 Research
at the division focuses on an analysis
of the realisation and regulation of
cellular
function from genetic information. The
investigation of
tumour material is
at the centre of attention, with an emphasis on pancreatic
cancer. We
complement the molecular analyses with functional
studies for the
elucidation of
relevant cellular mechanisms and the
identification and evaluation
of potential therapeutic avenues.
..
Beside the creation of scientific
and medical knowledge, we work at the
development and refinement of
appropriate methods and technologies. One aim in
this respect is the establishment of means for
an early and non-invasive
molecular
diagnosis, reliable patient
stratification,
and a precise monitoring of treatment results.
..
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. A scientific goal is a quantitative description of protein
interactions, in particular for the identification of variations
that
occur at
a personal level. Another objective is is the
creation of a map of the
protein-mediated communication between the different cell types of the
pancreatic
tumour microenvironment. A third
activity aims at the
identification of
disease-specific protein isoforms; structural variation is often an
indicator
for functional differences.
..
For a functional understanding, both targeted experiments and global
studies are pursued. An example of the former is a detailed analysis of the
activating effect on expression of methylation in gene promoters; for the latter, genome-wide shRNA knock-down or CRISPR-Cas
mediated knockout studies and related over-expression
analyses are performed.
...
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.
..
Recently, an independent group joint us, which works in Molecular
Epidemiology. Their
research is in the area of cancer genetics with a
particular emphasis on melanoma. Specific projects include a study of
genetic
mutations through exome sequencing of primary tumours to identify
patients at
risk of developing advanced disease. Another investigation analyses
genes
involved in telomere maintenance and telomerase activation pathways
with
reference to TERT promoter mutations. Also the role of telomere length
in
cancer risk and survival is investigated. Additional projects include a
study
of genetic variants in cytokine genes and their role in endothelial
disorders
in patients undergoing allogenic stem cell transfer.
..
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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