Project description DEENESFRITPL A novel thrombosis test Antithrombin (AT) is a liver-secreted protein that regulates the coagulation system by inactivating specific enzymes in the pathway of blood clotting. Diagnostic tests of AT deficiency rely on its activity, disregarding the existence of many different proteoforms and their clinical meaning. The EU-funded HarmonizATforms project is working to harmonise AT tests and develop an assay that generates clinically meaningful results. Researchers are investigating all clinically relevant ATs and will develop a test based on mass spectrometry rather than on immunoassay, which is the current gold standard. The test is expected to bring diagnostic superiority in the fields of thrombosis and haemostasis. Show the project objective Hide the project objective Objective Current medical tests for antithrombin deficiency generally measure the overall activity, being blind for the actual proteoforms of AT that contribute to the test. To ensure accurate test results, a traceability chain needs to be in place, which requires the accurate definition of the exact analyte to be measured. I hypothesize that an in-depth understanding of the pathological molecular proteoforms of antithrombin (AT) will allow for the identification of clinically relevant proteoforms and enable test harmonization, resulting in a test with a well-defined clinical outcome that are actionable by clinicians. Mass spectrometry (MS) is an emerging technique in the field of clinical chemistry, which is well suited for the detection of proteoform characteristics and outperforms testing methods based on immunoassays. Therefore my aims are 1. To develop a mass spectrometry based test for the quantification of individual characteristics of molecular proteoforms of AT. 2. Analytically validate the developed method according to clinical chemistry procedures, and 3. Assess the role of MS based test for the standardization of AT tests. I am a passionate scientist with a strong background in the development of MS-based tests for proteins. I plan to perform the project in collaboration with my supervisor, who has large experience in medical test development and the ECAT foundation, who is specialized in proficiency testing of AT and test harmonization. This project will allow me to obtain skills and experience to oversee and develop a clinical test from biomarker discover to test evaluation and implementation, specifically in the niche of thrombosis and haemostasis, as well as the transferable skills required to eventually establish my own independent research group. Fields of science medical and health sciencesclinical medicineangiologyvascular diseasesnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural scienceschemical sciencesanalytical chemistrymass spectrometry 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-2018 - Individual Fellowships Call for proposal H2020-MSCA-IF-2018 See other projects for this call Funding Scheme MSCA-IF-EF-RI - RI – Reintegration panel Coordinator ACADEMISCH ZIEKENHUIS LEIDEN Net EU contribution € 187 572,48 Address ALBINUSDREEF 2 2333 ZA Leiden Netherlands See on map Region West-Nederland Zuid-Holland Agglomeratie Leiden en Bollenstreek 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 € 187 572,48
