Space Station Live: Protein Crystal Growth in Microgravity
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Space Station Live: Protein Crystal Growth in Microgravity

October 9, 2019

>>The next shipment of supplies for the International Space
Station is due to launch on Sunday, as mentioned, and that Dragon vehicle
will be bringing supplies for the crew members
plus station equipment and new science experiments. Among those experiments
are some focusing on protein crystal growth
including one known as CPCGHM for commercial protein crystal
growth high-density modified. The principal investigator is
Dr. Larry DeLucas, the Director of the Center for Structural
Biology, at the University of Alabama at Birmingham,
who has a history of space-based research
that includes his flight as a payload specialist on
Space Shuttle Mission STS-50, the first flight of the United
States microgravity laboratory. I spoke with him recently about
this experiment and asked him to comment on the focus on membrane proteins
in the human body. We’ll listen to that
interview now. This is Mission Control Houston.>>In our body and bacteria
and viruses, there’s proteins that exist in the
membranes of these organisms. And in the human system,
there’s literally, you know, thousands of different
membrane proteins and they play key
roles biologically such as signal transduction when something happens
outside a cell, how does that information
get imparted inside the cell to affect some other
function within the cell. They are critical in many, many
of the drugs that we develop for different diseases. So the unfortunate part of
this is that if you look at how crystallography is used,
we crystallize the protein that we’d like to
determine the structure for and membrane proteins are
probably the most difficult ones of all to get, not only to get
a crystal but to get a crystal that is of high enough quality so that we can determine the
three-dimensional structure using x-ray crystallography.>>We have to make the crystals
out of the proteins in order to study the structure
itself and learn about how it functions exactly.>>Yeah and that’s the, you
know, kind of interesting and it’s fun to crystallize
a protein but the easy ones have
been done in nature.>>How do you grow
these crystals in space and what’s the station crews’
participation or their role in growing these crystals while
they’re up there in space?>>We know from previous
experiments that the crystals grow
much, much more slowly.>>Okay.>>Because now the only
thing that gets molecules to the crystal surface is
just the natural vibration of molecules, it’s
called free interface, well it’s just called
Fick’s law of diffusion. They just vibrate, bump into
each other and make their way to the crystal but they
grow literally in order of magnitude more slowly
than they do here on Earth which allows the molecule
when it comes into the crystal to align itself more perfectly
before the next one comes in and traps it in a misalignment.>>Wow, sounds fascinating. So they form–>>That’s what we’re
comparing is without, you know, buoyancy-induced
convection, which we get here on Earth anytime
we grow crystals, by just letting the molecules
slowly diffuse to the crystal, you know, not only, we know
we can get better crystals. The question on this flight and
this is why we’re flying 100 of very difficult
proteins to work with–>>Okay.>>What percentage
will be better and how much better
will they be. We want to statistically
show, you know, once and for all the
value of doing this and we have the advantage
of a space station where the crystals will
have plenty of time to grow to their full size. So we have literally thousands
of experiments going up so that each protein has
multiple chances to try to get the very best crystals. We’re doing this
also on the ground with ground controls using
the same proteins, same batch, everything, everything’s
identical but we will not know when it returns in August
which came from space and which are the
ground controls. Everything has a bar code
and only one engineer knows, you know, what’s what. It’ll all be mixed
together for each protein. We’ll do the entire
analysis and when it’s done, only when we’re completely
finished will it be revealed which came from space
and ground. That way we eliminate
any perceived bias that a scientist may choose a
better crystal for space just to make it look better.>>One other question
that I would like to ask is why are
the space-grown crystals so important to have for
research in the disease process and the drug development? Can you explain what the
importance is for us?>>Sure. At the beginning
and I want to point that out, it’s one of the first steps, the
first step in drug development, you know after you know
the protein target, is to design a potential
drug, right, that will interact
with that protein. By having the structure,
it makes it go much faster and usually you get
a more effective drug with fewer side effects and
there are many examples, not from space but from
just ground-based research where drugs were developed using
the structure of a protein. It’s sort of like if you
had to design a key, right, that would open my
car door that’s locked in the parking lot, you know, a locksmith has a key that’ll
open all the car doors. But if I showed them the
structure of my lock, he can make a key that would
only unlock my car door. By having the structure
of the protein, it helps you make a drug
that’s more specific so it interacts just with my
protein and hopefully not others in our body because
we literally have about a half million
different proteins in our body. When these drugs
interact with proteins that you don’t want them to,
that’s how you often get, you know, unwanted side effects.>>Very interesting. Again, thank you, Larry for
taking the time to talk with me. Good luck in the continued
research and thanks a lot.>>Okay, you’re very welcome.

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