proliferation, differentiation, cell adhesion, apoptosis, and cell migration. Ras acts as a binary molecular switch, that can signal-dependently be turned on by Guanine nucleotide exchange factors (GEFs) and GTP-binding or turned off by GTPase activating proteins (GAPs) and GDP-binding. Point-mutations can lead to unlimited cell growth and cancer. Wittinghofers group analyses Ras´ conformational changes by X-ray and NMR methods and was thereby able to solve the three-dimensional structure of Ras-GTP and to describe the nature of the conformational change in GTP-binding proteins. He also focuses on interactions of Ras with GAPs, GEFs and effectors with biochemical methods and X-ray analysis and thereby enables the description of Ras-RasGAP complex-structure, of GAP-mediated GTP hydrolysis-mechanisms (and why the reaction is blocked in oncogenic mutants of Ras) and of kinetic mechanisms of the Ras-GEF reaction. The structure of Ras-effector complexes and the thermodynamics and kinetics of effector complexes is also dealt with in his group and leads to studies for the development of anti-Ras drugs. Another small GTPase, Ran, which is a nuclear transport regulator, is also characterized in Wittinghofers department to elucidate its role in nuclear transport. The structure of the Ran-RCC1 (GEF) complex and the mechanism of the GEF reaction are investigated by structural and kinetic studies and the Ran-RanGAP interaction by structural and biochemical analysis. Also the mechanism of the RanGAP mediated reaction and studies on Ran-effector complexes like Ran-Importin and Ran-RanBD are part of Wittinghofers work and led to a high number of published structures and explanatory mechanistic models. Besides the described GTP-binding proteins, Wittinghofers team investigates other GTP-binding proteins like the Ras homologous protein Rap, which regulates cellular processes like adhesion, migration, cell-cell-contacts and proliferation. This research includes solving structures of Rap-effector complexes and its thermodynamics and kinetics, but also the investigation of the RapGAP-mediated GTP hydrolysis mechanism and studies on the cAMP responsive Rap-specific GEF Epac. Another topic of his science are structural and mechanistic studies on effectors of Rac, Cdc42 and Rho, such as WASP, PAK and mDIA and the activation of effectors. Also structural studies on bacterial GEFs and GAPs for eukaryotic Rho proteins are developed in Wittinghofers group. His group also investigates the Human Guanylate Binding Protein as a model for polymerizing GTP-binding proteins. Other projects deal with the filament-forming Septins, with the function of Arl proteins and with the structures of Arl2/3 and complex with PDE. Alfred Wittinghofer is honorary professor of biochemistry in the Department of Chemistry of the Ruhr University Bochum since 1993. He has received several awards, including the Jouis-Jeantet Prize (2001), the German Cancer Prize (2003), and the Otto Warburg Medal of the Society for Biochemistry and Molecular Biology (2003).
We congratulate the winners of the speakers and Poster prizes of the 2009 Munich <interact> PhD symposium.
Dominik Paquet "A zebrafish model of Alzheimer′s Disease"
Olympus SLR Camera
In the meantime Dominik published his research presented at the symposium in JCI (2009) 119(5):1382-1395: "A zebrafish model of tauopathy allows in vivo imaging of neuronal cell death and drug evaluation"
Jens Frauenfeld (Best Science Poster)
"Cryo-EM of an active 70S ribosome-SecYEG complex in its membrane environment"
Yvonne Kienast (Best Method Poster)
"Brain metastasis formation: Real-time imaging reveals mandatory, inefficient and unsuccessful steps"
In the meantime Yvonne published her research presented at the symposium in Nature Medicine (2010) Jan;16(1):116-22: "Real-time imaging reveals the single steps of brain metastasis formation".
Birgit Ebert (Best Poster Presentation)
"The role of mitochondrial dysfunction in astrocytes — a mouse model for brain ageing"
Source Event London
Mareike Fett (Best Poster Presentation)
"A novel vertebrate model to study the function of parkin"
Source Event Berlin
In the meantime Mareike published her research presented at the symposium in PLoS One. 2010 Jul 30;5(7): "Parkin is protective against proteotoxic stress in a transgenic zebrafish model".
Ivana Nikic (Best Poster Presentation)
"In vivo imaging of neuro-immune interactions in an animal model of multiple sclerosis"