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>> Alright, so actually for me it's quite exciting
to see everyone that's here.
It's also an exciting time for space research.
I think one of the things that I wanna make sure
that at least I get across as my hopes that we are actually
at a new timeframe with actually pushing the envelope
of what we can do in space, and especially
in biological research.
If you look at, at least looking at my background
and where I came into space, you'll see that a lot
of the research that is done in space is limited.
It's been limited for multiple reasons.
But now with ISS being complete, we actually have an envelope
to open and push our understanding of space.
Next slide please.
And so my background is in evolutionary biology
and molecular evolutionary biology.
And so I always think in that gradient and flow
of how we define results and see the changes that occur.
I have the top area and you know I'll--
I saw that Howard of course discussed plans.
But usually you have the flow from the unicellular
and cell culture going to invertebrates and vertebrates.
And if you look at this progression of discussions
that we had here, of course Ruth gave her talk just before me,
and actually I think it's a good introduction to invertebrates
and why invertebrates are useful tools.
First of all, one of the key things that you'll see is
that the list is similar to what you would say is good
for ground research.
Invertebrates are small in size.
That is important because it allows you to do a lot
of different types of investigations, and we'll go
through all this as a picture.
You have a cycle, a lifespan that is very short allowing you
to do long-term studies of populations and see what occurs
as we progress through time through the changing
of variables in space.
Ease of maintenance, well you know,
in the lab it's really important to have organisms
that do not require tremendous, a lot of special equipment
and really babying around in order to survive.
In space, it's even more critical, you know,
we'll talk about all the variables,
you've heard all the variables that exist there.
The ability to maintain an organism with not a lot
of other introductions of variables
that are needed is critical to being able to answer questions
of what happens when you change the variables
as you go to space environment.
You know, we discussed rats and mice in the previous discussion
and one of the things that people use mice for is ability
to have a lot of strains and genetic variance.
What you have with invertebrates relative to vertebrates
in cell is you have that spectrum of similar pathways
so that you can actually identify what is unique
to the species versus what is more an innate strong
evolutionary background processes that exist both
on the cells and continued in through that process.
So small size, easy to maintain of course leads
to what's called large end.
And one of the things that's really important,
and I will tell everyone to do this is to go back and look
at the results that we discussed on space research and look at it
in terms of putting your statistical hat on there
and say, "Okay, what is the strength
of the knowledge that we have here?"
And really that comes up into play when you are able
to do large populations, large sample size
and of course I'll repeat this at the end,
is a repeated experiment that occurs.
The ISS currently is starting to allow us that capability,
the capability not only to do those experiments
but also to repeat them.
And of course if you ever dealt with rodent research,
there're a lot of bureaucracies with doing rodent research.
Typically invertebrates specifically do not have
as much regulations in them.
And that's an important part of using invertebrates.
Now, I put the plants down there and it's important because,
you know, the plants could-- that arrow could actually go
to the vertebrates' arrow.
But plants also have an important part
in this combination of how we look
at the adaptation processes.
Next slide please.
So, what do we study, what could we study with invertebrates?
Well, you know, there's a pull-push relationship that I
like to call and it's really, you know, you have knowledge
that allows you to do application, but application
that pushes you to understand the knowledge.
And one of the things that NASA is great about is creating lots
of new visions and each vision is either, you know,
application driven, knowledge driven and so on.
In the reality, it's a spectrum across the things,
so knowledge within invertebrates.
Well, we have a change of environment, so the first thing
that we wanna know is how do they sense a response,
what are the pathways that are important for that response?
You could learn and gain insight from responses
that have seen in cell culture.
You could gain insight from seeing them from things
that have been done on mice.
Again, it's a continuum that goes across there.
You've heard previously about the concept
of direct or indirect effect.
You know, this is one of these mechanisms
where people say is the stimuli itself
and specifically here we talk about gravity,
the one that causing the organism to respond
or it's something else in the environment.
I think it's important for us to understand that but it's--
and to try to tease that across which by the way small organisms
and plants and so on are able to allow you
in the genetic mechanisms to tease that.
But at the end of the day, they'll be that still line
across them and I will say that, you know, when I first started
in the field of space research, I read an article
that actually said, well, there is no way
that you're gonna see any differences in cells
because they're too small to actually feel it.
Well, we do see differences and those differences,
whether they are direct or indirect are yet to be resolved
but there are differences that occur there.
What are the effects that we see in model organisms?
We could study them on the physiology of the area.
We could look at mussel, immunology was mentioned.
All of those areas are affected and they're affected
because of course we're talking about a full system.
When you disrupt the system, usually you see effects
across everything and it's not something that's surprising.
It's really trying to dissect what is leading
to what changed first that occurs there.
Developmental biology, developmental biology hits both
on vertebrate and invertebrates
but when you're studying invertebrates,
you could understand some of the early on development.
We will talk about organisms and I'm trying to lead you
through this process as we hit the different models over there.
Lifespan, if we were to look at a crew member,
if we were to look at a rodent,
we wouldn't get a good understanding of lifespan
for the length of time that we have currently capable
to do research on the ISS.
With the organisms that survive, days, weeks, month, you are able
to start analyzing that across the generations.
Behaviors, another one of those areas that you could study.
Drosophila behavior, fruit flies, has been utilized
and has been observed.
There are other organisms that you could do it.
But I'll go down to the next one
which is actually something that's more to my heart
of what I would like to see
and understand is what is actually the adaptation,
what is space normal?
That is a question that still is not fully answered even
on the small invertebrate animals.
You have the short-term reaction that you see, but what happens
over a long period of time.
Does that continuously stay there upon generations,
so is that changed in effect?
This knowledge of course directly connects
with applications, whether they're applications
on the ground here or for applications for exploration.
You know, we understand that from recent studies
that you know, that at least on some microbes,
if you bring them back down and you test them,
you'll see that there is an increased virulence
in an animal model which is assumed to be transient.
That interaction of virulence is an important understanding
to occur also on space, the interaction between the host
and the parasite itself or the virulent organism.
>> You have further areas of regenerative medicine
that could be applied for in drug development.
There are models that use both from cell size
to small invertebrates to be able to test effect.
Life support, well, we heard life support in terms of plants.
Of course life support is also important in being able
to have an ecosystem that exists and also being able to test it.
So in reality, you could look at this as, you know,
you have things to-- in order to benefit exploration
but things also in order to benefit earth here.
I think the lesson that I always am fascinated and--
you know, I'm not a great study of history although I like to
and spend some time looking at why NASA was created.
And of course that is pushing education in both the knowledge
and application push of doing invertebrate studies,
pushes education, pushes the interest of people to study
and opens the window of the possibilities that exist there.
Next slide please.
So, examples of invertebrates, animals that have flown.
And I will point to the little asterisk that you'll see
in a lot of these slides.
I-- you know in this presentation I wasn't trying
to give you an exhaustive literature search
of what has been done or what are the areas.
I think what I really would like just to sort of flow
through key pluses of doing these studies but also areas
where we have to think about how we interpret the data that comes
out of space research.
So, we have nematodes and fruit flies, the common C. elegans
and the Drosophila melanogaster.
They're flown numerous times and they have a key to them
and that is that not only are they well studied
but they have a lot of homologies with a lot
of different models that have been defined and actually
in some cases have been identified
through the studies in these organisms.
You'll see that under-- other invertebrate animals,
there's a whole list of them.
There are snails, butterflies and so on.
All those are models for specific carriers
and have their key importance in what that specific model
that is being studied.
But I wanna point another one and that is something
that is really key that you will see occur with both starting
at this level and going all the way up to rodents and human is
that currently of course everybody is really
on the hot topic of what's called stem cells
and stem cell biology.
And you know, a few years ago and maybe a little longer
than that, you know, cell biology, you know,
not everything was defined through the eyes of stem cells.
But if you look at planaria, it is a great model
for understanding and following stem cell functions
within those areas.
And what is critical is the understanding not only of back
to the developmental biology area of these organisms
that really understand the pathways and the processes
by which the cells themselves change and respond to that area
within the given context of an organism.
This is why it's really important to understand
that when you look at this and Ruth actually discussed this,
is that if you look at changes within organism itself,
sometimes they're different than actually looking at the changes
within just a single cell changes.
Next slide.
So actually this is an older presentation
so I'm gonna give you, if we could go
to the next slide first.
So there is an updated presentation somewhere
floating around.
But let me just go through this and discuss a little bit
about fruit flies and Drosophila.
So I will move this to a little bit more
of a personal experience and I will say
that my first fruit fly experiment was in 7th grade.
And the beauty of that is
that of course you could grow fruit flies, get them I think
from North Carolina biologicals and you could do these types
of experiments anywhere.
But there're a lot of key differences
that you could see there.
So my evolution as I always say went from working
on Drosophila melanogaster to understanding another group
of fruit flies called Hawaiian fruit flies.
And they're really densely important for studying evolution
because you have islands and--
that are isolated and have changed across them
and you could follow the differences
in speciation across them.
But, you know, how many people have actually grown fruit flies
here in like college?
Well, you know, the typical way of transferring fruit flies
from one vial to another is of course you could tap them
so they fall or you could have a light source on top
or you could just leave them there
and turn the vial upside down.
And what you'll notice is that they climb
up because they have a gravitational response to them.
And so, we use them to help us transfer
so we don't get a full lab worth of fruit flies.
The beauty of Hawaiian fruit flies actually is
that they develop slightly different.
Their main predator are birds
and so what they instinctively do is when a predator comes
and pecks at them, they drop down and play dead.
Now of course, when I was doing this for a graduate work
and stuff, I've never thought of it as a connection to gravity.
But of course you could see that there is a direct adaptation
to the use of gravity and how you apply it.
So, Drosophila is flown quite numerous amount of times.
There are no particular references attached to this
and if you'd like references, I could definitely supply them.
What is critical about fruit flies?
Well, if you look at them,
you'll see that there is an enhanced number
of embryo so [inaudible].
So the life cycle of a fruit fly is
that basically you have the adult laying eggs into a media,
a food source, that then become a larva and then pupae,
then become an adult, right.
So they have that whole cycle across there.
And so let's look at some space flight experiments.
Well, you have more embryos being laid
by the flies as is counted.
When you look at the eggs themselves,
you see that the form of what the eggs are, and if you look
at ever a fly insect egg,
you'll see that it has a very complex 3 dimensional structure
to it.
You'll see that-- if you look at that egg,
you'll see that the components of this [inaudible] compared
to ground normal has changed.
The yolk is deposited slightly different.
But what's interesting is you have more eggs
in the environment but less of them actually hatch.
You have a decrease on both larvae that hatch.
You also see these reduced post-flight developmental
recovered embryos.
And so I'm giving you these facts
and I'm gonna give you a little bit look
at how I see a lot of this data.
You further see that, you know, if you're looking at males
to female ratio which is actually an important part
of genetics in Drosophila is that you see
that there is a change in the lifespan of the adults.
You have less mating occurring in space
and this is really something that I wouldn't have predicted,
I guess, reduces negative genotoxic response.
So I take it that most people here, you know,
since I only saw a few hands raised
about growing fruit flies, have a less understanding of actual--
of what an insect egg does.
If you think of what an insect egg does or even a chicken egg
for that fact, it has to keep a growing embryo alive
and protect it from the environment.
So in this particular area, you have a Drosophila egg
that is actually floating in a liquid sort of solid,
semiliquid food environment.
And that egg needs to provide gas exchange.
So if you actually look at an egg,
it's almost like an artificial lung that allows
that transfer environments.
All those indirect effect that you see occurring
in gas exchange and so on affect that embryo itself.
And in reality, you could see that species
of Drosophila evolved based on a depositing area
that they deposit their eggs on.
So we continue on and we see that we have a look also
in the number and type of mutations that occur in space.
And what I would say here is
that this is really useful and critical data.
It says that we have changes that occur in space itself
and that this data itself you would think,
well, flies fly around.
>> They are more resistant to the changes of gravity.
And so if this was the whole story, I would stop here.
But I would also add another thing for you to realize
when you interpret results,
and that is that space environment changes a lot
within the chambers of where these fruit flies grow.
So we also know that if you change humidity in the chambers,
you will have differences in survival of the adult pupa
to adult through there.
And so the complexity of teasing out something
that is the space environment as it's called is not as simple
as just doing a straight number counts,
but it requires a dissection of the process that you see.
So if you see this result in itself,
the next experiment should say what an environment itself
that I could control further
to understand exactly what is the switch
that is turning these results through them.
So let's move to the previous slide in this case.
And this is-- this slide has changed because what I tried
to do in this slide is actually make it very similar
to the Drosophila, and I'll tell you what are the changes
that you see in C. elegans.
C. elegans has flown less times than Drosophila.
And of course it's a hallmark organism
to understand both muscle, history of cell development
and of course aging within the aspects.
So, with the limited number of experiments, well,
we have not seen major growth morphological changes,
major development of behavior changes.
Now, does that mean there are none?
No, the analysis that was done here was really a gross video
analysis looking at it.
It wasn't dissecting every aspect of this.
There was increased rate of mutation.
That increased rate of mutation was mostly analyzed to be due
to the radiation effect rather than to the microgravity effect.
It's an interesting interaction there
that we'll discuss in a little bit.
Now C. elegans, unlike Drosophila,
are grown in multiple ways.
One of the ways is of course on a solid media
that has bacteria on it.
The other is a liquid culture that has bacteria on it.
Now, bacteria and C. elegans themselves bring together an
interesting interaction.
Now when you fly an organism into space,
you're not only looking at what the space environment is doing
on the worms themselves but also what it's doing
at the food source, so in order to go around it,
there's a media that's called CeMM
that has been used multiple times in space,
and also similar type of media on the ground
that does not require the C. elegans
to have direct food source.
It's really the nutrients in the media just go
into the C. elegans and they survive on that.
But looking at solid media versus liquid media,
what you see is that there is no tension issues that occur.
So, you know, one of the questions that come
up is will there be a difference between the tension that you see
of a worm going over a solid media?
Does that negate the effect
that you will see on space environment?
And so when you're comparing those two differences,
there have not been an issue for that that has been driving that.
What is interesting is of course is
that muscle development is altered.
Now, that is not yet fully analyzed to the details
of the path that affects it.
But it is noted that it is affected in space both
on normal wild type but also on mutants to that.
And so, I will say that if you look at gene regulation
which all the organisms, whether it's rodents, plant, cells,
all of them see up and down changes that are robust
across the whole genome.
The question of what does that mean
and what is the critical area is not fully defined
and what I would say is that some of the comparative analysis
that you could do across organisms will help define that.
So, some other interesting notes about C. elegans.
Recently in a very gross analysis,
not all of the analysis has been published.
C. elegans have been grown approximately 10 generations
in space.
That's quite important because it starts giving us the validity
to look at some of the population genetics
that occurs over time.
And so this is what I wanted to cover on C. elegans.
I will say that right now,
this model is still being developed for its use in space.
There are other groups that are using it as models for,
you know, parasite-host relationship type of experiments
but I wanted to focus on talking on things
that are fully published.
If you go to the ISS website, you'll actually see a whole slew
of experiments that are flown or currently scheduled to fly
and you'll see the realm of types of experiments
that are occurring both on--
by US investigators but also international investigators.
Next slide, well two slides forward.
Okay, so this is my viewpoint
of space environment variables and controls.
And one of the things that I will say is that, you know,
in evolution you could look at things occurring
as either gradual or something
that I think some biologists don't like but at least that I
like as a punctuated events.
Both of them are linked.
In reality, in a punctuated equilibria model,
what you have is speciation events occur due
to a dramatic change of an environment.
When I look at the process of studying space
and how it affects these organisms,
I look at the two main factors that I consider
to be disruptive in space.
And there at this point linked, they could be separated
in some models but they're still linked to a certain extent.
The beauty of ISS is it's fully not in--
you know, it's still in lower earth orbit
so it has some protection to it.
But that is gravity and radiation.
But there's a process also,
and that process also creates variables that leads to results.
That is the transportation that your organism is gonna affect--
gonna be affected by, the vehicle environment
that you have that's created.
The equipment, the equipment is really critical
because if you look at the types of equipment that we have
in space and how they operate, they're different
than what you have in the lab.
And of course lastly, sample preservation.
And so the real question is when you look
at results is do you have these processes environments?
Are they actually overshadowing critical events that are part
of your adaptive area for gravity and radiation?
And so not only how do you control for them in order
to determine them, how do you actually limit them in a way
so that you could actually see what the destructive forces are
doing in that model.
And so, that leads to controls and controls are both on orbit
and ground and they're critical for experiments in space,
because one of the things that typically is said
in evolutionary biology and that is garbage in garbage
out when you do analysis of phylogenetic trees.
And so what it is critical is that if you see results,
do you have the right controls there that lead you to say
that it is let's say gravity or radiation.
And if it isn't, then one of the terms
that usually is used is space environment.
It's the whole package that's doing those changes.
Synchronous and asynchronous controls are critical.
You can't survive on experiments
by just doing synchronous controls
or just doing asynchronous controls.
There are too many variables.
And if you're setting up an experiment, be ready to do both.
And, you know, I'm sure some people argue with me about this
but I could tell you multiple reasons why it is more important
for you to be ready to do both those experiments as you set
up your experiment design.
Next slide.
So hardware, the beauty of station is
that it is a lab in space.
It is-- currently has a lot of hardware and, you know,
I tend to be nationalistic but I like the I in ISS.
Because the I in ISS says that we're not only dependent
on US taxpayers to build the hardware that exist there.
>> We're depending
on international groups to develop hardware.
And that hardware is available for all of us to use.
There's a great website,
I mean the ISS office has quite a few great websites
and I would say you should go on there and start looking
on the types of hardware that exist.
And why do I bring hardware?
Well, hardware is critical for your experiment there.
What you gotta look when you set
up an experiment is what is your food source,
how are you gonna feed it, what's the lifespan of the food,
what happens to the food itself in space while you're doing it,
especially if you're trying to do long-term experiments.
Remember, they're all interacting together.
What is the temperature?
What temperature do you need?
Does the hardware that exist doesn't even supply you
that consistency of that temperature?
And so while you see-- you know,
the first time somebody saw these slides, well,
you have all these small letters on the side there, you know,
why are people not gonna be able to concentrate.
I'll give you some examples of them,
but what's more important is to really understand
that they have a slew of types of hardware and you need to look
at it when you set the experiment
to understand humidity, gas, what happens to the waste.
Do you wanna have passaging of the organisms?
Some hardware gives you the ability to do a gravity control.
Now, that has its own pluses and minuses
because of course there's a radius for that rotor
of the gravity, but it's better than nothing.
But that hardware itself then has its own limitations to it.
Other-- besides that, there's
of course the ability to get data down.
And I actually am one of those people that believe as much data
that I could get in realtime from space the better it is.
It is important also to understand that with--
especially with the advantages of let's say looking
at cell culture and small invertebrates is it you are
able, if you set up your experiment correct,
to avoid some of the effects of the flight up, the hypergravity
and controls and time that occurs there.
And you could almost eliminate,
depending on how you set the experiments, your samples
down because if you have the capability
to do your analysis either by genetic analysis, by video
or by on-orbit analysis, you are limiting that window
of the variables that occur there.
And so, what are hardwares that exist
for C. elegans, for Drosophila?
Well, they come from things as simple as OptiCells
which are little slide looking things.
So they're used on the ground here to grow cells
but could also fly C. elegans, and have been used
to fly C. elegans before.
They also-- you have normal Petri plates that you could fly
in these little bricks as they're called,
they actually are called bricks.
And what's key about this is
that you could literally do a lot of the experiments
with similar hardware that you have on the ground here.
So you don't have to optimize too much
with novel hardware that you have.
Drosophila has a slew of pieces of hardware
with more being developed.
EMCS which is a European-- and I guess it's US hardware
at this point, so it's a shared piece of hardware,
allows you to have centrifugation [phonetic],
allows you to have some imaging.
It also allows for habitats to be built.
So even though not all the habitats are built for it yet,
there are more to come.
Next slide.
So snakes, I wanna make sure everyone understands a snake is
not an invertebrate.
But I could give you a Drosophila example.
But this is an example of a slide that I saw in the lab
which I think it's really critical
and really nice to show.
And that is that, you know, we try so much
to tease away effects of gravity in order to understand them.
But really if we observe nature you'll see
that gravity affected them in multiple ways.
You could look at trees that have adapted to living
on tree environments, land environment
and aquatic environments.
And you'll actually see circulation differences,
morphology locations of where, you know,
the heart is across the organism.
And so right now, by the ability, the openness
of having this national lab that is ISS, what you're able to do--
and could I get the next slide please.
What you're able to do is something that's
really critical.
You know when you study how we understand DNA repair while it
was radiation that was applied
or how we understand genetic changes,
whether it was radiation or chemical modifications on things
like fruit flies and so on.
Well, what we have right now is a lab that's open, that's ready,
that has disruptive elements there that could allow us
if we set the experiments correct
to decipher new pathways, new processes.
And for me, that's really exciting.
As both an evolutionary biologist and a biologist,
I think it's a very important area.
And I will say, you know, I am--
as you can see, I cover the whole range
of different models that exist.
But if you have the capability
to do your analysis using an invertebrate,
you'll see that you'll have a lot more tools in your hands
and pockets to study changes on full system,
full organisms that exist.
I actually believe that we're gonna have a lot
of new applications coming out from further analysis on here.
So I would like-- with that,
I would like to end and thank you all.
[ Applause ]
[ Inaudible Remark ]
>> So the experiment that I mentioned
for the 10 generations, yeah, let me do that.
The question was, was there any heritable changes you ask
or any changes seen on the 10 generations across--
across the generation of C. elegans.
[ Inaudible Remark ]
>> And so, you know, this is a recent experiment
and it's actually-- and it was part
of an international collaboration
and an educational experiment that was done.
And what they did mostly is at this point,
they had some genetics, mutants of C. elegans that they flew
and they also had video observations up there.
The data that is available right now is very limited
on what they saw.
They said, on gross level, they didn't see any changes.
They do not in particular talk about the details
of further analysis and organisms
that came back to see that detail.
I think it's critical to be able to understand that.
I think one of the things that I always hid is
of course the population size that they start
with which is really important.
Because, you know, a lot of-- a lot of these experiments,
you know, until they start actually in space, go about--
I don't know, a week or 2 weeks or so on.
So most of these experiments are set
with a small starting population
and then it grows into that large area.
But those experiments are critical but we--
there's not enough detail yet.
This is why I pointed this experiment
because it's actually just the beginning of those types
of capabilities, and ISS will provide
that capability to do that.
Yeah, go ahead.
[ Inaudible Remark ]
>> Okay, you had a point first or--
[ Inaudible Remark ]
>> I thought I wasn't gonna make it and, yeah, I thought I was--
didn't have a lot of time left and since I only have 10 slides.
Well, I guess I talk a lot.
The question was actually, what is the anticipated length
of time that we expect to have in order
to see the anticipated results that we'll have?
Well, it's a difficult question to ask
because it's actually what are you being--
what are you focusing on in particular to see here.
If you're looking at to see whether let's say the amount
of muscle changes of that occurs is stabilized
across the generations over time, then you should be able
to start seeing that over your 10 generations and so
on within that aspect.
You know, it's-- really comes up to the question
of whether you think the changes is genetic
or phenotypic change, right.
>> So it's a little bit more complex than just
to quickly answer a generation of time.
I would say though if you are able to go
through multiple generations within that area
and then subculture them also
because you're changing the environment again with that,
it will start giving you an understanding
of whether there is what's called a space normal
for the physiology of that organism,
more than the genotype of-- that could go into model X and so on.
Any other questions?
Well, I'll be available after this talk
since he is trying to-- thank you very much.
[ Applause ]