AUTOHEPARIN (ERC-2008-AdG) Automated Synthesis of Heparin and Chondroitin Libraries for the Preparation of Diverse Carbohydrate Arrays

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1 ERC grantees based in Berlin/ Potsdam Prof. Peter H. Seeberger Max Planck Institute of Colloids and Interfaces AUTOHEPARIN (ERC-2008-AdG) Automated Synthesis of Heparin and Chondroitin Libraries for the Preparation of Diverse Carbohydrate Arrays Advanced Grant Start date 01/01/2009 EU contribution EUR While heparin, a glacosaminoglycan (GAG) has served as an anticoagulant for more than 60 years, the structure-activity relationship of heparin and chondroitin sulfate for specific interactions with proteins are still poorly understood. It has become evident that defined lengths and sequences or patterns are responsible for binding to a particular protein and modulating its biological activity. Determination of the structure-activity relationships of heparins and chondroitins creates an opportunity to modulate processes underlying viral entry, angiogenesis, kidney diseases and diseases of the central nervous system. The isolation of pure GAGs is extremely tedious and chemical synthesis is often the only means to access defined oligosaccharides. Currently available synthetic methods for the preparation of heparins and chondroitins are time consuming and lack generality. Therefore, it is still impossible to create large collections of GAG oligosaccharides for systematic studies of GAG-protein interactions. The overall goal of the project is the development of all aspects of automated GAG synthesis, the procurement of a large collection of heparin and chondroitin oligosaccharides of 2-10 sugars in length with a linker for ready attachment to microarray surfaces and other tools. These molecular tools will be employed to study the interaction of GAGs with growth factors, chemokines and other proteins. The specific aims include: Synthesis of uronic acid and galactosamine building blocks; Development of a new linker for automated GAG solid phase synthesis; Construction of a new automated oligosaccharide synthesizer; Development of methods for the automated assembly of heparin and chondroitin sulfate oligosaccharides; Synthesis of a collection of defined heparin and chondroitin sulfate oligosaccharides; Construction of synthetic GAG microarrays and SPR; Preparation of GAG dendrimers and quantum dots. Prof. Dr. Peter H. Seeberger Max Planck Institute of Colloids and Interfaces Department of Biomolecular Systems Research Campus Potsdam-Golm D Potsdam Assistant: Dorothee Böhme Fon: Fax:

2 Number of Grants: 6 Dr Francesca M. Spagnoli HEPATOPANCREATIC (ERC-2009-StG) Mechanisms Underlying Cell Fate Decision Between Pancreas and Liver Starting Grant Start date 01/11/2009 EU contribution EUR Diabetes is a degenerative disease affecting millions of persons worldwide. A cure for diabetes depends on replacing the insulin-producing β-cells in the pancreas that are destroyed by the disease. An attractive strategy to attain this goal is to convert liver adult cells of the same patient into pancreatic β-cells. The liver and pancreas share many aspects of their early development and are specified in adjacent regions of the endoderm, possibly from a common bipotent progenitor cell. Therefore, conversion of liver to pancreas is conceivable and should imply only few steps backward to a common progenitor and little epigenetic changes. However, how pancreatic versus hepatic fate decision occurs during development is still poorly understood. The aim of this proposal is two fold: to perform lineage analysis, and to study developmental regulators of pancreatic versus hepatic fate decision. We will use new genetic tools, based on the GFP and photoconvertible Kaede fluorescent proteins, to address: i. if the liver and pancreas arise from a common bipotent progenitor cell; ii. to trace in vivo; iii. to molecularly profile the presumptive precursor cell and its descendants in the mouse embryo. Our previous studies have identified target genes of the GATA factors that might act as intrinsic developmental regulators of the pancreatic versus hepatic fate decision. Both intrinsic factors together with extrinsic regulators, such as BMP, will be studied. We will test their potential to promote lineage reprogramming of liver to pancreas using the mouse as well as mouse embryonic stem cells as model systems. Understanding how distinct cell types arise from common multipotent progenitor cells is a major quest in developmental biology. Our findings will elucidate the spatiotemporal mechanisms that control pancreas versus liver fate decision. In addition, they will provide the blueprint for lineage reprogramming of adult hepatic cells to pancreas in the context of diabetes cell-therapy. Contact details of Dr. Spagnoli are available by clicking here.

3 Dr Matthew Poy IsletVasc (ERC-2010-StG) Molecular Mechanisms Regulating Pancreatic Islet Vascularization Starting Grant Start date 01/11/2010 EU contribution EUR Many reports indicate the number of people with diabetes will exceed 350 million by the year Both type 1 and type 2 diabetes are characterized by the deterioration and impaired function of pancreatic β-cells. While transplantation is a promising strategy to replace lost tissue, several obstacles remain in the pathway to its clinical application. Whether β-cells are derived from patient samples or differentiated from embryonic stem cells, a major concern facing these strategies is how a recipient will respond to transplanted foreign tissue. Since the native environment for pancreatic islets is comprised of neural and vascular networks, successful integration may depend upon signals received from these neighbouring cell types. Using a multidisciplinary approach, the principal investigator plans to elucidate molecular mechanisms underlying the interactions between pancreatic islet cells and their neighbouring endothelial cells. Developing an understanding of how these interactions change during the pathogenesis of disease will provide insight into how islet growth and insulin release is dependent upon signals received from adjacent cell types. Emphasis will be placed on genetic mouse models to measure changes in gene expression in both isolated pancreatic β- cells and endothelial cells to identify genes that mediate the interaction between these cell types. In addition, it is of great interest to identify secreted factors that may constitute autocrine or paracrine signalling mechanisms that influence growth and function between these cell types. Furthermore, it will be determined whether current protocols for the differentiation of mouse stem cells into insulin producing cells are improved by restoring the expression of genes which facilitate communication to endothelial cells. This project aims to identify genes essential to the vascular context of pancreatic β-cells to improve transplantation protocols and facilitate the development of therapeutic strategies for diabetes. Contact details of Dr. Poy are available by clicking here. Dr. Michael Brecht Humboldt-Universität zu Berlin Neuro-behavior (ERC-2008-AdG) From Neuron to Behavior Advanced Grant Start date 01/02/2009 EU contribution EUR

4 In the present proposal I will describe a novel research agenda for understanding the neural basis of mammalian behaviour. Three central problems prevent current research from explaining mammalian behave or in terms of neural mechanisms. First, there is a preponderance of correlative evidence in systems neuroscience. Second there is generally insufficient information about the individual neuron(s) under study. Third, there is a lack of integration of information. Current neuroscience is characterized by strongly diverging research interests and this highly divergent and specialized research program cannot lead to systemic understanding of brain function. We will confront these problems by three novel research approaches: We will establish a causal link between cellular activity and behaviour by a single-cellstimulation / reverse physiology approach. We will obtain rich information about single neurons by whole-cell recordings in awake behaving animals. We will perform a whole-brain analysis of a novel model organism, the Etruscan shrew, in which we will record the activity of all neurons in the shrew s brain. The research proposed here is unique, because as no other research group investigates brain function by a single-cell-stimulation, by intracellular recordings in freely moving animals, or by whole-brain analysis. The research outlined here will probe the relationship of neural activity and behaviour in an entirely unprecedented fashion. Prof. Dr.-Ing. Paschereit Technische Universität Berlin GREENEST (ERC-2009-AdG) Gas turbine combustion with Reduced EmissioNs Employing extreme STeam injection Advanced Grant Start date 01/07/2010 EU contribution EUR More new power-generation installations, less greenhouse gas CO2 emissions Global energy consumption is continuously increasing, leading to an increased world wide demand for new power generation installations in the near future. In order to protect the earth s climate, energy conversion efficiency and the use of sustainable resources have to be improved significantly. Gas turbines play today, and even more in the future, a major role in energy generation, but still far from efficiency at low NOx (Nitrogen Oxides) emission. The challenge is to get improved energy conversion efficiency and a larger use of sustainable resources, at low cost. The ERC project GREENEST investigates the fundamentals which are needed to develop the technology for a prototype combustor which is capable of burning natural gas, hydrogen and fuels from coal or bio-waste gasification at low NOx emissions. Research will include the combustion process, the aerodynamic design, acoustics and control. LINKS: ERC Grantee contact details:

5 Prof. Dr.-Ing. C. O. Paschereit postal address Fachgebiet Experimentelle Strömungsmechanik Institut für Strömungsmechanik und Technische Akustik Technische Universität Berlin Sekretariat HF1 Müller-Breslau-Straße 8 D Berlin Office Room HF ckick here office hours: Mo-Fr 09:00 AM - 01:00 PM Tel.: +49 (0) Fax: +49 (0)