Pressure-Jump NMR · Investigation of aggregation-prone and phase-separating systems using Pressure-Jump NMR

Investigation of aggregation-prone and phase-separating systems using Pressure-Jump NMR

Proteins are the molecular machines that sustain life. They fold into precise shapes to perform their biological functions, but when this process goes wrong, proteins can clump together and form aggregates. Such aggregation underlies many serious diseases, including Alzheimer’s, Parkinson’s, and type II diabetes. Despite decades of research, we still struggle to observe and understand how proteins aggregate and separate into different liquid phases inside cells, because these processes are extremely fast and difficult to capture experimentally. The Pressure-Jump NMR (PJ-NMR) project set out to establish a completely new way of studying these dynamic protein behaviors. Using controlled bursts of pressure, PJ-NMR allows us to trigger and observe molecular changes as they happen, at the level of individual atoms. This new experimental approach promises to reveal details of how proteins interact, fold, and form aggregates or droplets — processes central to many biological functions and disease mechanisms. The project’s main objectives were to: -Design, build, and validate a new PJ-NMR instrument in Europe. -Develop new measurement methods to capture the rapid molecular events following a pressure change. -Apply these methods to study proteins involved in aggregation and liquid–liquid phase separation. -Lay the foundation for a sustainable European research platform capable of using PJ-NMR to tackle urgent biomedical challenges. By advancing both instrumentation and methodology, the project addresses a major scientific need: to connect the static structural information available from conventional techniques with the dynamic, real-time processes that drive disease and biological function. In the long term, this technology will contribute to Europe’s capacity to study, diagnose, and eventually control protein misfolding diseases — an area of increasing health and economic significance given the ageing population.

Data: CORDIS, © European Union