Yearbook 2005

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Genome-wide Screens as a systematic approach to study key mechanisms in biology

Max Planck Institute of Molecular Cell Biology and Genetics Buchholz, Frank; Kittler, Ralf; Putz, Gabriele; Pelletier, Laurence; Poser, Ina; Heninger, Anne-Kristin; Drechsel, David; Fischer, Steffi; Konstantinova, Irena; Habermann, Bianca; Grabner, Hannes; Yaspo, Marie-Laure; Himmelbauer, Heinz; Korn, Bernd; Neugebauer, Karla; Pisabarro, Maria Teresa
Genom-wide screens are a major and significant part in modern biology. They provide a perfect tool to study the function of various genes with clinical relevance and in key mechanisms in the cell. The Max Planck Institute for molecular cell biology and genetics (MPI-CBG) has built up a Screening Facility that serves as a European screening resource for the research community. An esiRNA screen in human cells performed by the research group of Frank Buchholz has identified genes essential for cell division. Results like that have major clinical relevance, and a medical implication especially for cancer research, since malfunctions of the mechanisms underlying cell division are the cause for cancer. The MPI-CBG has found the right partners to build up this screening project – Dr. Ivan Baines, Director of Services and Facilities at the MPI-CBG, brought together expertise from the industry and excellent basic research to form a new model that is well-equipped to find answers to the very complex questions in modern biology. more
The development of a complex animal from a single egg cell requires both cell division and cell specialization to produce the different organs and structures required for adult life. In order to be able to complete such developmental programs cells must be able to receive and correctly interpret instructions; instructions that are mediated by a relatively small group of evolutionarily conserved signal transduction pathways. One of these, and the focus of research in the laboratory of Martin Zeidler, MPI for Biophysical Chemistry in Göttingen, is the JAK/STAT pathway. The JAK/STAT signalling pathway plays important roles during early embryonic development and is required for the production of blood cells and the function of the immune system. Furthermore, its mis-activation is responsible for a large proportion of human leukaemias and lymphomas. As such, a better understanding of the pathway and the mechanisms that control its activity is potentially significant to human health. Zeidler and his colleagues use the evolutionary conservation common to all signalling pathways to identify and characterise the regulators of JAK/STAT signalling in the fruit fly Drosophila melanogaster. By exploiting the genetic and molecular tools available toDrosophila researchers they have undertaken screens to identify genes required for pathway activity. They have also undertaken detailed, in depth analysis of a subset of these molecules in their normal developmental context. As such the scientists are improving understanding of this important signalling cascade to allow people to better diagnose and treat the diseases it can produce. more
A minor part of the pancreas is responsible for the secretion of hormones, such as insulin, to regulate the bloodsugar level. The mouse is used as an animal model to identify factors that drive the cellular subtype identity of these different hormone-producing cells. Two transcription factors Arx and Pax4 are required for the proper and coordinated development of these cells. more
The junior research group has been examining several aspects of tropical tropospheric chemistry using two 3D models. Here an overview of the results is given, focusing particularly on two central activities of the group: 1) the outflow of pollutants from southern Asia and the factors controlling pollution over the Indian Ocean; 2) the role of deep convection in tropospheric chemistry, especially in the tropics, and its treatment in cloud-resolving and global models. more
Novel in-situ mass spectrometric techniques offer new possibilities for the investigation of traffic related particle emissions. Measurements performed on an engine test facility showed that ultrafine particles (<100 nm) in diesel exhaust consist of freshly nucleated compounds as sulfuric acid and organics, which have been emitted as gaseous substances. Since it was found that the formation efficiency of these nucleation particles is strongly dependent on the fuel sulfur content, it was concluded that sulfuric acid plays a major role in this process. Measurements of mass concentrations and size distributions of various aerosol compounds in the vicinity of a German motorway and in New York City showed the various influences of traffic emissions on the composition of ambient aerosol in the different size ranges at different times. more
When we are about to cross a road and think about waiting for the next car or not, we have to coordinate two predictions at the same time. We anticipate both how things will change in our environment and how we will change things in our environment. However, brain activation shows that even if we do not plan to cross the road we still activate the same brain regions – those for action planning. Brain imaging addresses this phenomenon and tries to tackle the question as to why some cognitive functions make use of genuine motor regions of the brain. more
Psychology and experimental economics have taught us a lot about the behaviour of individuals. Yet in our social environment we rarely meet isolated individuals. We usually face corporate actors. This holds even more for government. Yet we know fairly little about the behaviour of corporate actors. more
Nanoparticles play a crucial role in the development of advanced materials and devices. The reason lies in the fact that particles just a few nanometres in size exhibit different chemical and physical properties compared to the bulk material. The wide variety of applications of metal oxides in catalysis, sensing, energy storage and conversion, optics and electronics moved this class of materials into the centre of interest of materials science. In order to obtain metal oxides in form of nanoparticles with well-defined shape, size and crystallinity, the traditional synthesis routes are hardly suited, and novel innovative strategies have to be developed. In comparison to the complex aqueous chemistry, the synthesis of metal oxide nanoparticles in organic solvents offers the possibility to better understand and to control the reaction pathways on a molecular level, enabling a rational synthesis design for inorganic nanoparticles based on organic chemistry. more
Amphiphilic molecules contain a hydrophilic headgroup and a hydrophobic tail. The prevailing molecular asymmetry leads to a spontaneous adsorption of amphiphiles at the air-water or oil-water interface. As a result, the surface tension and the surface rheology are changed. We are using soluble amphiphiles as model systems to study fundamental interactions in colloid and interface science. An example is the distribution of ions at a charged interface. The puzzling ion specific effects are the result of a subtle balance of several competing evenly matched interactions consisting of a complex interplay of electrostatics, dispersion forces, thermal motion, fluctuations, hydration, ion size effects and the impact of interfacial water structure. Furthermore we try to identify correlations between observed macroscopic and the corresponding molecular properties of the adsorbed species. Surfactants enable phenomena such as foaming or emulsions. Foams can only be formed if surface active materials are present. The stability of foams is not yet completely understood and we believe that the surface rheology plays a decisive role. In the last years we developed several novel experiments to study surfactant dynamics and surface rheology. more
Crimes orchestrated by well-isolated “persons behind the scenes” and carried out within the framework of complex organizational structures pose special challenges to both the theory and the practice of criminal law. Important cases within this context are the crimes committed in civil wars. The prosecution of the crimes committed in the Balkans before the Yugoslavia Tribunal provided the incentive for a comprehensive comparative legal study of over forty criminal justice systems. The innovative approach taken by this research project combines the examination of theoretical underpinnings with an analysis of hypothetical case scenarios. more
New results demonstrate that those regions of the brain uniquely devoted to the processing of a single sense are rarer than classically thought. Instead, most of the brain is concerned with merging information across senses and creating a coherent percept. more
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