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.
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