200kV Cryogenic Electron Microscope

• Subject Area: Basic Research in Biology and Medicine
• Term: Funded in 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 570491209

Structural biology provides snapshots of biological systems with atomic resolution and has yielded unprecedented insights into protein structure, function, and assembly from small peptides to ribosomes and whole viruses. The field has made innumerable contributions to our understanding of biological processes and the development of new medicines. Proteins and their complexes can produce diverse natural products with exquisite bioactivities that frequently serve as starting points for novel treatment of human disease. Protein crystallography has been the mainstay technique for half a century, but over the past ten years cryogenic electron microscopy (cryo-EM) has established itself as the primary technique for the analysis of large and impossible to crystallize biological samples. It can now even provide highly detailed pictures of large, sub-cellular components in their native environment. Our work will use cryo-EM within two main areas: 1. An improved understanding of enzyme complexes and large, multi-domain enzymes involved in natural product biosynthesis: Here the work focuses on ribosomal natural products, polyketides and non-ribosomal peptide biosynthesis. The main driver of this work is our desire to understand enzyme catalysis with the goal to make the systems accessible for bioengineering applications. 2. Interactions of bioactive compounds with their biological targets, with a particular focus on natural products and their derivatives: Natural products possess exquisite bioactivities but frequently require modification to make them amenable for the intended application. Structural information on how these molecules exert their biological effects will allows us to pursue this work in a rational and efficient way with a variety a collaboration partners. Cryo-tomography enables us to study these interactions in the cellular context and open new areas of research that will initially focus on the interaction of cells with each other or other, engineered materials to e.g. developing new materials for transplants. Due to the nature of our samples and areas of interest we require a cryo-EM with an energy filter and tomography capabilities. Cryo-EM presents a key technology for us and our collaboration partners in Germany and internationally.

• DFG Programme: Major Research Instrumentation
• Major Instrumentation: 200kV Kryoelektronenmikroskop
• Instrumentation Group: 5100 Elektronenmikroskope (Transmission)
• Applicant Institution: Gottfried Wilhelm Leibniz Universität Hannover
• Leader: Professor Dr. Jesko-Alexander Koehnke