Research
at the division focuses on
the realisation and regulation of cellular function, with an
emphasis on pancreatic
cancer. Pancreatic
ductal adenocarcinoma (PDAC) has currently the worst prognosis of all
solid
tumours and will soon be the second most frequent cause of
cancer-related death
in the Western world. Only very limited therapeutic options and
basically no
means for early diagnosis exist; mortality is close to incidence and
patients
usually survive only few months after diagnosis.
..
We study various
molecular aspects such as the
activating effect on gene expression of hypermethylation in gene promoters by increasing the binding of some transcription factors, and
activities at the level of
coding and non-coding RNAs. Concomitantly, protein functions and
interactions
are investigated, mostly by means of affinity-based assays. All this is complemented with in vitro
and in vivo functional
studies for the elucidation of relevant cellular
mechanisms. Besides creating
basic scientific knowledge, we aim at establishing means for reliable,
potentially early and
non-invasive molecular diagnosis, accurate prognosis, patient
stratification
and treatment monitoring as well as the identification of novel
therapeutic
modalities.
..
Particularly
promising developments are ongoing in the field of proteome
analysis. We have established affinity-based processes of a
robustness
and reproducibility that meet the requirements of clinical applications
and are
amendable to translation. One scientific goal is mapping the
protein-mediated communication between the different cell types of the
pancreatic
tumour microenvironment. We also look for
disease-specific protein isoforms as structural variation is often an
indicator
for functional differences.
..
Other recent work was based on a detailed follow-up of results from genome-wide CRISPR-Cas
mediated gene knockout and related over-expression
experiments with PDAC cells of different matastastic potential.
...
Separate from the
above, we have been working at the in vitro implementation of
fully synthetic, orthogonal biological processes using enantiomeric
biological
molecules (Synthetic Biology). Motivation is their utilisation for the production of
biomedically
active molecules, which are non-degradable enzymatically and
non-immunogenic,
and the establishment of artificial, fully synthetic molecular systems.
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 studies. 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, of which
several have been licensed out or are being
utilised in
ongoing collaborations with commercial partners. Also, several
companies have
been spun-off, which utilise some of the results at a commercial level.
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