 Research
at the division focuses on the
development and application of
technologies
for an assessment and description of the realisation and regulation of
cellular
function from genetic information. Analysis of
tumour material is
at the centre of attention, with an emphasis on pancreatic
cancer and
personalized approaches. The effects of DNA sequence variations and the
epigenetic
modulation of the genome are studied. This is combined with
measurements on variations in transcription factor binding and changes
in transcript
levels of coding and noncoding RNAs. Concomitantly, the actual protein
expression is
analysed. We
complement molecular analyses with functional studies for the
elucidation of
relevant cellular mechanisms.
..
Beside the creation of basic scientific
knowledge, we aim at establishing means for early and non-invasive
molecular
diagnosis as a basis for accurate prognosis, reliable patient
stratification,
and a precise monitoring of treatment results. Another objective is the
identification of new therapeutic approaches.
..
Technically,
we pursue
particularly developments in the field of proteome
analysis. We have established affinity-based processes that
permit a robustness
and reproducibility that meet the requirements of clinical applications
and are
amendable to translation. Also, various auxiliary facets such as appropriate
protocols
for protein extraction from various sample types have been established.
One scientific aim is the identification of
disease-specific protein isoforms. Structural variation is often an
indicator
for different functional activity. Also, measurements of protein
interactions
are performed, in particular for the identification of variations that
occur at
a personal level. A third activity is the creation of a map of the
protein-mediated communication between the different cell types of the
pancreatic
tumour microenvironment.
..
All the above forms the basis for functional
analyses toward the
definition of cellular mechanisms and the identification and evaluation
of potential therapeutic avenues. Both targeted experiments are performed, such as detailing the effect of methylation variations
in gene promoters on particular pathways, as well as global
studies, for example genome-wide shRNA knock-down or CRISPR-Cas
mediated knockout studies and related over-expression
analyses.
Functional consequences of observed molecular events are
studied in detail in cell lines, xenograft mice and mouse models, or directly on
patient samples.
..
Another line of work aims at
the fully synthetic, in
vitro implementation of complex biological processes.
Motivation is their utilization in synthetic
biology activities for the
production of biomedically active
molecules, such as non-immunogenic agents, and the establishment of an
entirely
artificial molecular system. Cell-free biosynthetic production will be
crucial
for mastering many biotechnological and pharmacochemical challenges.
Artificial
biological systems will complement Systems Biology by evaluating
biological
models experimentally. Similar to physics, insight into cellular
function will
be gained by an iterative process of performing experimental and
theoretical
Systems Biology. Eventually, this may lead to the establishment of a
fully
synthetic self-replicating system and, ultimately, an archetypical
model of a
cell.
..
Many
projects are pursued in
national and international collaborations and programmes. Apart from publications in
scientific journals, the division filed a substantial number of patents / patent
applications, of which several have been licensed out or are being
utilised in
ongoing collaborations with commercial partners. Also, companies have
been spun-off, which pursue some of the results at a commercial level.
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