European Commission logo
English English
CORDIS - EU research results
CORDIS

MALDI-TOF mass spectrometry metabolite screening assays for drug discovery in human disease

Project description

Advancing drug discovery assays

Discovery of therapeutic targets is a key step in the drug discovery pipeline, where high-throughput screening (HTS) of chemical substances are evaluated in various biological processes. The scope of the EU-funded HTS MALDI-TOF MDD project is to incorporate matrix-assisted laser desorption/ionisation time of flight (MALDI-TOF) mass spectrometry in cellular metabolomics assays. The plan is to investigate how drugs affect different metabolic pathways and simultaneously map the metabolic profile of the cell. Using a pulmonary fibrosis cellular model, researchers will evaluate whether particular metabolites can serve as biomarkers for disease diagnosis as well as a readout in drug discovery assays.

Objective

Discovery for drug targets is a key step within the process of drug development, and is the corner stone in the pharmaceutical industry. This is mostly achieved by high-throughput screening (HTS) approaches in which a large number of chemical substances are assayed for a specific effect or activity in diverse areas of biology. Mass spectrometry (MS) has become a widely adopted tool in this field as it offers the possibility to simultaneously track molecules in a label-free manner, provides excellent signal to noise, reproducibility, assay precision, and a significantly reduced reagent cost when compared to fluorescence-based assays. Matrix-assisted laser/desorption ionisation time of flight (MALDI-TOF) is the most validated surface ionisation method for HTS approaches, but reported applications of this technology have been limited to in vitro assays with simple readouts and to peptide/protein-centric activity assays. To date, comprehensive and unbiased metabolomics based HTS approaches for cellular assays with MALDI-TOF have not been explored. The objective of this fellowship is to set up a MALDI-TOF based cellular assay for HTS metabolomics drug discovery in order to identify a set of metabolites to screen which will enable us to unbiasly and comprehensibly measure, in a HT manner, how drugs affect different metabolic pathways while simultaneously mapping the metabolic profile of the cell. First, I will develop a robust protocol for the detection, identification, and quantification of ~50 small metabolites for cellular assays. Then, I will apply this protocol to track metabolites in a pulmonary fibrosis cellular model, as well as in fibrotic lung tissue sections using MS imaging. The goal is to compare a disease model with the control to see how drugs are affecting these metabolites, and to see if identified biomarkers can be used to identify disease in tissue samples. As a final validation step, I will implement this platform in Boehringer Ingelheim in Germany.

Coordinator

UNIVERSITY OF NEWCASTLE UPON TYNE
Net EU contribution
€ 212 933,76
Address
KINGS GATE
NE1 7RU Newcastle Upon Tyne
United Kingdom

See on map

Region
North East (England) Northumberland and Tyne and Wear Tyneside
Activity type
Higher or Secondary Education Establishments
Links
Total cost
€ 212 933,76