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Research Activities at the Faculty

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Research Activities at the Faculty

Institute of Biochemistry

In 2004 the structure of the institute of biochemistry has been changed. As accepted by the senate of the University of Leipzig the chair of Microbiology is now part of the institute of biochemistry. However, the position in Microbiology is still vacant, in con-trast to the chair of Molecular biology/Biochemistry. Fortunately Prof. Dr. Mario Mörl accepted the professorship of Molecular biology/Biochemistry in December 2004. The re-opening of the professorship for Metabolism biochemistry/Enzymology is still in progress. Whereas in 2003 many groups moved, the groups could focus on their work in the new laboratories in 2004. However, in 2005 more moves are planed. Ac-cordingly, planning was also dominant in 2004 as for the new rooms in Talstraße 33 for the group of Prof. Hofmann and the special laboratories in the novel building Stephanstraße for the groups of Beck-Sickinger and Mörl. Further important issues in 2004 have been the preparations for the introduction of the novel consecutive bache-lor/master courses in biochemistry.

The group of Beck-Sickinger was very successful in the field of carrierpeptides. Within the EU-Project "Peptide Carrier for Drug Delivery" the uptake of DNA plasmids and aptamers into mammalian cells could be achieved by using carrier peptides. Fur-thermore the mechanism of uptake could be elucidated by biophysical and cell bio-logical methods. The development of selective ligands was very successful in 2004 in the field of orexins. The smallest orexin-receptor2 selective analogues as well as the first and only orexin-receptor1 compound have been identified. Within an interna-tional consortium the group of Beck-Sickinger contributed to important data clarifying the role of PYY in food intake. These data have been published in Nature. Further-more, the first selective biotinylation of aldoketoreductase was achieved. This will allow for the first time a selective immobilisation of the enzyme. Important advances have been again obtained in the field of selective radiolabelling that led to several publications and the acceptance of a patent.

Our research activities let to two major results: (i) the development of a novel compu-tational approach that allows for efficient screenings of virtual substrate mimetic li-braries for identifying improved types of substrate mimetics that can be used for the semisynthesis of peptides and proteins and (ii) the development of an enzyme-based approach to the selective C-terminal modification of native proteins which does not suffer from the well-known limitations of the intein-system used so far for this type of reaction.

The group of Robitzki has enlarged the two research and developmental focal points in the area of molecular tissue engineering as well as in the field of drug discovery and functional protein characterisation using cell and tissue based multi-electrode arrays by two further research columns in nanobiotechnology/nanoelectronics and laser directed manipulation and catapulting of living biological cells. One apogee was e.g. the presentation and clinical test of the first prototype of a cardiomyocyte based biosensor as a pre-diagnostic module for the AT1 autoimmune antibody directed to preeclampsia during pregnancy. The detection limit of this bioelectronic, functional micro-array for the AT1 receptor agonist angiotensin II is 10 -11M. A further focus rep-resents the nano-structuring of materials for a targeted positioning of cells and their laser directed manipulation, selection and catapulting. Therefore, a novel laser-bioelectronic platform for the manipulation and real time monitoring of gene modified neuronal precursor cells for neural regeneration has been developed and estab-lished.

Our projects are aimed at the understanding of structure and function of the complex RNA enzyme RNase P from different classes of organisms, and thus of the natural evolution of catalytic principles. The correlation of diverse functions to the recombi-nant protein and RNA components is achieved by mutational analysis, functional as-says and interaction studies both in vitro and in vivo.We were able to identify and structurally characterize a novel class of substrate binding site in cyanobacterial-type RNase P RNAs. Furthermore, permutation analysis led to the first detection of cata-lytic activity in an organellar RNA subunit. A specific screening procedure was devel-oped for the detection of additional RNase P-related proteins in vearious organisms. A bioinformatics approach led to the identification of several new RNase P proteins from A. thaliana; their functional verification by interaction studies is currently in pro-gress.

The enzyme R-3-hydroxybutyrate dehydrogenase, a member of the "short-chain" de-hydrogenase/ reductase enzyme family, was crystallized and X-ray diffraction analy-sis is carried out at the present time. Additionally some enzyme variants were pro-duced by site-directed mutagenesis to characterize the substrate binding region by kinetic methods.

The research group Hofmann continued the investigations on the formation of sec-ondary structures in foldamers of unnatural amino acids. The helix formation in d-peptides was a central point of the research activities. Besides, a novel type of sec-ondary structure formation in peptides was described. The formation of these so-called "mixed" helices should be possible in all homologous peptides. It is possible to favour the formation of these helices by special substituent patterns. Numerous fur-ther research activities resulted from collaborations with various other groups of the Sonderforschungsbereich 610 "Protein States of Medicinal and Cellular Relevance".

Using rational design a new variant of exonuclease III could be generated, showing an increase in the temperature optimum and a simplified production protocol. In Co-operation with the BBZ protein crystals could be grown for two thermostable proteins homologous to exonuclease. A procedure for the screening of large libraries of en-zyme variants was enhanced and for the application to various enzyme classes adapted.

Institute of Biology I

In the Department of General and Applied Botany (Prof. Dr. W. Reisser) main research activities centered on the taxonomy and ecophysiology of aeroterrestrial algae with main focus on applied aspects such as the application of aeroterrestrial algae to biomonitoring tasks.

Projects are:

  • Screening of aeroterrestrial algae for the excretion of substances with antiviral, antibacterial and/or antifungal activities,
  • Study of the role of aeroterrestrial green and bluegreen algae in the formation of soil crusts in arid aereas of Southern Africa (BIOLOG: BIOTA-South),
  • Collection of data on green and bluegreen aeroterrestrial algae to build up a databank on aeroterrestrial algae (BIOLOG: AlgaTerra).

The Department of Plant Physiology (Prof. Dr. C. Wilhelm) runs a DFG-project whose aim is the development of single cell techniques in plant biology. This open the perspective to detect the physiological state of single cells not only in suspension but also in tissues. The studies of the molecular interaction between photosynthetic pigments with proteins and lipids to regulate the photosynthetic efficiency in plants have been continued. The genes of the involved enzymes from plants of different taxonomic positions will be cloned and sequenced. A second DFG project on the efficiency of primary production under the conditions of dynamic light regimes has been started. A project entitled "in-situ hybridisation as a new tool in water quality control" has been started in the frame of the EU Marie-Curie Host Mobility Programme. The aim of this project is to identify cells and to characterise specific gene expression in single cells. The BMBF-network "thermoluminescence as a new tool for plant screening" has been finished. In cooperation with Fischer Analysen Instruments (Leipzig) a new instrument for thermoluminescence measurements has been designed and will be commercialised in next future. In a cooperation project with the Umweltforschungszentrum Leipzig/Halle Section Water ecology new methods of phytoplankton analysis and primary production assessment were test to increase the potential of water quality control technologies. In this context a water quality programme is running for lake Auensee in Leipzig in cooperation with the local administration. In a joint project with the Bundesanstalt für Gewässerkunde a new photosynthesis module for the water quality assessment modelling was developed. A new project was started to measure carbon/nitrogen, carbon/phosphorus and carbon/silica ratios in single cells by means of FT-IR microscopy. In cooperation with the departments of Prof. Buscot, Prof. Reißer, Prof. Eger, Prof. Schlegel) and the Environmental Research Centre Leipzig (UfZ Leipzig-Halle) a network was built up to analyse the function of the micorbial biodiversity on plant growth. A proposal for a DFG Research Training Group was submitted.

In the Department of Systematic Botany and Botanical Garden (Prof. Dr. W. Morawetz) the research was mainly focused on tropical ecology in South America and Australia and on systematics of tropical woody plants and primitive angiosperms (especially genus Guatteria, Annonaceae). The so-called "Surumoni project" (canopy crane site in a lowland rainforest of southern Venezuela) was continued and the analysis of the data is still going on. The basic question of the project is: How does the rainforest function? The studies comprise among others phenology, reproductive ecology and animal-plant interactions. The field studies were accompanied by computer simulation models and phytogeographic analyses as theoretical background.

Besides of this pure research on ecology in the tropics especially within the frame of the integrated project "Mata Atlântica" in Brazil studies were carried out on applied aspects of tropical vegetation and landscape ecology.

The regional research in the northwest of Saxony concentrated on biodiversity, ecology, phytosociological studies and distribution of seed plants and fungi. In this respect the greatest significance has the ecological research on woody plants and fungi in the canopy of the flood-plain forest in Leipzig ("LAK - Leipzig Canopy Crane Project").

The associated Botanical Garden was recently reconstructed and the plant collections have been enlarged systematically. Particular noteworthy and of importance for the research are the collections of tropical woody plants, ant plants, palms (Arecaceae) and Berberidaceae.

At the Department for Terrestrial Ecology (Prof. Dr. F. Buscot) research focuses on mycorrhiza and soil fungi under using of molecular and physiological techniques. Besides empiric field investigations, we perform experiments on laboratory models and in the field. Whole research activity is supported by external financed projects.

In the graduate school "function and regeneration analysis of disturbed ecosystems (University of Jena) and in the BIOLOG program granted by the federal ministry of research and education "influence of biodiversity on ecosystem processes in grasslands" (DIVA), we analysed the influence of disturbances or land use strategies on diversity of mycorrhizal communities. Using a canonical correspondence analysis, we could define the hierarchical effect of different environmental variables. A tracer experiment 15N enabled to investigate the role of mycorrhizal fungi for nutrient transfers in vegetation. In the frame of the DFG research unit "role of biodiversity for element cycling and trophic interactions" we just acquired a new project.

In our DFG project "influence of laccase production by fungi and mycorrhiza on formation and stability of organic matter, in agricultural and forest soils" in the frame of the DFG priority program SPP 1090, works on profiling diversity and expression of fungal genes encoding laccases were carried on. Seasonal variations were in the centre of the investigations this year.

Within the DFG priority program SPP 1084 we continued our project to enlighten the molecular mechanisms in the interactions between the ectomycorrhizal fungus Piloderma croceum and micro-propagated oak plants. In cooperation with the INRA at Nancy (France) we used an EST bank to develop a macro array. With this system we showed, that at the very beginning of the symbiose, plant genes up regulated encode for proteins related to stress, signal transduction and growth.

In 2004 we initiated new cooperation: one with the University of Darmstadt on interactions between members of the soil mesofauna and fungi, the other with the University of Krakow (Poland) on arbuscular mycorrhizas at zinc polluted sites.

In the workgrooup of Prof. Dr. K.-H. Gelhaar (Didactics of Biology) the main study was carried out at four high schools (N=373). It was based on the study results about ontogenesis of interest in biology among students in grades 5-10 (DFG Project of the Universities of Gießen and Leipzig) and a preliminary study (N=192) about the state of development of interest in biology in basic and advanced biology courses in years 11 and 12. Analysis of the data revealed some interesting results concerning the correlation between choice of courses, career and university and the interests of the 11th and 12th grade students.

Institute of Pharmacy

Pharmaceutical chemistry at the Institute of Pharmacy focuses on syntheses in connection with structure-activity relationships (Eger, Briel) as well as on the quality control of pharmaceutical substances.

Two projects by Prof. Eger were conducted within the centre of excellence Chemical Signal and Biological Answer, which started in 1996 and ended in 2001, but were continued in the following years. They included the search for non-toxic and easily available inhibitors of protein phosphatases, as well as adenosine receptor antagonists. The latter project included the preparative transformation of in vitro active antagonists into those with improved bioavailability. We have now succeeded in synthesising A1 and A3 antagonists of adenosinreceptors with high affinity.

Another project conducted as part of the research training group Mechanisms and Applications of Non-conventional Oxidation Reactions addresses reactions on the oxidative metabolism, the synthesis of plant components (e. g. hypericine, fagopyrine and emodine) using oxidative reactions, as well as the isolation and structural elucidation of such natural products. Drug metabolites are being prepared to be used as reference compounds for analytical purposes and haptenes.

The project with thalidomide and metabolites was continued, focusing on derivatives with stable heterocycles instead of the glutarimide ring (Eger).
Analytical investigations target the quality assurance of drugs, such as identifying impurities which result from preparative procedures. Several drugs were investigated and impurities separated, characterised spectroscopically, as well as synthesised by independent routes (by Professor Eger´s group).
Work was additionally funded by the pharmaceutical industry, as well as the German Institute of Drugs an Medical Products.

In the area of pharmaceutical technology (research group of Professor Süß) the optimization of solid oral dosage forms with controlled or modified drug release as well as the development and structural investigation of the required excipients and intermediate products, particularly by application of the sol-gel technique, are of special interest.
The research work concerning the curing of coated dosage forms as well as the development of multiparticulate systems for oral use has been continued. Additional research is focusing on the field of quality of homoeopathic formulations.

Research projects conducted by Prof. Leopold´s research group focus on technological as well as biopharmaceutical issues. One major goal is the quantification and optimisation of percutaneous drug penetration (collaboration with Prof. Howard Maibach, UCSF, San Francisco). Different ointment bases and penetration enhancers are investigated with regard to their effect on the penetration rate of selected model drugs. Penetration measurements are done noninvasively by determination of the pharmacodynamic response in vivo with suitable response parameters (funding by DAAD). The optimization of transdermal patches involves the development and characterization of novel silicon-based adhesives as drug matrix (collaboration with Jenapharm, Jena).

Physiochemical interactions between coating polymers and core components are investigated for improvement of the stability of coated dosage forms as well as the development of modified release dosage forms. Aim is a delayed or pulsatile drug delivery as required for colon-specific drug delivery. Under certain conditions even a sustained drug release is observed, which can be useful in the design of dosage forms for once daily administration (collaboration with Apogepha, Dresden).

A BMBF project (IKON) deals with the investigation of alternative sterilization processes based on a pressure change technolgy.

Further projects involve the development of dosage forms for loess (healing earth), which acts as an adsorptive material for internal as well as external use. Dosage forms are tablets as well as dry and moist face-masks (collaboration with Heilerdegesellschaft Luvos Just, Friedrichsdorf).

The Pharmacology for Natural Sciences (Prof. Karen Nieber) specialises in electrophysiological investigations (intracellular recordings, patch-clamp-setup, Ca2+-imaging) on cortical pyramidal cells. Research topics include new singualling pathways of the adenosine-A3-receptor and the mode of action of ampakines ion cortical neurons. Nieber´s group is further intrested in the role of adenosine A3-receptor during hypoxia. These studies (in cooperation with K. Eger´s group) are supported by the DFG; project "Presynaptic adenosine A3-receptors on cortical neurons: Neuroprotective targets during hypoxia". In a further study we evaluate the adenosine A1-receptor-mediated effect of a valerian extract. The valerian extract inhibits the synaptic transmission by activating of adenosine A1 receptors (Collaborations with Prof. C. Müller, Bonn and Zeller AG, Swizerland).

A second area of investigation deals with the effect of adenosine receptor ligands on the inflammatory processes on the rat ileum. It is succeeded to establish on in vitro model to test adenosine A2A-receptor mediated antiinflammatory effects (collaboration with Prof. C. Müller, University of Bonn). In cooperation with the Department of Immunobiology (Prof. S. Hauschildt), signalling pathways are being studied on human monocytes / macrophages. The results indicate new effects of intracellulary applied LPS and extracellulary acting NAD+.

One major goal further projects in cooperation with the IZKF Neuroimmunological Cell Biology unit, is the identification of binding proteins and receptors for advanced glycation endproducts (AGEs). Additionally, there role was studied in a hyperclycemia model.

Numerous cooperation agreements exist with other national and international research laboratories.

Institute of Biology-II

The research at Institute of Biology-II covers a wide range of topics including genetics, cell biology, immunobiology, neurobiology, systematics, and ecology. The research focus of some of the departments are summarized below:

The Department of Immunbiology (Prof. S. Hauschildt) aims at the production of monoclonal antibodies against a variety of antigens (vitellin-antibodies in chicken; moenomycin in mice). Additionally the research deals with basic questions in cell biology, e.g. mechanisms of apoptosis, activation of human macrophages, and signal transduction in human monocytes.

The Department of Molecular Evolution and Animal Systematics (Prof. M. Schlegel) uses advanced methods from molecular biology to investigate the genealogical relation between groups of animals (e.g. Myxozoa, Hemichrodata, Isopoda). Another line of research is the geneflux analysis in natural populations of molluscs and coleoptera. Various methods are used depending on the scope of the projects, i.e. cloning and sequencing of different genomic regions with the LICOR equipment, microsatellite and RAPD fingerprinting and allozyme electrophoreses.

The research in the Department of General Zoology and Neurobiology (Prof. R. Rübsamen) and in the Department Animal- and Behavioral Physiology (Prof. K. Schildberger) focuses on mechanisms of information processing in the central nervous system. By applying a broad variety of advanced neurobiological methods, one focus of research is information processing in the central auditory system of mammals (including humans) and insects. Additionally the neuronal control of aggressive behavior in insects is studied.

Work group of Developmental Neurobiology (Prof. W. Naumann) investigates the evolutionary origin of radial glial cells and the influence these cells have on the differentiation of the nervous system in vertebrates and invertebrates.
The work group Humanbiologie (Prof. G. Poeggel) studies the influence of adverse emotional experience like prenatal stress or early postnatal deprivation on the development of central nervous transmitter systems as a model for experience-dependent modifications of the chemoarchitecture of the brain. The reserach focuses on dopaminergic and serotonergic subsystems in the Amygdala.

Work in Professor H. Sass' research group in the Department of Genetics is aimed at: 1. Identification and understanding the genes and gene regulatory components of the Drosophila genome. Among the genes studied are the intron/exon structure evolution and evolutionary changes of the functionally unrelated Su(var)3-9/eIF2γ gene fusion, and klett (dip 1)gene expression. We are also analyzing molecular mechanisms that govern chromatin specification including SU(VAR)3-9 histonmethyltransferase and chromosomal protein KLETT (DIP 1). 2. The gene ontology project ‚Forms of Life' is a interdisciplinary collaboration under the guidance of the philosopher Prof. B, Smith (IFOMIS, Saarland University) together with Prof. H. Sass (Department of Genetics) and Prof. P. Stekeler-Weithofer (Institute of Philosophy), both University of Leipzig. This Relation Ontology project (sponsored by the Volkswagen Foundation) is directed to develop coherently defined relations (‚controlled vocabularies' in bioinformatics) in biological and biomedical ontologies. The resulting Relation Ontology has implications for ontology construction in the life sciences generally and helps to improve reasoning about biological phenomena.

All Departments of the Institute of Biology-II are actively engaged in many regional, national, and international scientific cooperations, among which are the Umweltforschungszentrum Leipzig-Halle, the Sächsische Institut für angewandte Biotechnologie (SIAB), and the Interdisziplinären Zentrum für Biotechnologie (IZBI). Researchers at the Institute contribute to the DFG-Schwerpunktprogramm "xxx", the DAAD-Promotionskolleg "Von der Signalverarbeitung zum Verhalten", the DFG-Graduiertenkolleg "Interneuro", the DFG-Graduiertenkolleg "The function of attention in Cognition" und to the Max-Planck Research School "Human Origin".

Institute of Psychology I

In cognitive including biological psychology (Prof. Dr. E. Schröger), studies were carried out into auditory and audio-visual information processing concerned with interlinked issues in the areas of perception, memory and attention.

In General Psychology and Methods of Psychology (Prof. Dr. M. M. Müller) research was mainly focussed on attentional processes and the role of gamma-band activity in the electroencephalogram.

In the psychology of cognition, higher cognitive functions (Prof. Dr. J. D. Jescheniak) work on language production was carried out.

In cognitive social psychology (Prof. Dr. G. von Collani), research was carried out into the measurement and validation of socio-psychological personality constructs, the biasing of eye witness testimonies, hindsight bias, models of attitude-behaviour relationship, measuring implicit attitudes using reaction-time procedures, and measuring stereotypes and prejudice (constructs of 'Social Dominance Orientation', 'Ambivalent Sexism').
Research at the Institute was supported by a number of DFG project grants. The Institute is equipped with modern laboratories for EEG recording as well as other special laboratories. The research activities of the various work groups are closely interconnected. Numerous co-operation agreements with other national and international research laboratories exist, especially with the MPI of Cognitive Neuroscience in Leipzig.

Institute of Psychology II

Research by the Department of Work- and Organizational Psychology (Prof. G. Mohr) addressed various research topics in 2004: leadership and gender context, leadership and emotion, perception of leadership by followers etc. The Department is also involved in establishing an instrument for the assessment of irritation at the workplace. As a member of an international research group in cooperation with Stockholm (Sweden), Gent (Belgium), Jerusalem (Israel), London (United Kingdom), Tilburg (Netherlands) and Valencia (Spain) a study about contract at the workplace was started (PSYCONES - Psychological Contracts across Employment situations). Also a study continued with alumni of the Institutes of Psychology of the University of Leipzig.

In the Clinical and Health Psychology Department (Prof. Dr. H. Schröder) specific stages of research dealing with coping with stress, health analysis and health promotion in organisations, medical rehabilitation and Adjustment Disorders were completed. We also completed health-psychological projects with orchestral musicians as well as nurses, who work in hospices, palliativ-medicine hospitals and nursing homes. We evaluated and improved our programs in psychosocial intervention of stage-fright, stress regulation, and psychotherapy with trauma patients. We are presently involved in international projects dealing with the relationship between coping with demands and health status in the context of macro social transition (EU-extension) and evaluation of psychotherapeutic processes.

At the Department of Personality Psychology and Psychological Intervention (Prof. H. Petermann), the following research project was undertaken in 2004:

Evaluation of a drug prevention program of Lions-Quest in Germany (sponsored by SMK Saxony, SMS Saxony, Leipzig Public Health Department, Leipzig Regional Schools Department, German Lions relief organisation)

In 2004 the main attention of the Educational Psychology unit (Prof. Dr. Witruk) was again concentrated on the experimental exploration of basic functions of reading and developmental reading disability. In collaboration with the University of Helsinki a study on etiological subgroups in dyslexia (in collaboration with the University of Helsinki) was completed successfully. An experimental series on perceptual strategies in letter recognition was effectively preceded in collaboration with the Brain Science Institute, Tokyo. With support of further grants, research projects on cross-cultural effects in visual perception in collaboration with the University of Tasmania (Australia), working memory in collaboration with the HongKong University of China and on violence in school contexts of Bahir Dart (Äthiopien) were conducted. The interest on media psychology was further heightened. A helpdesk for partial developmental disorders was established.

 

 

 

Home Zusammenstellung: Forschungskontaktstelle, 17.10.2005