Fisher Bioimage Aps

2curex

2curex Aps

Grith Hagel

Ole Thastrup

Morten P Meldal

Bernard Robert Terry

Jens Chr Norrild

Sara Petersen Bjorn

Soren Jensby Nielsen

Morten Hentzer

The present invention relates to a method and tools for extracting information on a compounds influence on a cellular phenotype. The method of the invention may be used as a very efficient procedure for testing the efficacy or resistance of single drugs or combinations of drugs on cells from individual patients. Thus, the methods may be useful for predicting efficacy of a drug on a given patient. The methods are also useful for testing of compounds for toxicity, identifying drug targets for known or novel compounds.

Identifying compounds modifying a cellular phenotype

The present invention relates to methods for identifying compounds capable of modulating a cellular response. The methods involve attaching living cells to solid supports comprising a library of test compounds. The test compounds are linked to the solid support via cleavable linkers and may thus be released from the solid supports. Solid supports comprising cells, wherein the cellular response of interest has been modulated are selected and the test compound of the solid support can then be identified. The cellular response may for example be changes in complex formation between proteins.

Identification of compounds modifying a cellular response

A method is described to assay for protein interactions in living cells, e.g. by the introduction of two heterologous conjugates into the cell. The method uses the measurement of cellular distribution of a detectable component (e.g. a GFP-labeled&#x2dc;fluorescent probe) to indicate the presence or absence of an interaction between that component and a second component of interest. The method uses the knowledge that certain components can be stimulated to redistribute within the cell to defined locations. Inducible redistribution systems make it possible to determine if specific interactions occur between components. Inducible systems are described where it is demonstrated that the redistribution stimuli are essentially 'null', in that they affect no other system in the cell during the assay period, other than the component whose redistribution can be induced. Also described is an extraction buffer which is useful in high throughput screening for drugs which affect the intracellular distribution of intracellular components. The extraction buffer comprises a cellular fixation agent and cellular permeabilisation agent. Optimizing the composition of the extraction buffer and its application to various cell types is described.

Method for extracting quantitative information relating to interactions between cellular components

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Dragor, Denmark

Grith Hagel