WEBINAR
Frank Bernhard’s Cell-Free Workflow for Cryo-EM–Ready Membrane Protein Complexes
Unlock GPCRs and other challenging membrane proteins with a cell-free expression workflow that delivers cryo-EM–ready complexes and connects in vitro structures to in vivo function.
Sign up:
Summary
Membrane proteins sit at the heart of signalling and transport, and many of the most valuable drug targets. But they’re also some of the hardest proteins to express, stabilise, and push all the way through to high-resolution structure and functional validation.
Join Dr Frank Bernhard (Goethe University Frankfurt), a world-leading expert in cell-free membrane protein expression, to explore a practical cell-free membrane protein expression workflow based on tuned E. coli lysates and tailored nanoparticle/lipid environments. You’ll see how nascent membrane proteins are inserted co-translationally into nanodiscs, how nanoparticle-based size exclusion (NSEC) is used as a rapid, general quality-control tool, and how this enables cryo-EM–grade GPCR/G protein complexes to be produced as full-length receptors, no truncations or fusion partners.
Dr Bernhard will also introduce a nanotransfer technique that moves cell-free synthesized GPCRs into living cell membranes, bridging in vitro structural insights with in vivo functional readouts. Whether you’re working on GPCR structural biology, transporters, channels, or other difficult membrane targets, this session will give you concrete strategies to shorten timelines from construct to structure and function.
In this webinar, you’ll learn how to:
- Use cell-free membrane protein expression in tuned E. coli lysates to bypass cell culture bottlenecks and detergent extraction while retaining native-like folding.
- Generate cryo-EM–ready GPCR/G protein complexes and other membrane proteins as full-length constructs, revealing ligand binding and regulatory loop mechanisms that are often hidden in engineered constructs.
- Apply a nanotransfer approach to reinsert cell-free synthesized GPCRs into mammalian cell membranes, enabling functional and interaction studies that connect structure to signalling.
By the end of the session, you’ll:
- Be able to outline a complete cell-free workflow for membrane protein production, from DNA template design and lysate choice to nanoparticle integration and structural analysis.
- Know which parameters to tune (lysate composition, nanoparticle systems, ligands, NSEC readouts) to get better yields and higher-quality membrane protein complexes.
- Understand how cell-free protein synthesis can de-risk membrane protein projects, from early discovery and target validation through to structural biology and mechanistic studies.
- Have new ideas for bridging in vitro and in vivo experiments using nanotransfer-based insertion of receptors into live cell membranes.
This webinar is designed for:
- Structural biologists and cryo-EM scientists working on GPCRs, transporters, channels, and other membrane proteins
- Membrane protein and GPCR researchers in academia and industry
- Biophysicists and protein chemists exploring alternatives to traditional cell-based expression
- Drug discovery and pharmacology teams looking to unlock new membrane targets and improve success rates
- Protein expression and purification specialists evaluating cell-free protein synthesis platforms
Speaker:
Recent peer-review publications:
- Cryo-EM structure of cell-free synthesized human histamine 2 receptor/Gs complex in nanodisc environment. Nat. Commun. 15, 1831 (2024).
- Transfer mechanism of cell-free synthesized membrane proteins into mammalian cells. Front. Bioeng. Biotechnol. 10, 906295 (2022).
- Cryo-EM structure of a cell-free synthesized full-length human β1-adrenergic receptor in complex with Gs. Structure 33, 1867–1877.e5 (2025).
About eProtein Discovery
Nuclera's eProtein Discovery™ system combines digital microfluidic droplet automation with cell-free protein synthesis technologies, it empowers protein scientists to identify the best conditions for expressing and purifying proteins of interest within 24 hours, all on a single consumable cartridge.
The system offers a significant advantage over traditional protein expression methods, allowing researchers to save time and resources by simplifying and automating the process. Its ability to handle multiple genes and customizable cell-free blends makes it a valuable tool for protein scientists in academia and the biopharma industry.
