Descripción del proyecto
Una nueva prueba para la trombosis
La antitrombina (AT) es una proteína secretada por el hígado que regula el sistema de coagulación inactivando enzimas específicas en la ruta de coagulación de la sangre. Las pruebas de diagnóstico de la deficiencia de AT se basan en su actividad y no tienen en cuenta la existencia de numerosas proteoformas diferentes ni su significado clínico. El proyecto financiado con fondos europeos HarmonizATforms se propone armonizar las pruebas de AT y desarrollar un ensayo que obtenga resultados con relevancia clínica. Los investigadores están estudiando todas las AT relevantes clínicamente y crearán una prueba basada en la espectrometría de masas, en lugar del inmunoensayo empleado ahora como método de referencia. Se prevé que la prueba mejore considerablemente el diagnóstico de la trombosis y la hemostasia.
Objetivo
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.
Ámbito científico
Programa(s)
Régimen de financiación
MSCA-IF-EF-RI - RI – Reintegration panelCoordinador
2333 ZA Leiden
Países Bajos