3D Microscopes: To boldly go…

This the miracle of being able to see what
was not being able to see before. More like Star Trek, right? It’s the age of exploration again. It’s simply incredible. So we biologists like to see how things occur
and we like to see a cell. We like see the interior of a cell. Cells didn’t evolve on a cover slip. Cells didn’t evolve in isolation. So we want to be able to study these cells
in a more natural, more physiological setting. Eric Betzig, which is the inventor of these
microscopes, had two brilliant thoughts. One was to create a form of microscopy where
you have a very thin layer of light that you scan through the sample, and that
allows you to minimize the damage to the sample. And the second problem that he found a solution
for was he borrowed a trick that astronomers use
today for their telescopes. Because how you de-blur the perturbations
you get on the atmosphere when you’re looking at a star. And we have the same problem when we’re looking
inside a tissue. With this microscope, for the first time, you
can actually observe sub-cellular details at an unprecedented level. I started to work on how cells eat, for many
years. All my life I dreamed to see this happening
in a live organism. Finally, we’ve been able to do this. Being able to observe a neutrophil just crawling
through the ear of a zebrafish, scooping up all of these food particles that
we’ve injected, that’s just mind blowing. I actually got goose bumps — my hair — I
actually still have goose bumps thinking of the moment when we actually first saw that. Being able to visualize that was just phenomenal. Cancer cells. So these are human cancer cells that have
been implanted in the zebrafish, and you can see now the cells moving along
capillaries, cells crossing the wall of the capillaries. But it’s not just a blob of the cell, like
other people have seen in the past, this time we see the details of how the cell
is sending pieces of the cell to explore their space. We’ve mapped the entire eye of the zebrafish,
and then computationally exploded the cells such that you can look at each cell as a unit,
and what you can actually observe is the changes in morphology in the context of the tissue. That’s never been done before. You can look at how all of the intracellular
compartments are dynamically changing. We can see cell mitosis, cell division, cells
kind of pushing against, beating up their neighbors while they’re violently dividing. At least that’s the impression I get when
I’m looking at cell division. Now I cannot sleep anymore. I’m up every night, trying to figure out how to
do the next thing. That’s like one of the highlights of working
at the forefront of this, because you’re one of the first people to
see these things. You’re the first person to see this, even
before your boss gets to see it. So, that’s amazing. Up to now, the science that we have been doing
is hypothesis testing. Now we can do hypothesis generating. If it were up to me I would spend the next
couple of years just imaging and exploring, because I fee like there is a lot of unknowns. We actually start to ask questions that can
push the frontiers in new directions. And then we can generate our thoughts on how
to next and test. That’s a big, big difference.

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