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 belly. We
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. We’re living in a new era of cell
biology, where microscopy advancements are giving biologists the opportunity to reveal
the hidden patterns of cells. What 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 worlds. We’ve 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 complexity. So 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
from. It'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 time. New 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 done. One 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 diverging. We 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
techniques. The 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 blurriness. To 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
as “guide stars” to 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 way. Using a laser guide, aberrations that distort the light’s path are revealed
and corrected by the microscope. There'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 Berkeley. This 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 microscope. You 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, right? And 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 cell. For 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 biology. We
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 works. We 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 forefronts. It'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 mean...the textbooks aren't "wrong." Like the one woman says its an oversimplification for easier learning. You're not studying to be a cellular biologist in high school, you're just getting the basics down.
neat
30 trillion cells in a human body, and each cell a virtual universe of complex biological processes.
Time stamp?
https://www.youtube.com/c/microcosmos/videos