Descripción del proyecto
Método microfluídico de cristalización de proteínas de membrana
Determinar la estructura tridimensional de las proteínas de membrana con muestras de cristal explotables representa un importante reto técnico, dada la complejidad e inestabilidad de estas macromoléculas biológicas. A pesar de su importancia como dianas farmacológicas, hasta la fecha solo se han determinado seiscientas estructuras cristalinas únicas de proteínas de membrana. Por consiguiente, existe una necesidad inminente de desarrollar métodos fiables para cristalizar las proteínas de membrana. El equipo del proyecto RAMP, financiado por las acciones Marie Skłodowska-Curie, propone incorporar una tecnología microfluídica al proceso de cristalización para controlar con precisión las condiciones experimentales y las propiedades de los cristales generados. Al centrarse en los transportadores de membrana, los investigadores esperan aportar conocimientos sin precedentes sobre la función de las proteínas diana y allanar el camino para el diseño de fármacos relativos.
Objetivo
Membrane proteins form more than 85% of drug targets, but just 600 unique membrane protein crystal structures have been determined. A better understanding of how to crystallize membrane proteins reliably is therefore urgently required. The Innovative Training Network “RAtionalising Membrane Protein crystallisation” – RAMP will bring together cutting-edge physical chemistry methods for crystallisation condition control and phase diagram exploration, and the development of new lipids and screens in conjunction with industry with the most challenging biological problems. The network includes expert academic and industrial research groups in crystallisation theory, methods development, membrane protein crystallography, drug development and novel structural techniques like time-resolved and neutron crystallography. We will develop new, rational methods for crystallising membrane proteins, focusing particularly on transporters that are also interesting drug targets. The new robust crystallisation methods will also allow us to use emerging European research infrastructures like XFEL or ESS to gain insight into membrane protein function because the techniques will provide the necessary precise control of crystal size.
A structured training programme organized by academia and industry together will equip the early stage researchers with the skills needed for a successful research career in the field of structural biology. Frequent secondments, research visits and meetings between early-career scientists ensure an efficient exchange of ideas and practical experiences between different groups leading to better integration of European research and innovations in structural biology. Supervision and mentoring by several senior scientists will give the researchers a strong scientific education and make them highly competitive in the work place of tomorrow. The work programme here will improve European competitiveness and advance graduate training.
Ámbito científico
- natural sciencesphysical sciencesclassical mechanicsfluid mechanicsmicrofluidics
- natural sciencesearth and related environmental sciencesgeologymineralogycrystallography
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteins
- natural sciencesbiological sciencesbiochemistrybiomoleculeslipids
- natural sciencesbiological sciencesmolecular biologystructural biology
Programa(s)
Régimen de financiación
MSCA-ITN-ETN - European Training NetworksCoordinador
38058 Grenoble
Francia