|
Eleven groups participate in this doctorate program which are concerned
with various aspects of biochemical, cell biological and biomedical
research. In particular these groups are:
Ludwig
Maximilians-Universität München, Fakultät
für Medizin
|
|
|
Prof. Dr.med.
Dr.rer.nat. Walter Neupert
Adolf-Butenandt-Institut
für Physiologische Chemie der Universität
München,
Butenandtstr. 5,
81377 München,
Germany
Tel.:
089-2180-77094/95,
Fax: 089-2180-77093
This e-mail address is being protected from spambots. You need JavaScript enabled to view it
http://pluto.heiss.org/ipcv1/index.php?option=com_content&task=view&id=15&Itemid=83
|
|
Research Interests:
Molecular
characterization of mitochondrial protein translocases and
morphogenesis:
There are six translocase machineries known which are responsible for
the import and sorting of precursor proteins into
mitochondria. These are the TOM and the TOB complex in the
outer membrane (Group Rapaport), the Mia40-Erv1 disulfide
relay system in the intermembrane space, the TIM23 complex
(Group Hell), the TIM22 complex (Group Hell) and the OXA1 complex
(Group Herrmann) in the inner
membrane.
With the help of these supramolecular complexes proteins are
transported into four different mitochondrial
subcompartments: the outer membrane, the intermembrane space, the
inner membrane, and the matrix. Our lab contributed
substantially towards an understanding of the molecular
composition and function of these translocase complexes. For that,
baker's yeast (Saccharomyces cerevisiae) and Neurospora
crassa are mainly used as model
organisms.
In general, the individual groups of our lab deal with the molecular
composition of each of these translocase machineries, with
the mechanism of membrane crossing and insertion, and with
the interaction of these complexes with each other.
Furthermore, we focus on basic aspects of morphogenesis and
the structural organization of mitochondria (Group
Reichert).
With the determination of the mitochondrial proteoms of yeast,
Neurospora crassa and human we want to improve our
understanding of mitochondrial function and determine its
physiological importance for human disease.
Furthermore, we are interested in gaining a deeper understanding of
molecular machines by determining their 3D-structures (Group
Groll).
|
| |
|
| |
|
Prof.
Dr. Peter B. Becker
Adolf-Butenandt-Institut der Universität München,
Abteilung für Molekularbiologie,
Schillerstr. 44,
80336 München,
Germany
Tel: 089-5996-427/428,
Fax: 089-5996-425
This e-mail address is being protected from spambots. You need JavaScript enabled to view it
http://www.molekularbiologie.abi.med.uni-muenchen.de/ueber_uns/becker/index.html
|
|
Research Interests:
Research in the Becker lab focuses on the molecular mechanisms by which
modulators of chromatin structure regulate the activity of
chromosomal loci. We strive to understand the principles that
govern the targeting of regulators to specific chromatin loci, the
nature of the structural changes provoked by these factors,
as well as the molecular mechanisms through which alterations
of chromatin structure affect enzymes involved in nucleic acid
metabolism. We are interested in the mechanism and regulation
of ATP-dependent nucleosome remodeling by the ISWI containing
CHRomatin Accessibility Complex (CHRAC) and its functional significance
in vivo. A second broad theme is to
understand the principles that underlie the process of dosage
compensation in Drosophila, which involves enhancing the transcription
of the majority of genes on the single X male chromosome by
two-fold. The acetylation of histone H4 at lysine 16 by the
acetylase MOF is causally involved in this increased transcription. MOF
is targeted to the X chromosome as part of a dosage
compensation complex consisting of several ‘male-specific
lethal’ proteins and non-coding roX RNA. Using a
variety of biochemical, cell biological and genetic methods
we are characterising the molecular interactions that define the dosage
compensation complex and its association with X chromosomal
chromatin.
|
| |
|
| |
|
Prof.
Dr. Christian Haass
Adolf-Butenandt-Institut der Universität München,
Abteilung für Stoffwechselbiologe,
Schillerstr. 44,
80336 München,
Germany
Tel.: 089-5996-471/472,
Fax: 089-5996-415
This e-mail address is being protected from spambots. You need JavaScript enabled to view it
http://haass.web.med.uni-muenchen.de/
|
|
Research Interests:
In the 'Laboratory of Alzheimer's and Parkinson's Disease Research' we
study pathogenic processes, which lead to neurodegenerative dieseases.
We focus on the generation of a deadly peptide, the Amyloid
ß-peptide (Aß), which accumulates during aging in
our brains, and becomes deposited as insoluble aggregates called
amyloid plaques. Since Aß has a central role in AD pathology,
we investigated the mechanisms behind its generation. It quickly became
clear that Aß is generated by proteolytic processing
involving two types of proteases, ß-, and
γ-secretase. Both secretases are major drug targets, since
their inhibition should slow down the age related neuropathology caused
by aggregating Aß.
Our work on γ-secretase focuses on its identification,
function, assembly, and reconstitution. By identifying the active sites
of the γ-secretase activity in presenilins, we were able to
define a completely novel class of aspartyl proteases. By using C.
elegans and zebrafish as a model system in combination with biochemical
and cell biological technologies, we could demonstrate that presenilins
not only play a role in Aß generation but are also directly
involved in the Notch signaling pathway, which is important in
development of higher organisms. However, Presinilins alone could not
perform proteolysis and we could demonstrate that a complex composed of
four different proteins is required to reconstitute
γ-secretase activity in yeast . Currently we are
investigating the assembly of the γ-secretase complex and the
interaction sites of the individual components. Similar complexes
involved in analogous signaling pathways are functionally investigated
in the zebrafish model. In addition we are searching for mechanisms,
which could affect the precision of the γ-secretase cleavage
during aging and thus lead to enhanced aggregation and deposition of
Aß.
In parallel we are studying the function and regulation of
ß-secretase. Here we are specifically interested in
regulative mechanisms, which may be responsible for the increased
ß-secretase activity during aging. First evidence suggests a
posttranscriptional mechanism via the 5' untranslated region of the
ß-secretase mRNA. The function of ß-secretase and
its homologues is investigated in zebrafish.
Zebrafish is also used to generate a vertebrate model system for the
investigation of age related Aß neurotoxicity. Based on such
a model we currently prepare a mutagenesis screen to identify enhancers
and inhibitors of Aß mediated cell death in vivo.
Our work on the molecular mechanisms of AD pathology is complemented by
the investigation of similar age dependent diseases such as Parkinson's
disease (PD) and Prion disorders. Transgenic mouse models for PD
pathology have been generated and are currently used to identify small
compounds, which are able to prevent α-synuclein mediated
neuropathology. The pathological and biological function of genes
associated with early onset PD is investigated in zebrafish.
The 'Laboratory of Alzheimer's and Parkinson's Disease Research' uses a
wide range of biochemical and molecular biological methods as well as
standard and confocal microscopy to analyze our cell culture and in
vivo models of neurodegenerative diseases.
|
| |
|
|
|
Prof. Dr. Manfred Schliwa
Adolf-Butenandt-Institut der Universität München,
Abteilung für Zellbiologie,
Schillerstr. 42,
80336 München,
Germany
Tel.: 089-5996-884/4,
Fax: 089-5996-882
This e-mail address is being protected from spambots. You need JavaScript enabled to view it
http://zellbio.web.med.uni-muenchen.de/
|
|
Research Interests:
Our group is interested in the molecular und cellular properties of the
motor protein Kinesin.
Molecular motors are a force-generating enzymes which convert the free
energy of the phosphate bond of ATP into mechanical work.
This work is used to power the transport of intracellular organelles
along microtubules. The development of in vitro motility
assays for studying motors has yielded new insights into the
mechanical workings of motor proteins.
Kinesin - driven motility can be directly monitored in cell-free assays
by observing, under the microscope, the gliding of individual
fluorescently marked microtubules across glass surfaces
coated with purified kinesin. By using a TIRF microscope, we can also
visualize single fluorescently labeled kinesin motors and
analyze their motility. We are able to observe single
fluorophores moving along microtubules and measure their velocity and
run length.
Another focus of our research is the centrosome of Dictyostelium
discoideum. PD. Dr. Ralph Gräf
developed a method to purify centrosomes free of microtubules in our
lab. Additionally, we adapted Tandem Affinity Purification
for this organism to find centrosomal and microtubule
associated protein interactors.
In summary, our scientific expertise includes:
- Microtubule-dependent intracellular
motility
- Protein biochemistry of cytoskeletal
proteins
- Kinesin motor proteins
- Confocal microscopy
- TIRF microscopy
- In vitro motility assays
- Multiple-motor assays
- Single-motor assays based on fluorescently
labeled motors
- In vivo motility in Neurospora crassa and
Dictyostelium discoideum
- Steady state and pre-steady state kinetics of the
kinesin-microtubule ATPase
|
| |
|
| |
|
Prof. Dr. Michael
Schleicher
Adolf-Butenandt-Institut der Universität München,
Abteilung für Zellbiologie,
Schillerstr. 42,
80366 München,
Germany
Tel.: 089-2180-75876;
Fax: 089-2180-75004
This e-mail address is being protected from spambots. You need JavaScript enabled to view it
http://zellbio.web.med.uni-muenchen.de/
|
|
Research
Interests:
The molecules that are involved in the actin cytoskeleton remodelling
are the focus of our group. Dynamic actin cytoskeleton is a key member
of cell migration, which is the basis of processes ranging from cell
division to development. To get an insight into the actin dynamics we
characterize the role of actin-binding and regulating proteins like
formins and Ste20- like kinases respectively. A combination of cell
biology (gene knock-out), biochemistry (in vitro actin polymerization)
and microscopy (confocal, Reflection Interference Contrast Microscope
–RICM and Total Internal Reflection Fluorescence
–TIRF) techniques are primarily used as tools in our
research. Dictyostelium discoideum is the model system we use for the
study as this simple haploid organism allows us to investigate cell
motility at the single cell and multicellular stage with biochemical
and molecular methods.
|
| |
|
Ludwig
Maximilians-Universität München, Fakultät
für Biologie
|
|
|
Prof. Dr. Jürgen Soll
Institut für Botanik,
Menzingerstr. 68,
80638 München
Tel.: 089-17861-244/245
Fax: 089-17861-185
This e-mail address is being protected from spambots. You need JavaScript enabled to view it
http://www.botanik.bio.lmu.de/professuren/soll/index.html
|
| |
Research Interests:
Protein transport processes of
chloroplasts
Research in the group of Prof. Dr. J. Soll focuses on transport
processes across the two envelope membranes of
chloroplasts.
The first aspect concerns the posttranslational import of preproteins
and characterized several subunits of the Toc and Tic import
machinery. By reconstitution into proteoliposomes the role of
single subunits of the Toc complex as well as the regulation of import
receptors by GTP as driving force across the outer membrane
have been described.
Additionally, electrophysiological methods were used to characterize
the channel properties of both the outer and inner envelope
localized protein import pore. All collected data from the
lab demonstrated that the import machinery of transport is
unique compared to other organelles like mitochondria (Group
Boelter and Schleiff).
The second aspect concerns solute transport across the chloroplast
outer envelope. Like the prokaryotic ancestors chloroplasts
have retained multiple ion channels, which act as a selective
molecular sieve for metabolite transport in and out of the organelle.
Outer envelope solute channels clearly regulate metabolic
networks in the plant cell and fulfill essential functions in
chloroplast differentiation (Group
Philippar).
A third project of the group deals with the processes involved in the
biogenesis and differentiation of chloroplasts and their
prokaryotic progenitor cyanobacteria. In particular the distribution
of protein translocons in chloroplasts and cyanobacteria as
well as their contribution to the formation of thylakoids,
inner envelope and plasma membranes are studied (Group
Huenken).
Focus of the fourth project is the biochemical and molecular
characterization of components involved in thylakoid
biogenesis and how this process is regulated in correlation with the
metabolic needs of the surrounding cell (Group
Vothknecht).
Methods used in the lab include (among others) the use of GFP fusions
together with confocal laser scanning microscopy to localize
proteins within the chloroplast. BN-PAGE as well as
lipid chromatography and negative-stain EM are also employed
to study complex formation between
proteins.
Model organisms used in the group are:
- higher plants like Arabidopsis thaliana, Nicotiana
tabacum and Pisum sativum,
- the moss Physcomitrella patens,
- the green algae Chlamydomonas
reinhardtii and
- Cyanobacteria like Synechocystis and
Anabaena
|
|
|
Ludwig
Maximilians-Universität München, Fakultät
für Chemie
|
| |
 |
Prof. Dr. Patrick Cramer
Institut für Biochemie und Genzentrum
der Universität München,
Feodor-Lynen-Str. 25,
81377 München,
Germany
Tel.: 089-2180-76953,
Fax: 089-2180-76999
This e-mail address is being protected from spambots. You need JavaScript enabled to view it
http://www.lmb.uni-muenchen.de/cramer/index.html
|
|
Research Interests:
Gene expression in eukaryotes is mainly regulated at the level of mRNA
transcription by RNA polymerase II. Over the last years we
could elucidate many aspects of the transcription mechanism
by determining three-dimensional structures of RNA polymerase II alone
and in various functional complexes that reflect snapshots of
the transcription cycle. Our work demonstrated the feasibility
of X-ray crystallographic analysis of large and transient
multiprotein complexes, and is a great starting point for
further mechanistic analysis of gene transcription. Over the next
years, we want to work towards the structures of even larger
and more transient multicomponent transcription complexes. We
want to elucidate protein-protein, protein-peptide, and protein-nucleic
acid interactions that underlie gene transcription and its
regulation. Our main experimental tool will remain X-ray
crystallography, supported by a variety of biochemical and molecular
biology techniques in a modern interdisciplinary research
setup. Our long-term goal is a mechanistic understanding of
gene regulation by structure-function analysis of RNA polymerase II. We
wish to obtain a detailed three-dimensional movie of the mRNA
transcription machinery passing through the transcription
cycle.
|
| |
|
Max-Planck-Institut für
Biochemie/Martinsried
|
| |
|
Prof. Dr. Wolfgang
Baumeister
MPI für Biochemie,
Abt. Mol. Strukturbiologie
Am Klopferspitz,
82152 Martinsried,
Germany
Tel.: 089-8578-2652/2642
(Sekr.),
Fax: 089-8578-2641
This e-mail address is being protected from spambots. You need JavaScript enabled to view it
http://www.biochem.mpg.de/baumeister/
|
|
Research Interests:
With the advent of computer-controlled electron microscopes and the
automation of data acquisition it became possible to obtain
molecular-resolution (2-4 nm) tomograms of structures as
large as organelles or whole cells. Non-invasive three-dimensional
(3-D) imaging of vitrified cells is where cryoelectron
tomography promises to make unique contributions by closing the gap
between the cellular and the molecular world. The emerging
picture of the cell is one of a giant and highly dynamic
supramolecular assembly – hitherto a largely uncharted
territory. Tomograms of cells at molecular resolution are
essentially 3-D images of the cell’s entire proteome and they
reveal the spatial relationships of macromolecules in the
cytoplasm, the ‘interactome’. In order to exploit
the imposing amount of information contained in a cellular
tomogram sophisticated pattern recognition techniques must be
used capable of detecting and identifying molecules in tomograms with a
low signal-to-noise ratio through their structural signature.
The ultimate goal is to obtain through a combined proteomics
– electron tomography approach a comprehensive 3-D molecular
atlas of cells and organelles and to reveal the principles of
supramolecular organization which provides the basis for
higher cellular functions.
|
| |
|
|
|
Prof. Dr. Franz-Ulrich
Hartl
Am Klopferspitz 18a,
82152 Martinsried,
Germany
Tel.: 089-8578 2233
Fax: 089-8578 2211
This e-mail address is being protected from spambots. You need JavaScript enabled to view it
http://www.biochem.mpg.de/hartl/
|
|
Research Interests:
The Department of Cellular Biochemistry, Max Planck Institute of
Biochemistry, is investigating the mechanisms of protein folding in the
cell. Protein folding is required for the realization of genetic
information at the level of functional proteins and as such is one of
the most fundamental reactions in all of biology. The long-term goal is
to reach a complete understanding, at the structural and functional
level, of how the machinery of molecular chaperones assists in co- and
posttranslational protein folding. Of special interest are the folding
pathways in the cytosol of prokaryotes and eukaryotes. Using a range of
methods from biophysical to cell biology, the Department ultimately
seeks to decipher the rules by which the thousands of different
proteins in the cytosol utilize the chaperone machinery for de novo
folding and assembly. A second focus of research concerns the molecular
mechanisms underlying neurodegenerative disorders, such as prion
diseases and polyglutamine diseases, which are caused by aberrant
protein folding and are associated with the formation of protein
aggregates. Here the wish is to understand how protein misfolding
causes cytotoxicity and how molecular chaperones act as protective
modulators. It is planned to harness the power of the chaperone
machinery for applications in biotechnological protein production and
in combating disease.
|
|
|
Technische Universität
München, Fakultät für Chemie
|
|
|
Prof. Dr. Johannes Buchner
Institut für Organische Chemie und Biochemie, Lehrstuhl
für Biotechnologie der TU München
Lichtenbergstr. 4,
85747 Garching,
Germany
Tel.: 089-289-133-41
Sekr.: 089-289-133-40
Fax: 089-289-133-45
This e-mail address is being protected from spambots. You need JavaScript enabled to view it
http://www.chemie.tu-muenchen.de/biotech
|
|
Research Interests:
Proteins adopt their three-dimensional structure in a spontaneous
reaction, determined by the noncovalent interactions of amino acid side
chains. In the case of cysteine residues, covalent linkages
may contribute to the stability of the three dimensional
structure. In vivo, a set of helper proteins, called
molecular chaperones, exists which assists protein folding.
Many members of this functionally related group belong to the so-called
heat shock proteins. In addition, folding catalysts for slow
reactions, such as disulfide bond formation, exist. One of the
key functions of these folding helper proteins is to prevent
unproductive side reactions such as the unspecific
interaction of (un)folding polypeptide chains which lead to the
formation of aggregates, e.g. inclusion bodies upon
overexpression of recombinant proteins in biotechnological
processes. Our research interests can be divided in two major
areas: 1. Understanding the principles and limitations of the
folding of multidomain proteins. One of the model proteins studied are
antibodies. The structure formation process of these proteins
includes folding, formation of disulfide bonds, prolyl
isomerization, and domain association. 2. Analysis of the molecular
mechanisms of chaperone proteins. We study the major classes
of molecular chaperones with a focuson the Hsp90 family and
small heat shock proteins. This involves the analysis of the structure
function relationship and the dynamics of conformational
changes upon ATP hydrolysis.
|
|
|
|
|
Prof. Dr. Michael Sattler
Department Chemie der TU
München und Helmholtz Zentrum München
Lehrstuhl für Biomolekulare NMR-Spektroskopie
Institute of Structural Biology
Lichtenbergstr. 4,
85747 Garching,
Germany
Tel.: 089-289-133-41
Sekr.: 089-289-133-40
Fax: 089-289-133-45
This e-mail address is being protected from spambots. You need JavaScript enabled to view it
http://www.nmr.ch.tum.de/
|
|
Research Interests:
A main focus in
the Sattler group is to understand the structural basis of protein-RNA
interactions that are functionally important for various aspects of
gene expression, including the regulation of (alternative) pre-mRNA
splicing and gene silencing by non-coding RNAs (siRNAs, miRNAs). About
75% of all human genes are alternatively spliced and misregulation of
splicing is linked to various human diseases. The spliceosome is a
highly dynamic machinery, which involves numerous protein-RNA
interactions. During the different steps that eventually lead to
splicing of the pre-mRNA, these complexes are continuously rearranged,
and their composition can be modulated, for example in the context of
alternative splicing. While this requires that the molecular
interactions are dynamic, specific and tight complexes are formed by
the cooperative combination of multiple weak protein-protein and
protein-RNA interactions. NMR is well suited to study such dynamic and
transient interactions in solution. Current projects focus on
protein-protein and protein-RNA interactions that play important roles
in splicing and other aspects of RNA metabolism.
Another area of research is structural investigations of proteins and
protein complexes involved in signaling. Here, we focus on proteins in
signaling pathways that are linked to human disease.
We are also initiating studies for the structure-based design of small
molecular inhibitors as i) starting points for pharmaceutical
interference and ii) as tools to modulate and monitor cellular
signaling. These studies aim at identifying optimized small chemical
compounds using structure-guided approaches. NMR is an efficient tool
for such a structure-based chemical biology approach since it not only
allows to determine the three-dimensional structures in solution but
also is efficient in detecting and mapping ligand binding of
biomolecules.
|
|
Alumni groups
|
|
The following
groups have participated in the doctorate program in the past:
|
|
|
Prof. Dr. Ralf-Peter Jansen
former adress:
Genzentrum und Institut für Biochemie
der Universität München
current
address:
Interfakultäres Institut für Biochemie
der Universität Tübingen
Hoppe-Seyler-Str. 4,
72076 Tübingen,
Germany
Tel.: 07071-29-72453
This e-mail address is being protected from spambots. You need JavaScript enabled to view it
http://www.ifib.uni-tuebingen.de/
|
|
Research Interests:
Protein synthesis in the cytoplasm can be temporally and spatially
controlled by mRNA localization and translational regulation.
RNA
localization has been described in a variety of organisms
ranging from
fungi to plants, invertebrates, and vertebrates. We would like to
understand how localized RNAs are exported from the nucleus,
how they
are transported through the cytoplasm, and how they are
anchored at
their target position. In order to
understand these mechanisms, we
are using budding yeast as a model system. In yeast, several
mRNAs are
localized to the bud cortex during mitotic growth, including some
that
control cell fate, cell cycle and signalling. The major factors of the
machinery that targets them to the bud have been genetically
identified and characterized. They include a myosin motor protein,
a
myosin-specific chaperone, several RNA-binding proteins and additional
associated proteins. To date it is
unknown how all these components
act in concert and how the translation of mRNAs is repressed
during
trafficking. In addition, it is not understood where ribonucleoprotein
complexes that move a localized RNA assemble and how they
disassemble
at the target site. Using a combination of
immuno-fluorescence, FISH,
life imaging and biochemical methods we want to understand
the
molecular mechanism of cytoplasmic RNA trafficking and how it is linked
to other aspects of RNA metabolism like processing,
translation and
RNA decay.
|
|
Institutes
