Unit 4

 
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Unit 4: Cellular Models

NanoCAN's UNIT 4 uses a newly developed technique for the easy construction of isogenic cancer cell lines via a site-specific recombination technique. Isogenic means that the resulting panels of cells are genetically identical except for the gene or miRNA under investigation or except for the inserted reporter or silencing construct. Besides acting as the center's core facility for the construction of stable cell lines, UNIT 4 comprises the following major subprojects to develop new tools and methodology, which incorporates staff members, working interdisciplinary also in the other units of the center: 

The main goal of this subproject is to systematically explore genes and miRNAs known or suspected to be related to the CSC-phenotype for their ability to "arrest" cancer cells in the CSC-state and to consecutively characterize these cells. Furthermore, a broader panel of cell lines is generated, in which the CSCs are marked with different reporter constructs in order to trace their individual fates in a complex population.

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The goal of this project is to develop the tools and conditions for detecting CSC-markers in protein preparations of cells, which are arrayed on a chip format. The challenge associated with this is to find the appropriate balance between the accurate quantification of the CSC-markers in minute amounts of protein (corresponding the protein content of a single cell or less) and to achieve a sufficiently high throughput, so that the method can be used for future diagnostic approaches as well as for systematic large scale screens (see also: Unit 5).

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This subproject explores a particular drug target, for which previous data indicated that is causes synthetic lethality to cancer cells. The main goal is to determine, whether addressing this drug target also causes synthetic lethality at the level of the CSCs in order to test the underlying concepts. Besides that, we use this system to derive general rules for the design of synthetic lethal nucleic acid-based drugs regarding selectivity, reduction of unspecific toxicity, stability and efficacy.

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