Target Discovery in Disease and Drug Development

Currently, target discovery efforts typically follow one of two strategies that differ in the way they lead to target identification and small compound selection and optimization. For both target-based and phenotype-based workflows, proteomics enables a multitude of investigations relevant to the different steps and addressing different questions in the process (Figure 1).

A state-of-the-art mass spectrometry platform is established in the TDI with the aim to develop and expand existing efforts in the Kessler group and the Central Proteomics Facility in close collaboration with the laboratories of Prof. Stephan Knapp (SGC), Prof. Christopher Schofield (CRL) and the cell screening facility (Dr. Daniel Ebner, TDI). These will include the following strategies:

A. Discovery and characterisation of key molecules and pathways in disease

• Special focus on the Ubiquitin system and MHC antigen presentation
• HIV vaccine development
• Autoimmune diseases

B. Characterisation of drug-protein interactions

• Drug/compound led chemoproteomic profiling
• Target deconvolution and selectivity profiling
• Binding mode-centric profiling
• Activity-based profiling

C. Drug/compound mode of action and target discovery/validation

• Protein-protein interactions
• Global proteome and PTM profiling

D. Biomarker discovery and preclinical drug discovery

• Proteomic biomarkers for evaluating drug efficacy/toxicity
• Prognostic and predictive biomarkers in disease
• Cancer and hypoxia
• Renal diseases (stone)