RESEARCH
To identify, explore, and validate new targets, the Huber Laboratory integrates a wide range of discovery approaches - including small-molecule and phenotypic screening, biochemical and structural biology, protein-protein interaction and chemical proteomics, medicinal chemistry, and genetic perturbation methods such as RNAi and CRISPR-based editing.
By combining these complementary techniques, we aim to generate high-quality chemical probes that illuminate fundamental biology and provide starting points for drug discovery.
CHEMICAL PROBES
Potent, selective and cell-permeable inhibitors that target key regulators of cellular signalling ("chemical probes") are valued reagents in both fundamental and applied biological research. They are essential tools for target validation and provide starting points for translational research projects.
DRUG TARGET DISCOVERY AND TARGET DECONVOLUTION
Chemical Proteomics & Thermal Stability Profiling
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In order to understand the cellular targets of small molecules and drugs we use compound affinity chromatography coupled to protein mass spectrometry often referred to as "chemical proteomics" or "chemoproteomics". This technology allows us to identify the proteins which bind to compounds in cells or tissue which, for example, can help to uncover the mechanism of action of compounds that have emerged from phenotypic screens or drugs that exhibit so-called "polypharmacology". The power of this approach is that in contrast to classical biochemical in vitro screening assays here the compound is exposed to an entire and competitive cellular proteome (thousands of natural full-length proteins with all posttranslational modifications) which provides a much more physiologically relevant context for evaluating the cellular effects of bioactive compounds.
Thermal Stability Profiling enables the profiling of small molecules and metabolites in intact living cells. Here we take advantage of the ligand-induced thermal stabilisation of proteins to unravel the molecular targets of drugs and other bioactive compounds. Please visit our Resources page to download the TP-MAP for quick and easy analysis of 1D - and 2D-thermal profiling datasets.
