Functional Genome Analysis  (B070)
Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 580
D-69120 Heidelberg, Germany.
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   Functional Tumour Analysis     /     Proteomics     /     DNA Technologies     /     Epigenetics     /     RNA Diagnostics 
  Overview


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Summary of Scientific Activities
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   Functional Tumour Analyses
   Proteomics    Synthetic Biology
   How to find us
       - Pancreatic Cancer
       - Antibody Microarrays        - ERASynBio
   Open Positions
       - Other Tumour Entities        - Protein Microarrays        - In Vitro Protein Syntheses
   Group Members
       - Global Knockdown/Knockout Analyses
       - Cancer Studies    
       - A Typical Day …

       - Personalised Proteomics    DNA Methylation

   Transcript Studies        - Subgroup Affinity Proteomics        - Highly Informative Common Cancer Marker 
   Publications / Patents
       - MicroRNA Diagnostics in Blood  
       - Correction of Measurement Biases

       - MicroRNA Based Regulation    DNA / RNA Technologies

   Archive
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Research at the division aims at the development and immediate application of technologies for an assessment and description of the realisation and regulation of cellular function from genetic information. On this basis, we are establishing systems for (early) diagnosis, prognosis and an evaluation of the success of disease treatment. Analyses on tumour material are at the centre of attention, with a particular emphasis on pancreatic cancer. Studies are under way on elucidating the effects on cellular functions of DNA sequence and methylation variations; transcript level profiles were determined of both mRNA and microRNA; concomitantly, the actual protein expression is analysed
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Concerning technical developments, a particular focus is currentlyon the analysis of protein variations and interactions. Proteins are involved in basically all vital processes and most current therapeutic agents target proteins. We have established the means for analysing proteomic variations by affinity-based processes, particularly although not exclusively, on antibody-, protein- and peptide-microarrays. Assays have been established, which exhibit a robustness and reproducibility that meet the requirements of clinical applications. For improved sensitivity and absolute quantification, we developed methods for single molecule detection. Also, various auxiliary facets such as appropriate protocols for protein extraction from various sample types have been established.
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Taking advantage of the above processes, we pursue the identification of disease-relevant protein isoforms. Structural variation is often an immediate indicator for a different functional activity and could also allow a specific intervention. In addition, measurements of protein interactions are performed at a large scale. Processes are being utilised toward the identification of variations that occur in tumours of individual patients at a personal level. Another focus is the creation of a map of communication between the different cell types of the tumour microenvironment.
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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.
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Another line of work aims at a combination of technical advances and access to global biological information toward an in vitro implementation of complex biochemical processes. Motivation is their utilisation in synthetic biology activities for the production of molecules and the establishment of artificial molecular systems. Cell-free biosynthetic production will become important for many biotechnological, immunological and pharmacochemical challenges. Artificial experimental systems, on the other hand, are meant to complement current Systems Biology. By means of such in vitro systems, biological models can be evaluated experimentally. Recently, we succeeded in establishing an international consortium to such ends. Similar to physics, insight into cellular functioning will be gained by an iterative processing of information by experimental and theoretical systems biology. Eventually, this may lead to the establishment of a fully synthetic self-replicating system and - in the long run - an archetypical model of a cell.
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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 were spun-off, which pursue some of the results at a commercial level.








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