Why are the most fundamental structural parts of the human body referred to as cells? Robert Hooke, the man who coined the term, thought they looked like cells in a monastery.
But without a picture, this analogy would never have been possible. Microscopes, the fundamental instruments that make these pictures possible have gone a long way from 1665, when Hooke made his discoveries. Hooke looked at dead cells while today, we freeze biochemicals to view metabolic processes as they happen. Cryo-electron microscopy does exactly this and has revolutionized the science of biochemistry.
Scientists Jacques Dubochet, Joachim Frank and Richard Henderson developed Cryo-EM to examine the structure of biomolecules in high-resolution. After decades of development, they received the 2017 Nobel Prize in Chemistry for breakthroughs on the technology that enables three-dimensional imaging of proteins, viruses, bacteria and more.
At Cornell, Prof. Lena Kourkoutis, applied and engineering physics, has collaborated with other researchers across disciplines to use and build upon Cryo-EM.
Breakthroughs in Cryo-EM were first made when Frank developed an image processing method to convert blurry two-dimensional figures into clear three-dimensional ones between 1975 and 1986. Dubochet developed vitrifying water, which allowed biomolecules to retain their natural shape in the harsh vacuum used in electron microscopes. In 1990, Henderson succeeded in creating a clear three-dimensional image of a protein at atomic resolution. All in all, it was a process of constant improvement that lead to the technology that allows scientists to regularly develop three-dimensional images of biomolecules.
Like many other scientific instruments, Cryo-EM has developed in both the life sciences and physical sciences in parallel.
“It’s so important to be open to the ideas of your peers; you can really transform your method with those ideas,” Kourkoutis said. “Then, you can have much more of an impact.”
Her lab conducts research on nanostructured materials and currently uses scanning transmission electron microscopy and spectroscopy to examine biomaterials. In addition to this, Kourkoutis is interested in looking at fluids, particularly in batteries, and larger slices of cells through Cryo-EM. Though the technology was developed to focus on singular molecules, her lab prioritizes the development of methods that allow the tool to be used in several disciplines.
“Cornell has a strong expertise in methods and instrument development,” Kourkoutis said. “We are using the known methods that they use in biology to solve physical science problems.”
With her team, Kourkoutis uses Cryo-EM to research next level energy devices such as fuel cells or photovoltaic interfaces on entire cells and tissues. In fact, the team has applied Cryo-EM techniques to capture the detailed structure of biological processes. This can then be used by biomedical researchers to understand the function of individual macromolecules within larger networks.
Kourkoutis explained that focussing on developing new methods to use the technology will not only improve imaging in chemistry but also lead to developments in the life sciences, such as in drug development, viewing cell structure and understanding biological processes.
“Researchers across campus must collaborate to improve methods and instrumentation across disciplines, which will lead to greater and more novel discoveries in both life and physical sciences to solve the problems in the world,” Kourkoutis said.