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March
2010
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Aims
The aims of the project are:
- Identification of
cancer-related mutations by database mining, high-throughput sequencing
of cancer tissues and established cancer cell lines (focus: cancer of
prostate, stomach, colon, breast).
- Characterisation
of these mutations on a functional level and molecular pathway level in
cells and mouse model. This analysis will focus on the common traits of
cancer: enhanced cell mobility, unrestricted cell growth, tissue
invasion, reduced cell mortality, altered response to extra-cellular
stimuli.
- Determination of cellular parameters: protein
level, protein modifications and mRNA expression in response to wild
type and mutant protein expression in defined isogenic cell lines.
- Comparison of these data with patient data, tissue parameter (protein
& mRNA expression, mutations) and clinical parameters (metabolism,
disease progression).
- Modelling of quantitative
parameters obtained from our experimental and clinical data for
their effect on the main cellular signalling pathways.
- Development of predictive models for the clinical use of
chemotherapeutics, environmental determinants on diseases as well as
for predicting disease progression in general.
- Translation of our modelling approach and our experimental results to
the clinical sector/Public Health for improved prevention, diagnosis
treatment and new drug target identification.
- Identification of new molecular targets for the development of site-specific chemotherapies.
- Establishment of a bed-side mutational profiling tool based on the
Solexa sequencing technique and transfer to routine diagnostics.
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