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  • I still remember the moment. That's something that I will never forget. The hair on my hands

  • just stood up. It's a microscopic universe within each cell. This is an unprecedented

  • view of the cellular world, where we can actually see immune cells scooping up sugars in the

  • ear of a zebrafish in real time. Focusing only on the crawling immune cells, we've noticed

  • two classes of them. One, it seems was not hungry at all, but it was very active in terms

  • of trying to figure out what the environment is. But there was another one that was slouching

  • around with a lot of food in its bellyWe can actually conceptualize, visualize, and

  • analyze the contents of each of these cellular compartments in this crawling immune cell

  • as it's scooping up its environment. That is a level of detail no one's ever seen before.

  • Were living in a new era of cell biology, where microscopy advancements are

  • giving biologists the opportunity to reveal the hidden patterns of cellsWhat we expect

  • to learn from here on out will transform our understanding of human health and rewrite

  • the textbooks on the fundamental unit of life.

  • For centuries, microscopes have illuminated

  • previously invisible worldsWeve learned how cells divide and even discovered the existence

  • of bacteria and microorganisms. These historical breakthroughs are often found in your typical

  • high school textbook. I fell in love with the cell and wanting to understand the cell

  • when I saw textbook images. I learned as I started studying the cell, that those are

  • vast simplifications of what those structures actually do and what's inside the cell. They

  • don't allow us to embrace the messiness and complexity in the cell. At research organizations like

  • the Allen Institute for Cell Science, biologists are taking a more integrated view to better

  • understand this complexitySo we at the Institute are trying to think of all the structures

  • of the cells in a holistic manner. If we don't understand which parts of the cell interact

  • with which other ones we won't ever be able to understand the true mode of action of a

  • drug, or perhaps where the side effects come fromIt's that integrated knowledge of how

  • when you pull here, you move there, that allows us to understand the cell or the tissue or

  • the organism properly. And if you don't do that you're going to miss really important things.

  • In order to see the patterns that are actually happening in the cell in space

  • and time, we have to be able to image the cell well in space and timeNew microscopy

  • is what's allowing us to image a cell in three dimensions, in their native context without

  • killing and hurting the cells, which is just absolutely needed

  • for us to just study the cell as it is. But seeing biological processes inside living

  • samples without harming them is easier said than doneOne of the ways scientists image

  • these dynamics is with fluorescence microscopy. However, harsh light from this technique can

  • cause phototoxicity, meaning the cell can get sick during the imaging session. Lattice

  • light-sheet microscopy was invented a few years ago to correct for that challenge.

  • So it's a non-diffracting beam, meaning that as the beam is traversing through the sample,

  • it's not converging or divergingWe put several of these at very specific positions

  • such that you interfere every beam with itself and then create a very thin sheet of light.

  • This fine sheet of light repeatedly sweeps over a sample in order to avoid the damage

  • that’s typically associated with other microscopy techniquesThe result builds a high resolution

  • 3D movie depicting relatively undisturbed living cells functioning over time.

  • But tissues and other biological structures surrounding cells tend to scramble the light from the

  • microscope, resulting in blurrinessTo compensate for this, the same team behind the lattice

  • light-sheet microscope borrowed a trick astronomers use to get clear views of distant stars - adaptive optics.

  • Just like how astronomers use lasers asguide starsto course correct blurriness

  • in telescopes, the process for looking at the infinitesimally small world of cells through

  • thick tissues and in living samples works in the same wayUsing a laser guide, aberrations

  • that distort the light’s path are revealed and corrected by the microscopeThere's

  • several examples where we've worked with some of the biologists, and showed them a few of

  • our samples. Their reactions have typically been, "Even though I've been studying this

  • for a decade, it's as if I'm looking at this for the first time." And that is always inspiring.

  • Even just talking about this is giving me goosebumps.

  • With such promising feedback from

  • biologists, Gokul and his team of instrumentation scientists and computational

  • experts are taking that technology one step further in a newly created imaging center

  • in BerkeleyThis is unlike any microscope you may have seen in high school. Its purpose

  • is to shed light on molecular mechanisms that are either poorly understood or not understood

  • at all. MOSAIC is the Swiss army knife microscope, as we have called it during development. And

  • the reason we've called it the Swiss army knife is because when we were trying to miniaturize

  • the adaptive optics with lattice light sheet, we realized that all of the components that

  • go into building that microscope can be repurposed to build a completely different microscope.

  • MOSAIC combines about seven to 10 different imaging modalities into one microscopeYou

  • can reconfigure or transform the microscope from one mode into another mode. Such that

  • you can interrogate your sample using different modalities.

  • We've imaged everything from live imaging, also everything that's dead as well.

  • Cells didn't evolve in isolation. Cells didn't evolve on a cover slip. The goal of this whole

  • project was to see, hey, can we create a tool that will allow biologists to be able to look

  • at their particular processes in a more physiological, more natural environment.

  • For you to have an effect in medicine and other fields, you need to understand to be able to perturb,

  • mitigate and or intervene, rightAnd that's basically what this is doing. This instrument

  • is going to be laying the groundwork in order to help understand

  • how a virus enters a cellFor instance, if you can understand

  • the mechanism by which it's fusing to the plasma membrane and then injecting

  • its contents into the cell, you now have the ability to intervene.

  • The team behind MOSAIC

  • has already built one instrument, and is in the process of bringing a second one online.

  • The next step will be opening up the instrument to biologists. Because the thing is we can

  • only get so far by ourselves. The goal is to make sure folks that have the ability to

  • have the impact, we want to make sure we break the barriers down. Whether it's access to

  • instrument time, whether it's access to computational resources or working with the computational biologists.

  • With tools like these soon coming online, biologists like Susanne are excited

  • about the next decade of cell biologyWe basically have a little alien world that none

  • of us can wrap our minds around, and it's all of these technologies that are allowing

  • us to start to do that more intuitively. Imagine a world where you could look at a cell and

  • you know what it's doing, what it has done and what it will do. That means that you could

  • collect a pathological specimen, and without too much perturbation or staining collect

  • a whole bunch of information and features just from the image, that let a pathologist

  • know something about the prognosis of the disease and the mechanism of why that's the case.

  • There will of course be more and more innovation. That's always how it works, but

  • this set of innovation is going to get translated into useful results for everyone.

  • There's literally trillions of inanimate molecules inside of cells that work together somehow

  • to create life. That's basically what thousands of scientists around the world are trying

  • to understand is how life worksWe want to watch the dynamics, the interplay between

  • these molecules in order to really understand the complexity, understand the beauty of what

  • is happening within the cells. Biology is probably one of the last human forefrontsIt's

  • the age of exploration again, but instead of looking out at the galaxies, we're looking

  • at the galaxies inside of the cells.

I still remember the moment. That's something that I will never forget. The hair on my hands

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