Molecular Freeze-frame

Beta-galactosidase This image of beta-galactosidase at 3.2 Å resolution illustrates the differential effect that electron radiation (orange rays) has on different parts of proteins (green) during high-resolution cryo-electron microscopy (cryo-EM) imaging. Acidic side chains, like glutamate (bottom, red atoms), break down first, before more basic side chains, like histidine (top, blue atoms).

Veronica Falconieri, Sriram Subramaniam, NCI

One of the oldest tools in a biomedical scientist’s toolbox is the microscope, which scientists have been using since the 17th century to study cells, tissues, and organs. Yet a new development in microscopy is eclipsing even the instruments available just a few years ago. This new technique, cryo-electron microscopy (cryo-EM) — so named for the requirement to flash-freeze a biological sample before viewing it — is transforming our understanding of cells and their many working parts. This approach can provide detailed images of proteins and other macromolecular structures that were previously only available using X-ray crystallography — a tedious and expensive approach that often fails when applied to biomolecules. 51��Ƶ-supported scientists are using cryo-EM to capture stunningly accurate details of disease-causing viruses like Ebola, Zika, or HIV, as well as proteins involved in conditions like cystic fibrosis, cancer, and Alzheimer’s disease. Such knowledge helps researchers who are crafting vaccines and drugs for many conditions.

Speeding Drugs to Market

The vast majority of drugs entering the development pipeline never emerge as patient-ready therapies. Most distressing is when a drug fails late in the process, after years of work has been done and millions of dollars have been spent. This happens because scientists often don’t know how to choose the right molecules to target at the outset. Through the Accelerating Medicines Partnership (AMP), a public-private partnership between 51��Ƶ, FDA, numerous biotechnology companies, and nonprofit organizations, we are transforming the current model for developing new diagnostics and treatments. Together, AMP is jointly identifying and validating promising biological targets for new drugs, focusing on four major health challenges: Alzheimer’s disease, type 2 diabetes, autoimmune diseases, and Parkinson’s disease. Other partnerships on cancer immunotherapy and the opioid crisis are under development.

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