Faculty of Biosciences, Pharmacy and Psychology

Research Activities at the Faculty

Institute of Biochemistry

In 2006 the Institute of Biochemistry has strengthened its research areas peptide hormones, RNAses, molecular modelling, metabolic biochemistry of anaerobic microorganisms, white biotechnology as well as nanobiotechnology. The institute has focused its inter- and transdisciplinarity with the new head of the division of metabolic biochemistry, Matthias Boll, and has established a further focus in industrial biotechnology under the supervision of Wolfgang Zimmermann. This research area was promoted by the independent InnoProfile junior research group funded by the Federal Ministry of Research and Technology and headed by Thomas Greiner-Stöffele. In 2006 the group of Andrea Robitzki could realize a further great technological effort in the field of semiconductor technology whereas a new semiconductor clean room of the class 10/100 could be established for novel fabrication processes as well as first micro-structures in the field of micro-implants and medical micro devices (biosensors). In the field of structure-activity relationships of peptide hormones the group of Annette Beck-Sickinger was very successful in 2006 in identifying a calcitonin gene related peptide (CGRP) antagonist with pico-molar affinity. CGRP is one of the major inducers of migraine. Furthermore, significant advances to identify structure activity relationships of orexin and ghrelin – both involved in the regulation of food intake have been performed.

In the field of structure-activity relationships of peptide hormones the group of Beck-Sickinger was very successful in 2006. Accordingly, the identification of a calcitonin gene related peptide (CGRP) antagonist with picomolar affinity was achieved. CGRP is one of the major inducers of migraine. Furthermore, significant advances to identify structure activity relationships of orexin and ghrelin – both involved in the regulation of food intake have been performed. In the field of carrier peptides we could achieve a significantly prolonged stability in human blood by modifying the peptide sequence. This is of major importance for their application in therapy. Significant advances were furthermore obtained in the field of G-protein coupled receptors. We could identify the essential binding sites of ghrelin and chemokine receptors. A major break-through was obtained in the field of adiponectin receptors: the orientation within the membrane was achieved by novel receptor constructs combined with new labelling strategies.

In 2006, the group of Mario Mörl succeeded in demonstrating a specific interaction of the multifunctional protein Hfq with tRNA transcripts. This is the first direct proof how this protein can stimulate the activity of tRNA nucleotidyltransferase. Furthermore, studies on structure – function relation were successfully conducted. Thereby, it was possible to characterize a variant form of the human tRNA nucleotidyltransferase resulting from an alternative splicing event of the corresponding mRNA. This represents the first splice variant of this group of enzymes. It shows a modified catalytic activity, which is a substantial contribution to the understanding of the reaction mechanism.

Additionally, the comparative study on tRNA nucleotidyltransferases and poly(A) polymerases was continued. Both enzymes show a high sequence similarity in conserved regions of the catalytic core. De obtained results indicate that poly(A) polymerase evolved out of tRNA nucleotidyltransferase and is now in a fixed structural orientation that allows exclusively the incorporation of ATP into poly(A) tails.

In the group of Hans-Jörg Hofmann the investigations of secondary structure formation in foldamers of unnatural amino acids were continued. The focus was on calculations of the helix formation in hybridpeptides consisting of two different homologous amino acids in alternate order. Besides, efficient formalisms of protein-ligand-docking were developed. Another project dealt with the influence of lithium cations on peptide bonds.
A key issue of the research activities at the group of Wolfgang Zimmermann is the identification and characterization of microbial enzymes and the development of enzyme-related technologies geared towards the introduction of novel products to industry. The focus has been on bacterial enzymes from actinomycetes and Bacillus spp. for the synthesis and modification of novel cyclodextrins (carbohydrate bioengineering) with applications in the pharmaceutical and food sectors, as well as in nanobiotechnology. The manipulation of the product specificity of bacterial glucanotransferases was studied using molecular imprinting and enzyme immobilization technologies. In the area of polymer biotechnology, the specific functionalization of synthetic polymers has been investigated and microbial enzymes with polyethylene terephthalate- and polyamide-modifying activities have been identified.

In 2006 the group of Andrea Robitzki could realize a further great technological effort in the field of semiconductor technology. By establishing a new semiconductor clean room of the class 100, novel fabrication processes as well as first micro-structures in the field of micro-implants and medical micro devices (bisensors) could be developed. A novel 3D cavity chip was fabricated and validated for real time monitoring of 3D in vitro tissue models, e.g. for an online and real time detection (bio-impedance spectroscopy) of myocard ischemia in 3D cardiomyocyes or physiological changes in 3D melanoma. This biosensor platform was successfully adapted to a microlaser manipulation platform for studying neural regeneration of e.g. dorsal root ganglion cells or for realizing the proof of principle of therapeutical concepts.

The research group of Matthias Boll is studying the physiology and biochemistry of aromatic metabolism in anaerobic bacteria. The full degradation of aromatic compounds has long been thought to be strictly dependent on molecular oxygen. However, in recent years anaerobic bacteria have been isolated which use aromatic compounds as sole source of cell carbon and energy. These bacteria contribute to a large extend to the global carbon cycle and to the bioremediation of aromatic xenobiotics released to nature.
In the anaerobic aromatic metabolism oxygen-dependent pathways have to be replaced by alternative enzymatic reactions. Many of these reactions follow unknown mechanisms, often representing new biochemical principles. Some of the discovered enzymes might be of biotechnological interest as biocatalysts for the production of fine chemicals and pharmaceuticals.

The group of Hauke Harms has developed new methods suited to attribute highly desired, microbe-based ecosystem services such as pollutant degradation to individual member species of highly diverse microbial communities. These methods rely on the one hand on the optical single cell analysis and physical separation of specifically stained organisms, followed by phylogenetic analyses. On the other hand, it has become possible to analyse proteomes of entire microbial communities for represented catabolic functions and attribute them to specific organisms by comparison with information from genome data banks. Encouraging results were obtained regarding the degradability of the priority groundwater contaminant MTBE by bacterial isolates.

The research field of the junior research group Protein Engineering of Thomas Greiner-Stöffele was the application and development of methods for the rational protein design and for in vitro evolution of proteins. In 2006 two areas were in the focus of the group. On the one hand the work on exonuclease III of E. coli and two thermostable proteins from A. fulgidus und M. thermoautotrophicus has been continued. Derived from the x-ray structure of both thermostable proteins probably stabilizing mutations were introduced in exonuclease III of E. coli. Additionally the catalytic centers of all three enzymes were analyzed using mutagenesis studies and first hints for the basis of the different specificity regarding endo- or exonucleolytic activity of these nucleases could be found.

Within a collaboration project new systems and assays for the screening of new restriction endonucleases inside genomic DNA libraries were developed. The generation of a “proof of concept” starting from a strain with an known restriction endonuclease was started.

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 growing on soil and on bark with main focus on applied aspects. Other projects dealt with the isolation of mosses and the development of techniques for mass culturing.

The Department of Plant Physiology (Prof. Dr. C. Wilhelm) continues a DFG-project whose aim is the development of single cell techniques to detect the physiological state of single cells not only in suspension but also in tissues. The perspective of such a system is to assess the primary production with taxonomic resolution. A second DFG project on the efficiency of primary production under the conditions of dynamic light regimes has been started. An experimental set-up has been established which allows to quantify the metabolic costs during growth. This method is now used to identify growth limiting reactions under extremophilic conditions e.g. as in acidic lakes with a pH of 2,0. A project entitled „in-situ hybridisation as a new tool in water quality control“ has been continued as a part 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 methodology of “thermoluminescence as a new tool for plant screening“ is now in progress to become commercialised in cooperation with Fischer Analysen Instruments (Leipzig). The applicability of the method has been extended to measure oxidative stress also in animal or human tissues and is funded by the innovation initiative ProInnoII. A BMBF funded joint project with the Bundesanstalt für Gewässerkunde and the Fraunhofer Institute in Stuttgart project was started to measure carbon/nitrogen, carbon/phosphorus and carbon/silica ratios in single cells by means of FT-IR microscopy. The coordination of this network is in the responsibility of Prof. Wilhelm at the University of Leipzig. Research groups from different universities and research institutions have started a cooperative research on the primary metabolism of Diatoms. The group is coordinated by Prof Wilhelm (Leipzig) and Prof. Kroth (Konstanz) including the following partners: Prof. Büchel (Universität Frankfurt; Dr. Lohr Universität Mainz, Prof. Kroth, Prof. Lavaud, both Universität Konstanz, Prof. LaRoche und Prof. Riebesell, beide Universität Kiel, PD Fiesahn, MPI Golm and Dr. Valentin, Alfred Wegener Institut). Shared research projects on thylakoid membrane biochemistry and biophysics were run between the Jagiellonian University (Krakau) und the University of Szeged and has been funded by the DAAD. A cooperative research on toxic algae has been started with the University of Ancona (Prof. Giordano). The aim of the programm is shared PhD work on the physiological regulation of toxin production by means of FT-IR spectroscopy.

In the Department of Systematic Botany, Botanical Garden and Herbarium (Prof. Dr. W. Morawetz) the research was mainly focused on tropical ecology in South America and Australia and on systematics of tropical, mainly woody plants (e.g. Annonaceae, Malvaceae, Marcgraviaceae, Quiinaceae). The so-called "Surumoni project" (canopy crane site in a lowland rainforest of southern Venezuela) was continued. 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 projects „Mata Atlântica“ and “Emerging Megacities” in Brazil studies were carried out on applied aspects of tropical vegetation and landscape ecology.
The regional research was concentrated on woody plants, fungi and slime molds in the canopy of the flood-plain forest in Leipzig ("LAK - Leipzig Canopy Crane Project").
The associated Botanical Garden is integrated in the research in many respects. Its plant collections have been enlarged systematically. Particular noteworthy are the collections of tropical woody plants, palms (Arecaceae) and Berberidaceae and Gesneriaceae as well as the diversity garden displaying representatives of all recent vascular plant families.
The workgrooup of Prof. Dr. C. Randler (Didactics of Biology) focuses on teaching and learning in the subject biology in secondary schools. Main aspects are empirical evaluations of teaching methods, development and implementation of new curricula/syllabi and out-of school learning environments.

Institute of Pharmacy

Pharmaceutical chemistry at the Institute of Pharmacy focuses on syntheses (Eger, Briel) as well as on the quality control of pharmaceutical substances.

Three projects by Prof. Briel specialises in syntheses in connection with structure-activity relationships. They included the search for new A2 antagonists of adenosine-receptors, novel anticonvulsant compounds and development of low-molecular inhibitors of proteases and esterases. 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 nstitute of Drugs an Medical Products.

The Pharmacology for Natural Sciences (Prof. Dr. Karen Nieber) specializes in electrophysiological investigations (intracellular recordings, patch-clamp-setup, Ca2+-imaging) on cortical neurons and neuronal cell lines. Research topics include new signalling pathways, desensitization mechanisms and receptor interactions of adenosine A1- and A3-receptors during hypoxia. New receptor ligands have been tested on brain slice preparations or cell lines (in cooperation with Prof. C. Müller, Institute of Pharmacy, Bonn and Prof. Beck-Sickinger, Institute of Biochemistry, Leipzig). These studies are partly 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 valerian extracts (in cooperation with Prof. Brattström, Zeller AG, Swizerland).

A second area of investigations deals with effects of adenosine receptor ligands on inflammatory processes on the rat ileum. Pharmacological, molecularbiological and histological investigations have been done. In cooperation with Steigerwald GmbH plant extracts have been tested to influence the inflammatory processes. We evaluate the involvement of adenosine receptors in the mode of action of these plant extracts.
Our group is involved in an network project “Biocompatibility of synthetic materials for implants” together with the Kunststoff-Zentrum in Leipzig gGmbH, KET Kunststoff- and Elasttechnik GmbH Liegau and the group of Prof. Hauschildt (Institute of Biology II). This project is sponsored by the Technologieförderung with 75 % EU portion (EFRE-project). It deals with the structural and surface compatibility between urethane and silicon materials and human cells.

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

Pharmaceutical Technology

Research activities of the department of pharmaceutical technology focus on bone tissue engineering. We approach the subject from three perspectives: The development and processing of biomaterials into three-dimensional scaffolds, the development of controlled release systems for growth factors, and the investigation of growth factor effects on bone regeneration with 2- and 3-dimensional test systems based on bone marrow stromal cells.
Our sponge-like scaffolds are made of biodegradable polymers. They show excellent pore sizes to address the problem of nutrient gradients forming over the cell loaded three-dimensional scaffolds to tackle the problem of gradients within the scaffolds. This issue is also addressed in cooperation with the department of pharmaceutical technology, University La Laguna, Tenerife, Spain.

Bone marrow is al lifelong reservoir for stem cells including mesenchymal stem cells (MSC). MSC are able to differentiate into different connective tissue-forming cells. They represent the cellular component of our test system for growth factor effects. Marrow stromal cells are additional investigated concerning their integrin expression and their interactions with other bone marrow cells aiming at selective adhesion of bone forming cells in presence of interfering hematopoietic cell.

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 working group Molecular Evolution and Animal Systematics (Prof. M. Schlegel) investigates (i) phylogeny of heterotrophic protists (predominantly ciliates) and their biodiversity in different ecosystems (e.g. constructed wetlands; (ii) basal ramification of Deuterostonia in the Cambrian Radiation; (iii) the historical and spatial impact on genetic variation of animal populations including the recent impact of climate change; (iv) phylogeography of selected arthropod taxa, e. g. arcto-alpine distribution patterns of spiders. On the higher taxonomic level we analyse besides morphological characters ribosomal RNA gene sequences, rRNA secondary structure, evolution of the mitochondrial genome, and the histone gene-cluster. At the population level we use rapidly evolving mitochondrial DNA segments and microsatellites.

The Department of Immunobiology (Prof. S. Hauschildt) is studying molecular mechanisms underlying the activation of human monocytes/marcrophages by lipopolysaccharides. The aim is to define mechanisms that can be used as therapeutical targets in pathophysiological situations. One research topic focuses on the effect of extracellular nucleotides (NAD+) on biologic answers of the cells. Immunological-, molecular biological and electrophysiological methods are applied. By the use of these methods, properties and functions of proteins (ARTs) will be defined, that are involved in the action of NAD+.
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 research focuses on dopaminergic and serotonergic subsystems in the Amygdala.

Research topics in the work group Genetic (Prof. H. Sass) are:

• Functional studies of gene regions from Disco Interacting Protein [DIP1] and a gene we have identified in Leipzig 2006, called female sterile 1(20A) [fs(1)20A]
• Evolution of heterochromatic histone H3K9 methyltransferases
• Quantity and distribution of methylated DNA in hemimetabolic insects
• The phylogenetic usage of intron positions
• Forms of life - Philosophical dimensions of contemporary biomedical research
• Identification of novel genes from Drosophila melanogaster via 5’ gene trapping by hsp82-neo trap-vectors pHS155 (Sass, H. 2006) and pHS160

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 „Zeitgebundene Informationsverarbeitung im zentralen auditorischen System“, 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 General Psychology and Methods of Psychology (Prof. Dr. M. M. Müller) research was mainly focussed on attentional processes and cortical networks.
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 the Psychology of Cognition, Higher Cognitive Functions (Prof. Dr. J. D. Jescheniak) work on cognitive aspects of language processing was carried out focussing on semantic, syntactic and phonological processes during language production.

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 for Human Cognitive and Brain Sciences.

Institute of Psychology II

The Department of Work- and Organizational Psychology (Prof. G. Mohr) pursued various research topics in 2006: leadership and gender context, leadership and emotion, experiencing non-paid work, irritation, job insecurity, willingness to be mobile. Data of an international research project, in cooperation with Stockholm (Sweden), Gent (Belgium), Ramat Gan (Israel), London (United Kingdom), Tilburg (Netherlands) and Valencia (Spain), concerning the psychological contract at the workplace were further analyzed (PSYCONES - Psychological Contracts across Employment situations). In addition, work continued on a study of the alumni of the Institutes of Psychology at the University of Leipzig.

The Clinical and Health Psychology Department (Prof. Dr. H. Schröder) proceeded with research on topics concerning coping with stress, health analysis and health promotion in organizations, medical rehabilitation and Adjustment Disorders. We expanded on studies dealing with psychosocial support and with compliance of children with cancer, and completed health-psychological projects focusing on orchestral musicians, and nurses working in hospices, palliative-care hospitals and nursing homes. We evaluated and improved on our psychosocial intervention programs dealing with stress regulation, coping with adjustment disorders, and psychotherapy with trauma patients. Work continued on international projects addressing the relationship between coping with demands and health status in the context of macrosocial transition (EU-extension). Further evaluations of psychotherapeutic processes took place.

In 2006, the Educational and Rehabilitative Psychology unit (Prof. Dr. E. Witruk) focussed on experimental studies dealing with the basic functions of reading and picture processing, as well as on developmental reading disability. With the support of further grants, research projects in collaboration with the University of Tasmania (Australia) on cross-cultural effects in visual perception, and projects in collaboration with the Hong Kong University of China and with Moroccan schools on working memory were conducted. The research on media psychology and on intervention methods for teachers was further intensified. Investigations began concerning adjustment and stress disorders after natural disasters, with special emphasis on tsunamis.

In 2006, the following research projects were carried out by members of the unit Personality Psychology and Psychological Assessment (Prof. Dr. B. Egloff):

• Indirect assessment of personality dispositions (supported by DFG)
• Emotion regulation
• Individual differences in experiencing and remembering emotional events
• Spontaneous interpersonal attraction and personality

At the Department of Personality Psychology and Psychological Intervention (Prof. H. Petermann), the following research projects were undertaken in 2006:

• Sensation seeking based on need theory
• World-view and religiousness. Contents of personal religious beliefs
• Validation of personality types