Analytical Ultracentrifuge

• Subject Area: Basic Research in Biology and Medicine
• Term: Funded in 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 540188626

The device applied for is an ultracentrifuge equipped with various detection optics for analytical purposes. This newly developed device differs from the predecessor models in particular in that it has interference optics and absorption optics with a multi-wavelength function, which create the prerequisites for new applications in the analysis of biological macromolecules and macromolecular complexes. The Institute's great interest in the mechanisms of protein aggregation gives rise to numerous questions that can be addressed in particular by using the modern technique of analytical ultracentrifugation (AUZ). With this method, sedimentation coefficients (s-values) and s-value distributions, diffusion and friction coefficients, equilibrium and rate constants, suspended densities, shape parameters and molecular masses can be determined. These parameters provide versatile structural information, which can be obtained without the use of a label and in a wide range of possible solvents, i.e. in solution. In addition, analytical ultracentrifugation as an absolute method represents a crucial possibility for validating or complementing other, partly surface-based, biophysical techniques. The project consists in the characterisation of self- and heteroassociation of proteins, whose misfolding and the resulting aggregation are assumed to be the cause of numerous human diseases. Mechanistic investigations of amyloid formation with a focus on oligomers are the basis for further work that involves either cellular components, such as lipid membranes, or self-developed drug candidates as interaction partners. In particular, the analysis of mixtures of different macromolecular components only becomes feasible with the availability of multiwavelength detection in combination with interference optics, as this allows the concentration gradients created under the influence of the centrifugal field to be broken down into the contributions of individual components. With the availability of the large-scale device described above, essential, open questions of amyloid protein aggregation can be addressed.

• DFG Programme: Major Research Instrumentation
• Major Instrumentation: Analytische Ultrazentrifuge
• Instrumentation Group: 1210 Ultrazentrifugen (über 25.000 1/Min)
• Applicant Institution: Heinrich-Heine-Universität Düsseldorf
• Leader: Professor Dieter Willbold, Ph.D.