As Nano3 Technical Director
"The instrument provides state-of-the-art capabilities for cross-sectioning, preparation of sections for Transmission Electron Microscopy and more," he adds, "but what truly differentiates it is the novel cryo-capability, which will make it possible for cell biologists to see the structures of biological cells in higher resolution to better understand how cells function at a molecular level. This could possibly pave the way for new treatments and drug discovery."
Villa notes that UC San Diego has an established academic tradition in the area of molecular imaging - most notably reflected in the work of biochemist
"What I'm doing is similar," explains Villa, "only I'm using electron microscopy, which gives us higher-resolution images. The idea behind our method is to bring together people who do structural biology with people who do cell biology by using a new tool that will allow us to see the structures of the cells, at high resolution, and better understand what molecules are doing."
To explain the difference between light microscopy (which made Tsien's work possible) and her work in electron microscopy, Villa invokes a metaphor.
"Light microscopy is like giving lanterns to a bunch of people in a city. You can see where those people are, but you can't see what's going on around them. With electron microscopy, you can see the people with lanterns (a cell's molecules) and you can also see the walls and buildings of the city (the cell's structure)."
But electron microscopy has its downside. Traditionally, to be visible, cells must be prepared beforehand by drying and staining them with what Villa equates to a "thick layer of paint." However, most cells are too thick to be studied this way, and that's what makes the
Villa compares the process of studying cells (typically eukaryotic cells, in her case) at cryogenic temperatures to 'flash freezing' the cellular 'city' in her previous metaphor.
"Everything in the cell freezes in the position it was in so we can get a better look," she says. "One thing I've been studying is something known as the nuclear pore complex, which is the gatekeeper of the nucleus. It keeps the DNA inside the nucleus and away from the other parts of the cell. If we were to take it out of the cell entirely to study it, it wouldn't make a whole lot of sense, which is why we have to freeze it in place.
"With cryo-electron tomography techniques, we can create 3D pictures of the cells called tomograms," she continues. "What I do is exactly equivalent to a CT (computed tomography) scan, except the cells are a million times smaller. We can take those 3D images and look at them in the (
Villa adds that another benefit of cryo-electron microscopy is the ability to infer cellular dynamics over time, "or what we call in physics 'ergodicity.' I can look at 3,000 nuclear pores frozen at different times to infer the cellular dynamics, classify all of this information and then make predictions. We can then do a light microscopy experiment in vivo (with a live cell) and correlate what we see with the previous data we've gathered."
Villa points out that by using the
"Many kind of perturbations or phenotypes that come from disease or recovery from disease are going to be able to be examined using the
Keywords for this news article include: Chemicals, Engineering, Biochemistry, Cell Biology, University of
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