Project description DEENESFRITPL 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. Show the project objective Hide the project objective 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. Fields of science medical and health sciencesbasic medicinepharmacology and pharmacydrug discoverynatural sciencesbiological sciencesbiochemistrybiomoleculesnatural scienceschemical sciencesanalytical chemistrymass spectrometrynatural sciencesphysical sciencesopticslaser physics Programme(s) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Topic(s) MSCA-IF-2019 - Individual Fellowships Call for proposal H2020-MSCA-IF-2019 See other projects for this call Funding Scheme MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF) 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 Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 212 933,76
