Transcript
Peter [0:00]
So what are you
feeling, Cheryl? What are you thinking?
Dr. Nickerson [0:04]
It might be a
type of dessert, it seems like it has maybe some kind of a cream in it, but it’s
overall a drier consistency. I would say semi-sweet, not very sweet, but a
little sweet.
Peter [0:16]
If you had to use
one word to describe how you felt when that went in your mouth.
Dr. Nickerson [0:23]
I’m doing a
hyphen: semi-sweet-dry […] That’s two hyphens. Semi-sweet-dry.
Peter [0:29]
You can open up
your eyes now.
Dr. Nickerson [0:32]
It’s a moon pie!
Not too far off.
Peter [0:37]
Space, moon, pie
and we tried to get it all together.
Dr. Nickerson [0:38]
Very nice. Very
nice. I’m slower to catch up on that one. Very nice.
Peter [0:54]
Hi, my name is
Peter, and I’ll be your host for The Gastronauts Podcast. Here at Gastronauts,
we are going committed to understanding communication in the body, and in
particular, how our gut talks to our brain. In this podcast, we aim to take a
deeper dive into the mind and motivations of leading scientists and their work.
So let’s dive right in- The Gastronauts Podcast: where scientists talk about
their gut feelings.
In our inaugural
episode, we are really excited to have Dr. Cheryl Nickerson from the Biodesign
Institute at Arizona State University. Cheryl’s research focuses on the effects
of space, microgravity and physical forces on bacteria and bacterial pathogens.
She has collaborated with NASA to actually send bacteria on space shuttle
missions, and has studied how these bacteria can change to the conditions of
outer space. So welcome, Cheryl.
And the first
question I had for you, which I’m sure you get this a lot, is what drew you to
space? And how did you decide to bring space into bacterial research?
Dr. Nickerson [2:24]
That’s a great
question, and I have gotten that question before. And by the way, thank you for
inviting me to be a part of this podcast. It’s a story of you never know what
direction your life is going to take. So I was in graduate school, getting my
PhD in microbiology, and I was in my last year of the program, when a new
student came into the program, who already had his engineering degree from the
University of Texas and he came to get a PhD in microbiology. We immediately
struck up a friendship and I was instantly intrigued with how he viewed
microorganisms more as circuits. He was very analytically driven as an
engineer. And so I had a completely different perspective of microorganisms
because I came from a hardcore life sciences background and you know, there’s
signal transduction mechanisms. This is all very complex. There’s no on and off
switch that is 100%. Right? It’s shades of gray, and he was very mathematically
oriented.
And so we struck
up a friendship, which lasts to this day. We collaborate all the time; we
publish all the time; we get grants together all the time. And long story
short, for my postdoc, I went and took a position in bacterial pathogenesis and
focused a lot on the foodborne pathogen- Salmonella, and studying how it
interacted with human intestinal cells and how it interacted with animal model
intestinal tract-like mice to cause disease. And he went to the NASA Johnson
Space Center and started working in their microbiology group. So he was
involved in sampling microbes from the air and water systems in the space
shuttle on the International Space Station. And he’s an excellent microbial
physiologist.
So as time went
on, he now heads up microbiology at the Johnson Space Center. But after my
postdoc, I had learned the mechanisms of bacterial pathogenesis, especially in enteric
bacterial pathogens, and I knew how to culture intestinal cells and infect mice
and study the intestinal interaction with pathogens. On the phone one night, a
month after I got my first lab, my first tenure track position at Tulane
University Medical School in New Orleans and he had been at NASA JSC, he
commented to me on the phone in passing that the astronauts were
immunocompromised in space. So now my expertise is in infectious disease, so I
said, now hold on a minute, because that’s kind of half of the equation of
whether you’re going to get disease after you get infection. Just because you
get infection doesn’t mean you get the disease, right? It depends on the
virulence of the pathogen, the dosage of pathogen and on your immune response.
So you know something about the effect of spaceflight on half of that equation,
the immune response; what do you know, does anyone know about the ability of
the microgravity environment of spaceflight to impact the virulence of a
pathogen?
Well, nobody knew
about that, so that’s how this collaboration started. We did ground-based
experiments that gave a strong indication that spaceflight culture might impact
the virulence of the pathogen and its stress responses and its gene expression and
that led into multiple spaceflight experiments that further showed and proved
that the microgravity environment spaceflight did increase the virulence of
this pathogen and it did change its gene expression and it did change it stress
responses. We have leveraged those findings into mechanistic studies of a lot
of different ways: we found that other bacterial pathogens can use similar
signaling mechanisms to Salmonella in spaceflight, we have identified ways to
turn off that increased virulence in flight. That also led us into doing three-dimensional
cell culture under the same kinds of physical forces.
Peter [5:49]
It sounds like to
me a lot of this was bred from you working with someone who is in a field
completely different from your own. Someone, who studied engineering
background, was thinking about how systems function from more mathematical
perspective, and you’re coming in, bringing your expertise in microbiology and
virulence. And it kind of seemed to be a perfect storm: him at NASA; him
studying the immune response and astronauts and you looking a little bit at
bacteria, and how can we get the immune system to interplay with bacteria,
which is essential for us to understand how human health is going to progress.
And I was interested in teasing a little bit more into space. How did you
decide- Was it an aha moment? Like, this is the way I want to go? Did you have
any doubts? Were you thinking about other things with regards to microbial
pathogenesis, because bacteria are not frequently studied in space? It’s not
something that I think of, you know, these microscopic particles sending them
all the way in outer space? How did you make that leap of faith take that jump
to decide to study space?
Dr. Nickerson [6:48]
Well, first, I
have to thank NASA for funding those studies. Because had I proposed those
studies to NIH in the beginning, that would have been, I believe, outside their
realm of what they would have been willing to fund at that point. So I thank
them because that led to a very productive series of experiments that have
transitioned to actually being beneficial for not only astronauts in flight to
mitigate their infectious disease risk, but directly relevant to our health
down here on Earth. And a question that is just a completely logical question
is: why- and I get this with my colleagues- why in the world, Cheryl, would you
think that you would learn anything new, or advance any aspect of infectious
disease by doing microbiology in microgravity? I mean, life didn’t evolve
there, right? The one force that’s been constant in the face of the earth has
been gravity.
That’s a logical
way to have your mind wired, and my brain is wired differently. So I thought to
myself, why would you not learn something new about biological systems,
microbes, human cells, whatever, when you greatly reduce the one force that’s
been constant on this planet since it began? Life has evolved under unit
gravity; we haven’t known anything else. Why would we not think when […] you
greatly reduce that force that these emergent phenotypic properties that could
be relevant to health or disease could emerge? We’ve learned that when we study
cellular and biological systems in response to extreme environments, we learn
more information, we learn more mechanistic insight about how cells evolve and
adapt and respond. And so to me, space flight was just the next extreme
environment whose potential is just beginning to be untapped.
Peter [8:33]
This is of
interest to me, especially young in my career as a developing scientist: when
trailblazing into the unknown without really knowing what is going on, I think
there are certainly hills and pitfalls to fall into when you’re doing research.
And it’s easy to get bogged down into the weeds, and a little bit, demotivated
sometimes when your results don’t quite make sense to you after […] trying to
control for everything that goes wrong. I was wondering, how do you continue to
motivate yourself in these pitfalls? And how do you motivate your trainees and
your mentees in these situations?
Dr. Nickerson [9:08]
So first of all,
you have to be a little feisty. And you have to be just a little bit defiant,
when everybody tells you, anytime you’re trailblazing, and you’re doing
paradigm changing research, and you’re finding things that others haven’t seen,
you’re going to hear a lot of no. Embrace the no- it’s okay. As a matter of
fact, I’m someone who likes to hear no, not at first, you’ll hear no on your
grants, you’ll hear no on your manuscripts. That’s okay. If you can’t hear no,
and you can’t tackle no in this field [then] this is not the field for you. No
motivates me, because I know the work we’re doing is good because I know the
teams- I know my team, and I know my lab and I know the teams that we’re
pairing with are excellent scientists. That doesn’t mean we’re right on every
hypothesis, but hypothesis can be right or wrong. We know our science is good,
and we believe in what we’re doing. We believe in our science; we believe in
each other. And we know we’re on the right trajectory […]
I save every
rejection letter from every grant from every manuscript, and I have two of them
from the early stages. I won’t tell you what funding agencies they’re from. One
said, we have monolayers, we don’t need 3D tissue models. You learn nothing new
about bacterial pathogenesis with 3D tissue models. Okay, we can check that off
the list because that just motivates you, right? So after we helped birth that
field 20 years later, now it’s a really hot field. That’s great! Okay, but
science takes time; this is what happens. The first grant we submitted on
saying, look how physiological fluid shear forces […] just completely reprogram
bacteria to do different things than [what] we do when we grow them in a shake
flask at 350 RPM where we grow them statically in the lab, which is how most
people grow them. I got the first rejection letter from that. This is pretty
much heresy is what it says; that’s fine. Now, mechanobiology of infectious
disease is a cool thing and it’s an exciting thing and it’s good, [accepting]
the rejection letters is key. You will ultimately prevail, if you stay focused
and determined and persevere. You have to have that fight and that feistiness
and the fire in the gut. And you just do it.
Peter [11:17]
I will certainly
take that with me. Accept the no.
Dr. Nickerson [11:23]
You don’t have to
like it, but just let it motivate you. And then the good thing in the end is
you get all these exciting, new scientists coming in with new creative ideas.
And I learned a very important lesson from one of my scientific [mentors] who I
view as heroes. She always has a statement and I tell my students this all the
time. She says, “Don’t be arrogant. Because just when you think you know
everything- you don’t, arrogance kills curiosity.” I think that’s a beautiful
statement. Every scientific discipline has so much to learn. There’s so many
new discoveries to be made. One lab, one group, one team couldn’t possibly own
them all. There’s room for everybody. So be accepting and don’t think you’ve
learned it all. Because it’s not possible.
Peter [12:31]
Everything you’ve
told me so far really makes sense, right? Science is done in interesting
circumstances. It’s always done, I think, contextually- we want to see what
environment can we [create] to really stress the system and see what happens.
But I really want to get to the point that when someone calls you and says
space could be interesting and how it affects bacteria. What was your gut
reaction? [Did it] come to your head at any point where you were like, ah, this
is something that I could blend together.
Dr. Nickerson [13:00]
The whole concept
of being able to identify a new biological property, phenomenon, cellular
responses, molecular/genetic phenotype, did not seem at all unreasonable or
surprising to me to use the microgravity platform to do- it seemed to be very
exciting to use the microgravity platform to do it. But you know, it could have
been wrong; we might not have seen any differences there. The aha moment to me
didn’t come when we first got our grants that we wrote to fund that. The aha
moment came when we got our results back and we analyzed our data and [it] just
boggled our mind […] because that’s when the real excitement set in.
We were able to,
to mimic some of those findings that we saw in microgravity with some special
ways that we have to culture cells under conditions that kind of mimic certain
aspects of microgravity on the ground. They can’t mimic everything, but they
could mimic some of our key findings in flight. So we knew this isn’t just
something- we were super excited first, because I thought, wow, we’re going to
get to help astronauts stay healthy, right? We were super delighted with that,
who wouldn’t be? But then when I realized, it doesn’t make sense to me, that
bacteria would have invented or evolved the way to respond to a change in gravity.
It just didn’t make sense to me, I said, this change in force must be similar
to another physical environment that they encounter somewhere in their natural
life cycles on Earth. Because that just didn’t make sense- they evolved into
this. And it turns out, our evidence suggests they’re not responding directly
to reduce force of gravity, they’re responding directly to reduce force of fluid
shear, and at levels that are very similar to what they encounter in our
tissues. When they affect us. That, to me, was the aha moment. Then we
realized, oh my gosh, these discoveries we’re making in the microgravity
platform can translate […] back down here to help you and I, so we don’t have
to go to space. But we are basically unveiling responses that pathogens can
make when they infect our bodies, that we can’t see other ways. So now, we have
developed three-dimensional intestinal cultures that contain human tissue like
structures. They have multiple cell types that are found intestinal epithelium.
They have beautiful mucus. They have a top and a bottom; they’re beautifully
polarized. They are showing more in vivo like responses to infection. […] We put
immune cells in them. So our goal is to make those intestinal models more and
more like what’s in your body. We’ve kind of taken that line of reasoning both
from studying how bacterial pathogens respond to physiological fluid shear
forces, and also using those same forces to develop more patient defective
human tissue models outside the body to study host pathogen interactions. And
that could lead could lead to, I’m not promising, could lead to a vaccine or other
new types of therapeutics to help people.
Peter [15:50]
Yeah that is a
really interesting perspective. And I’ll think about that for a long time. And
I was wondering, you know, where do you see the space science field, the
microbiology field going in the next 10 years? And where do you see your lab
moving 10 years from now?
Dr. Nickerson [16:06]
Well, that’s a
great question. And I’m sure you will get different responses from different
people. Ultimately, I think one of the top priorities is to move away from
doing animal testing. We have to do that in my lab, because ultimately we can’t
infect humans and test everything in humans. But we have to have better more
predictive surrogate models. So, I think we can get there. By the way, a lot of
groups are making huge strides and doing something we didn’t talk as much
about, but developing human tissues and organs outside of the body with your
cells that will function and be 100% predictive to how you respond to a
pathogen. Nobody has one that’s 100% predictive yet, but we do this in our lab.
Other labs that are doing it getting more and more predictive models for
humans. That, to me is one of the major things that we must address, the fields
are moving towards that direction. But that demands a multi-disciplinary
approach of life scientists and engineers and physicists working together in
large teams, and that’s the way science works now, which is great. Our team,
your team are doing this, because no one person can be an expert and
everything. And when you bring these multi-disciplinary efforts to solve these
kinds of problems, we’re seeing that- we’re seeing this unveiling of new
approaches to solve or help understand better, what pathogens do when they infect
us. What do they do in the context of the whole microbiome that’s there that
they have to get through to infect us? How did they do this with physical
forces? How did they do this in health and disease? How do we make better models
of humans, tissues and organs outside the body that will recapitulate every
single biological, chemical, and physical factor in our bodies?
Peter [17:50]
One thing that I
really took away from what you’ve just mentioned is […] seeing something that
is so disparately related, and tying it to human health is incredible. I think
I am in awe of your enthusiasm that you gave at your talk, your enthusiasm in
this conversation, and I was wondering, does that passion really drive you in
the morning? Do you feel like it comes naturally? Or do you have to really wait
for an aha moment?
Dr. Nickerson [18:12]
It’s absolutely
natural. I’ve always said, If I do not absolutely love what I do, I will change
in a heartbeat. I am beyond passionate about my commitment to my scientific discipline
and field. It drives almost everything that I do. And my team members that I
have the pleasure to work with in my laboratory have that same fire in the gut.
So yes, we have lives outside the lab, but we kind of eat sleep and breathe
this, because we love it. You have to have that fire in your gut. When you find
what is right, […] it just drives you to do you get up in the morning, and you
can’t wait to figure out what’s next. It’s constantly a puzzle to solve. So the
passion is there; we feed off of it; we feed off of each other; we feed off of
the discoveries, because at the end of the day, it’s all about leaving this
world a little bit better than when you were here. And if any of our findings,
any of our work, any our studies translate to coming up with better or novel
approaches to combat and treat and prevent infectious disease. That’s what
we’re learning to do.
Peter [19:22]
That was a very
motivating end to our conversation, Cheryl; and I want to thank you so much for
being the first guest on The Gastronauts Podcast.
Dr. Nickerson [19:29]
It is my honor,
thank you for the invitation.
Peter [19:43]
Well, what a way
to end our first episode, Dr. Nickerson gave us a lot of advice to digest. But
what really stuck out to me is the importance of accepting uncertainty and
embracing challenge. We never really know where we’re going to end up, or how
the world will view our science. So find something that you’re passionate about
and really fight for it. I want to thank you all so much for listening, and
we’ll see you next time. For more of our content, you can follow us on Twitter @gutbrains,
or visit our website at thinkgastronauts.com. The Gastronauts Podcast would be
impossible without the incredible team that we have here. Meredith Schmehl is
our producer and the music composer. Dr. Laura Rupprecht is our social media
manager. And special thanks to the founders of Gastronauts: Dr. Diego Bohórquez
on the Bohórquez laboratory.
