Host Parag Mallick chats with Professor Afshin Beheshti who is a Professor of Surgery, Director of the Center for Space Biomedicine, and Associate Director of the McGowan Institute for Regenerative Medicine at the University of Pittsburgh. In addition, Professor Beheshti has a visiting researcher appointment at the Broad Institute of MIT and Harvard and is president of two non-profits – the COVID-19 International Research Team and Kwaai. The latter aims to democratize access to artificial intelligence through the design, construction, and maintenance of a free personal AI called Kwaai.

Professor Beheshti’s research covers a range of topics focused on how circulating mirco RNAs and mitochondria impact health, but this conversation focuses primarily on Professor Beheshti’s work advancing our understanding of how spaceflight impacts biology. We cover:

1. How research on spaceflight and biology is done
2. Gaps that remain in our understanding of spaceflight and biology
3. Omics studies of spaceflight and biology
4. How studying spaceflight and biology enhances our understanding of human health more broadly

Resources

Trivedi Institute for Space and Global Biomedicine

1. New Institute at the University of Pittsburgh focused on “advancing human health through space-driven innovation”

NASA Open Science Data Repository

1. "Provides open access to biological and physical science datasets from spaceflight and ground studies, enabling data reuse for discovery and innovation."

Camera et al., 2024. Agining and putative frailty biomarkers are altered by spaceflight

1. Study on molecular biomarkers and frailty phenotypes in space

Overbey et al., 2024. The Space Omics and Medical Atlas (SOMA) and international astronaut biobank

1. An “integrated data and sample repository for clinical, cellular, and multi-omic research profiles” from a variety of space missions
2. Space Omics and Medical Atlas (SOMA) website

Corti et al., 2024. To boldly go where no microRNAs have gone before: spaceflight impact on risk for small-for-gestational-age infants

1. Explores how miRNA signatures of “small-for-gestational-age” are impacted by the space environment

Beheshti et al., 2013. Age and space irradiation modulate tumor progression: implications for carcinogenesis risk

1. Some of Professor Beheshti’s early work studying connections between spaceflight and cancer progression.

Kwaai

1. Nonprofit "building a no-cost open source Personal AI assistant"

Foreign.

Welcome back to Translating Proteomics.

Today I'm thrilled to have the opportunity to chat with Professor Afshin Beheshti, who is a professor of surgery and director of the center for Space Biomedicine and associate director of the McGowan Institute for Regenerative Medicine at the University of Pittsburgh.

In addition, he has visiting researcher appointments at the Broad Institute of MIT and Harvard and and is president of two nonprofits, the COVID 19 International Research Team at Kauai.

The latter aims to democratize access to artificial intelligence through the design, construction and maintenance of a free personal AI called Kauai.

And I'm excited to touch on all of these fascinating parts of your career, but we'll focus a lot on on his work studying how space flight impacts biology in an episode that we're calling Omics in Space.

We've got so much to cover and I'm so excited, so let's dive in.

Welcome to Translating Proteomics.

No, thanks for having me.

Excited to be here.

As, as, as we discussed and emailed.

This topic is, is so exciting for me personally because I've always wanted to study the impacts of space flight, long term space on human physiology and using multi omics methods and ever since I was a child.

And so I'm curious from your side, you've been in this area for a long time.

You were at Ames Research center before.

How did you first get interested in the topic of studying physiologic impacts of space, proteomics in space, etc?

Yeah, so I don't have the traditional career path, as you probably know.

So I mean my background's in physics, so I got a PhD in physics and I did nothing to do with biology other than as a physicist.

We were looking at, I was looking at how DNA moves through objects and modeling that as physicists like to do, like model a lot of things.

I didn't even care about the bases, the agct, no basic DNA.

So.

But physicists were stubborn.

We think we're basically jack of all trades, but master of none.

So I said why not switch over to biology after my PhD?

And that's where there's only one biology class.

So for all the younger folks, it doesn't matter what you know, you do, as long as you're passionate about it.

You get the basis and the, you know, understanding and then your creativity in your mind is the thing that will excel you, you know, into many different things.

So eventually I did a postdoc where I was in a cancer systems biology lab.

So I do a lot of different things.

And a lot of things I do is plug and play.

And in this lab, the director and the main person of the PI of the lab that was running it had a NASA grant at the time.

In addition to the cancer work I was doing, I started working on the, you know, this, I had, she had a big national program grant.

So I started working on the space biomedicine kind of idea.

Well, the focus at that time because of a grant was how does space and we could get into all the damage space does to your body, can maybe progress, you know, cancer progression and what are the risks and how can you mitigate that damage.

So early on that's how I dived in while I was still doing the cancer work.

And then eventually his, you know, my career when I was in the Tufts Medical center and then NASA Ames where I started working there, helping develop this whole omics platform that my colleague Sylvan Kass was the director in running.

This whole platform developed was called NASA genelab.

Now it's called the NASA Open Science Data Repository where all these omics stuff we'll talk about ended up ends up there that anyone could actually mine and play with.

So you know, you don't need, you don't need to go to space.

You don't need money even to go to space.

If you have curiosity, you need to go to this platform and start asking your favorite questions.

And then, yeah, ever since then I've been there.

So.

And then work on many different things as you highlight.

You know, I do a lot of AI work.

I mean personally myself, I understand the language, but I surround myself with all the smart people.

So.

And I have the approach.

The more the merrier.

So I think that's how life in general should be.

And also in science especially where you, you work with all the great people around you to really push science forward.

Because you can't do science by yourself.

Even though people might be stubborn and think that candy can.

And plus it accelerates, you know, my publications of 30, 40, sometimes even 100 people on there, you know, it's okay, you know, as long as, you know, you put aside your ego, as long as you have the science gets accelerate to a fast rate.

Why not, you know, push it forward that way?

Yeah, well, so maybe, maybe just for folks who aren't familiar with the challenges of spaceflight, both in your work you highlighted that there are physiologic Changes with both short term spaceflight and certainly we have examples like Yuri Gagarin who went, floated around for a year, came back broke, broke both his legs.

But can you just give us a quick, a quick synopsis of what are the biologic questions?

What are the biologic challenges of spaceflight?

Yeah, so I mean, most people think, you know, they watch the sci fi movies, like, oh, there's no biological risk to that, but there's this a lot.

So I'm going to make space not sound too sexy to go, but I think there's always hope.

It's not all gloom and doom.

But so when you go to, when you, you know, on Earth we very much protected from the radiation that's in space, you know, because of our atmosphere.

And then also, you know, we have bodies have adapted to gravity.

So we all know that.

So, you know, you know, a while ago NASA had defined five hazards that are happening in space that for human biology, one of it is, you know, being in isolation.

So, you know, most people are not adapted to being in a small tube with, let's say four or five other people for long periods of time.

And that could affect you mentally, but also physically and health wise too.

You know, there's a lot of people, I don't, I have some papers on this, but people, some people work on this aspect more and there's like analog astronaut missions they do on Earth where they stick four people in a room for a month, two months.

You know, so that's one aspect.

Another aspect, you know, is that being in that isolation, you get exposed to environments that you might not.

Meaning, for example, you say hostile environment.

Meaning that let's say for microbes, for example, can evolve to become antimicrobial resistance or other kinds of things that might evolve within this closed, confined environment.

Yes.

The other part is like, you know, psychological issues, you know, if you're in there, you know, it's imagine.

Maybe not so drastic, but you know.

Yes, hopefully not.

Hopefully not.

Hopefully not.

But that's the case.

You know, that's the other part where they have to train people to be like, okay, if you're stuck in this environment.

The two main things I work on is basically on the biology is the lack of gravity or microgravity, you know, very minute months of gravity, just put it that way.

And then Space radiation.

So the space, you know, microgravity is pretty self explanatory.

You go up there and you're floating around, right?

And the space radiation is not as intuitive for some people.

But you know, we can explain it.

Now where in space, you know, you got two sources or a few sources of radiation that we're not exposed to on Earth.

One is the solar particle and so the big solar flare from the sun is a high acute dose of protons and that might come in that we never experience on Earth that could, you know, be causing health risks.

The other one is the galactic cosmic race.

So there's all this background radiation that's caused by like black holes, supernovas and this.

It's just in space floating around.

The majority of that is smaller particles like protons or helium that are there.

That makes about like 90% approximately of the background radiation.

But then the rest of it is these heavier ions that could go anything from oxygen, silicon to iron particles.

Sometimes you get bigger ones out there too.

And those are, those are like bowling balls like going through your body in your cells and damaging like causing DNA damage and cause all the things that could happen and cause like tracks as it goes through your nucleus and your cells of breaks and damages happening.

Like it's been estimated if, let's say once you go to deep space, every cell in your body will be hit by one of those.

If you spend a year in space in low Earth orbit where the, you know, ISS right now and all the research being done, the old shuttle missions that happen, those were.

The radiation dose you get is much lower because of the magnetic field and due to the physics you lowered the dose of the deep space radiation coming in.

So combination of all this stuff actually speeds up.

You know, the aging phenotype gets happens quicker, you don't age faster, but all the health risk associated to does.

You had a paper last year that was on aging and frailty and focused very much on the biomarker side.

But maybe can you walk us through a little bit on so that the effects occur both at it sounds like molecular cellular scale effects, but also those cascade up to much higher order whole physiology effects.

And I think that the dramatic one that people like to talk about is that people get taller in space.

Like oh yeah, I went up to space, I came back a half an inch taller for a day and a half.

But some of these other effects are much more subtle in changes in calcium cycle reg in muscle fiber formation degradation.

Can maybe talk tell us a little bit about, about these, these aspects of frailty that are associated with, with spaceflight.

Yeah, yeah, definitely.

So I mean, the one joke, you know, people have in the field is like, well, you know, Scott Kelly, who was the twin study astronaut who went for a year in space.

The first one, he's like, oh, well, you know, he got taller, as you said, for you know, a little bit of part of an inch, you know, half an inch or so.

And he lost some weight and his telomeres, so your telomeres are, are a signal that caps on the chromosome that actually shorten as you grow older.

So his telomeres actually got longer space, although you got younger, you got taller, you're losing weight.

But no, that's not actually the case.

That's a red herring.

So.

Because when he came back, he actually got a little shorter and his telomeres actually went back to normal a little shorter and then, you know, he gained all the weight back.

Oh, all right, well, so it was a short, it was a short lived diet.

Yeah, yeah, yeah.

So the whole frailty idea is, you know, where they have this thing in the.

Clint, this is actually an idea of one of the graduates.

So, you know, my work, I say I work with a lot of folks from all grades of their career wise, from undergrads, graduate, high school, even high school students, graduate students and postdocs and beyond.

And usually the younger kids have the brighter ideas because, you know, when you get older, you get more and more narrow and your creativity might get limited.

So you want to encourage the younger folks to really explore all their good ideas they have.

So he had, his name's Andrea Camaro.

He's a now graduate student in Norway.

But he, he came up like, well, you know, in the clinic they have this thing called the frailty.

And so you come in, you have your physical age.

But of course, when you go to the doctor, they might assess you well, you might be 60 physically, but reality, some people are 50 in, in their biological age or some people are 70, you know, so they have that frailty kind of index in the clinic to save kind of assess.

You say, okay, where are you really at biologically as opposed to your physical age?

So that's the same thing.

Since, you know, in space it really accelerates your aging.

You know, we know that you're going to get your actual biological age if long enough in space, it will get long.

You'll be much older than you actually are physically.

So for example, when, you know, in Scott Kelly's book, you know, or if you talk to any astronaut, when they come Back for a long period of time in, in space for six months, they feel like they're like 90 years old.

Once they return back to Earth in space, they're feeling fine because their body's adapted to that and they don't feel that.

But when they come back they're like, oh man, I don't know how it feels to be a 40 year old now knows how to be, how instantaneously knows how to feel like it's 90.

So that frailty index, all of a sudden, you know, it's boosted way up.

So in space since this, you might not notice these changes happening since you don't have this presence of gravity and not being valuable that.

Is there a way that you could use markers like you mentioned, you know, whether it's genes or proteins.

In this case you could say, you know, proteom, because we looked at proteome data from mice studies that were done and even humans, you know, you could say, well we know from the clinical standard if these markers are up or down, then you're actually, you become more frail.

We know that in, in that paper we focused on muscle loss kind of frailty of your like sarcopenia and your muscle loss happening.

We're working now more of a more systemic frailty index for all organs that's a little more complex that we're trying to navigate through.

But with the muscle loss aspect.

Yeah, we know there's certain markers that if they are up to a certain level for proteins or, or you know, genes and, and other factors.

Yeah, you know that it's not good.

Your point of no return you get.

Frailty is going to be going to a point where the same stuff where we applied the clinical standards to the astronaut data we have and also the mouse data we have.

And then that's where we said okay, indeed.

If these set of markers are showing in space similar to clinic going.

Well, that frailty index might be indication if you start getting close to that.

Well, maybe think of mitigation strategies as their pills you could take.

Is there other things you can do?

I mean the astronauts do exercise two hours a day to help reduce that effect, which it does work, but it doesn't cure it because you know, obviously even those two hours, the constant, you know, body trying to adapt to those things are evolving.

So is, is some of it sounds like there, there's sort of two pieces to the work, just grossly oversimplified.

One is measuring what are the consequences of being in space.

And then the other is how can we, how can we Mitigate, overcome those consequences.

And it sounds like the molecular profiling is critical on both sides.

It's, it's not purely like gross phenotypic measures like weightlifting strength or it's, or lung capacity, but there are specific things that you look at as signals of muscle degradation or dysregulation of.

Or immune.

Immune subset changes, for instance.

Yeah, correct.

So, yeah, I mean physically you could gather some things, but you really need to look at the molecular profile.

So one thing that one of the main areas of research focus I work on is mitochondria, which is related to frailty.

And of course for layman, you know, kind of think mitochondria powerhouse of your cells, but creates all the energy in your body and your cells and, and long, long time ago, you know, thousands and thousands of years ago that mitochondria was a bacteria.

And it's thought, and eventually, you know, m. The body thought, oh wow, this is, this is something we should really integrate into our cells as an organelle.

And it did.

So now this is where mitochondria is a key thing for energy production.

And then now we have faults going really into the nitty gritty.

And in that frailty paper also we talked about the mitochondrial damage done in the muscle.

So when mitochondrial space was in general, what it does is micron space is suppressing due to the radiation and the microgravity.

But I think radiation causes more of a suppression to all the mitochondrial energy production that happens.

So they call the oxidative phosphorylation complexes which is involved, the main things involved for energy production in your cells.

And then I guess I understand how space radiation can lead to DNA damage and that can change, you know, cellular growth rates and things like that.

How does, how does radiation affect enzymatic processes?

Yeah, like, like you mentioned in glycolysis and Krebs cycle, et cetera.

Right, yeah, that's a good question.

So in general, like radiation does several things like, you know, but the, I mean, that is the question of how does it suppress mitochondria damage and increase glycolysis, which it's doing, and then creating a hypoxic environment and then that downstream suppresses your immune function.

So one thing is that, you know, the DNA damage done that that creates is one factor of it.

You know, mitochondria has Its own DNA.

Yeah.

So when that's a sip, you know it.

Your normal DNA man gets damaged.

There's a whole repair proteins and repair genes that come in.

Pat played to drive, you know, repair that.

Now with mitochondria, there's a whole different repair mechanism and it's harder for it to recover than your regular DNA.

So that, that's what's one of the factors.

The other part is when radiation damage happens, it causes reactive oxygen species in your body that further perpetuates mitochondrial suppression and mitochondrial dysfunction.

You know, so that's the combination of those things are I think what really is driving the mitochondrial suppression.

And that's what would then cause.

And this is something like in.

And we know in the clinic, let's say cancer for example, is a thing called Warburg effect where cancer cells would hijack the mitochondrial's energy production and increase glycolysis.

Because cancer loves sugar.

You know, basically the cancer could thrive, eat the sugar.

It takes, it takes a lot of energy to be a cancer cell.

You're constantly growing and dividing and so you need as much energy as you could possibly get.

So it takes your mind.

So that's the space is sort of doing the same thing, you know where it's.

It's not a cancer growing body, but it's through the radiation damage caused to the mitochondrial DNA and other factors, it's suppressing it.

Reactive oxygen species further causes mitochondriams.

And then this would really ramp up your glycolysis just because due to that dysregulation of biology naturally does in your cell when that's suppressed and then downstream of that, everything, you know, your immune function goes haywire after that, inflammation and so on.

Interesting.

And so the just double clicking on that a little bit in terms of immune function is.

Is that measured.

How does one measure immune function in.

In the way that you mean.

So because you don't mean things like inflammatory processes that you see inflammatory cytokines going up you.

You mean something happening with B cells, T cells and how they're behaving.

Question mark?

Yeah, yeah, both.

So, so, so, you know, good getting to your question.

I think why we're here.

The proteomics, you know, that's what people do.

So through the.

So let's back up for what kind of experiments people do.

People have sent like me have sent mice to space.

They come back, you get all their organs, tissues and stuff like that.

And then for humans like we get.

Obviously we can't dissect them.

So it's a Good thing.

Yeah.

So they have a lot less astronauts.

Exactly.

But, but with the astronauts we could get, you know, their, they draw their blood.

Yeah.

You know, or you do saliva or you get your urine.

So then you do sequencing on that.

Whether it's RNA SEQ or proteomics or lipidomics metabolome, you just go, you know, people have done all that.

We have access to data for the commercial comp, you know, companies that go and have like Inspiration4Mission.

That happened a player stun mission.

That was a SpaceX mission that happened with, with Jared Eisenman who's now the head of NASA.

He was funding those and, and he really believes in science.

So he said, you know, to my collaborate, Chris Mason is like, hey, let's work together and publish everything and really get pushed forward, like use our data, make it public.

So that's another factor where.

So for listeners, we'll put a link to that down in the comments so that people, if you want to play with actual space data, that resource is available.

Yeah.

And that's where Chris Mason developed the SOMA platform, the Space Omics Medical Atlas, where it's through his website.

He could actually go in there and type in your favorite protein or your favorite gene and see, oh, look, you know, in the astronauts, this thing's up or down.

So that you might, so the listeners might have a hypothesis that they could easily go explore on his nice, very nice platform he's created that people could play with and look at different factors.

But yeah, that's, that's where we could measure, for example, we could measure the cytokine.

So the one thing we would do is from there, and papers, in our papers, we've actually shown this like, you know, the, looked at the cytokine levels in the blood of the astronauts, how old, how do they go up and down?

So I, and the inflammatory markers.

And then you're like, okay, this could create a whole different scenario depending on which markers you look at.

From the mouse studies though, obviously then you can look at different organs and different aspects of how things are evolving.

And then the other part is, you know, with omics technology, you do a single cell, you know, or single nucleotide RNA sequencing, where that's.

And I'm sure you know about it, but let's say listeners, that's where you actually are able to look at the different, you know, T cells, B cells and monocytes and so on, you know, macrophages and K cells and all the immune cells.

And it gives you kind of the profile and how within that how the gene levels are going up and down.

Yes.

So, so then there you could actually find oh yeah, this T cell population has this kind of immune function and that means this T cell is misbehaving this way, you know, and what this B cell is doing that.

So that's, you know, overall we could do that from the blood profile.

You look at the PBMCs, the you know, per peripheral blood monocyte population and then you can see all the immune cells that are there.

And then for proteins, you know, he, he did, you could look at, you know the, in, in your body you got these extra vesicle, you know, extracellular vesicles that float around cells eject that have in there proteins, DNA, you know, and genes in there.

So someone like what, what Chris had done with the Inspiration4 crew that, you know they, they looked at, they did a proteomic and the metabolomics.

So they look at the metabolites that are floating around in the body.

Some could be freely floating in the blood, but some are packed in these extracellular vesicles.

So then you do the proteomics on that and then you really find out the profile of other proteins that are being different from, you know, when the astronauts were on Earth.

And so, you know, it's a low end number as he mentioned.

But the ways to get around that is like you have enough time points of their baseline before they went to space.

Space and then they're in space and then the time afterwards and then follow them.

How long does it take to recover?

How long does it, do things recover at all?

You know.

Yeah.

So I'd like to.

This, this is so interesting.

I, and I know Mike Snyder's lab at Stanford also had access to some of these samples and did a lot of proteomics on them.

Michael's part of the bigger team.

Yeah, yeah, it was great.

I was following that, that excitedly the studies.

But when one looks at these, the I'm curious, what is the time scale of these proteomic changes?

I imagine there's some changes that occur just because you're experiencing a lot of gravity as you're being shot up into space.

And then there are other timescales that may occur on.

I'm not sure, is it minutes in microgravity that you see substantial changes?

Are there irreversible changes that just having been in space changes you for the rest of your life?

Yeah, that's, that's a harder question to ask because.

Or answer.

I should say it's a good question because that's that's some things we do want to answer.

But so no one was really because the tough part is the same as as you mentioned, like when you go to space you experience that huge hyper gravity event.

Also when you come back you get that hypergraphy like as you said, legs broken because he was.

Yes, you know, the hypergram event.

So right now no one like to get, you know, you get the time points before they went to space and then when they so inspiration 4 for example, they, they didn't, they weren't able to collect blood in there.

But the players don, they actually are.

So eventually we're going to have data from that to show in space was happening typically from the iss, you know, for like NASA astronauts, like let's say the Scott Kelly, you know, data that's been published and been out there.

The blood collected wasn't immediately, if I remember correctly, it was like a day or two afterwards.

So you know the hypergravity effect that you're getting at, we, even if it's like two days afterwards or three days afterward, maybe the body's already got over that event because it's such a short, like what, nine minutes or something to get up there.

Right.

So that, that, that, that event you, what you really need is some kind of device that collects the samples as you go up.

So through one of our collaborators while we're trying to get a proposal to set for one of the commercial companies is like whether they take it or not, we'll see.

But for example they have an interstitial wearable device that we can put there and collect interstitial interstitial fluid as it's going up.

So then you can actually get to.

Your question is like as astronauts go to hypergravity we could actually collect interstitial fluid as it goes up, store it, run protein on that and then we'll know what that event does.

So then, and then keep doing it afterwards.

But that, so I can't really answer what happens there other than make, make hypothesis and say there's definitely some biological changes that should happen.

I don't know how well how quickly they recover from that hypergrabity event.

So but there's definitely changes that happen there and how that might exacerbate health risks, I don't know.

But you know, when they're in space, we know, you know, for long periods of time the changes that happen are like the mitochondrial damage that happens, you know what happens even in the three day mission like Inspiration four, like yeah, it got damaged.

So and you know, we know with Astronauts, when they go out after you know, a month or so or even a couple of weeks or even, you know, the short missions, they got inflammatory factors that go up, they got you know, immune factors that are being suppressed pretty quickly.

For let's say the Inspiration4 crew is a three day mission.

They went you know, about 520 kilometers above the Earth as a little elevation which is about 100 or so more above the ISS.

So they're getting more radiation because as you get closer to the Earth's magnetic field field you get less protection so you get more dose of radiation too.

So they, they, you know, when they came back we were able to get the immediate time point, you know, of their blood and everything and then they got multiple time points after that up to 80 days and then longer now but the data we analyze for those papers that goes up to 80 days.

And overall, you know, in general characterize all the papers me and Chris Mason and the team like put out about 95 of the signals came back to normal to their baseline as a 3D mention.

Keep in mind y 5% more than not.

Like one thing that might hasn't come back to normal is the mitochondrial in depending on what cell type it was, some cell types of mitochondrial suppression started going back to normal as you would hope it would, but some did not.

Like the monocyte population we're showing, oh get still suppressed now.

I bet if we wait longer, I bet it'll go back to normal because that three day mission they should, and those, that three day mission, you know, those, the, the crew, I mean they're healthy, they're still healthy but you know, I bet they, they might have felt some fatigue not or some other things associated with the mitochondrial suppression that they might not acknowledge but that was there in their body now for let's say the longer missions like Scott Kelly being in space for a year.

Yeah, he, when he came back, even inside his book it took him nine months to recover.

Right.

You know.

Right.

And usually when astronaut since spent six months to a year, you know, they usually go through intensive physical therapy to get back their strength and everything like that.

And of course that you know is related to frailty, related to the mitochondria and all the protein levels.

And this is like actually I think in Scott Kelly's book where he's talking about, you know where when he came back even his shirt was burning like touching his skin for a week like you know, you know and because it's really like inflammatory signals which we think we've shown like it's going up and, and the other part is like you know, in space you don't, you're kind of loose, you're just on your skin.

Right.

But that's a really interesting thing that we don't tend to think about is we have so many sensory inputs that gravity influences.

I'd like to just.

You've discussed a bunch a number of different types of ohms and omics data and I'd love to dig, dig around a little bit there about how these different multi omics techniques together are creating a complementary view of the biological mechanisms.

I mean you mentioned some of these are biomarkers where we're looking at secreted or circulating signals but there are also cellular patterns.

And so I'd love to hear just one or two stories from your perspective of how the multi ohmic lens and has allowed you to see things that maybe a single ohm lens wouldn't have.

Yeah, no, that's a great question.

So I mean one thing is classically when people do papers you only look at that single ohms if it's RNA sequencing or transcriptomics or proteom mainly because of costs because you know one person can only do so much.

Yeah.

Because these are very expensive assays.

Like luckily like RNA sequencing has dropped on significantly in prices, much cheaper but proteomics is still expensive in minibalomics and lipidom.

So all those omics by themselves is like showing you one piece of the puzzle because obviously our body has all these things.

We have DNA, protein, you know, even small RNA non coding RNA called micrornas and other ones that don't translate to protein but they do many, many different kinds of functions that like silencing genes and then not letting proteins being expressed.

You know the.

So there's when you look at one single ohm, let's say a proteomic, it's important.

So you're looking at all the protein levels changes.

But you might not see some proteins being expressed and you don't, don't know why.

Yeah, this could be because of these small micro RNA suppressing the genes that don't that stop the proteins from translating.

Yes.

So that's, you missed that factor.

So you might say well these certain things are related with like immune functions or inflammation or cytokines.

But the true reason like you know some of the factors that might be changing is below the protein level.

Now if you do just RNA seq, you see the gene levels is very important.

You see how different genes are changing and all that.

But then the protein, it's not always the one to one relationship from genes to proteins.

You know, sometimes a gene could be expressed very highly and the protein's not or vice versa.

Sometimes the gene's not expressed very highly but it, when it translates into the protein, protein's like blaringly high, you know, because.

Yeah, I mean I'd love to hear you know, just from, from your studies like one, one example where you, you saw this discordance and that discordance really set off a moment for you of like okay, there is an inter ohmic regulatory process at work here that you could, you could see because I think that's where we, we sort of hear generally yes, there's discordances but oftentimes there are really interesting fun mechanisms at play.

And so I'd love, I'd love it if you could share with our listeners your favorite inter ohmic regulation story.

Let me think.

I have a favorite.

But yeah, I could.

I mean one other thing I work on is microrna.

So micron is for the Nobel Prize was on last year for the people discovered it.

Well previously it was known but it was ignored.

But that was debris.

But these small RNA are about 22 nucleotides and base and they're very rigid.

They float around freely in your body.

They get in and out of cells freely but they have a protein attached to it to let doom and they can be packed in these extracellular vesicles or other things.

And, and when these micrornas what they do is they bind to hundreds to thousands of genes.

So then that, that binding itself, what it does is silence the gene and then when the gene is silenced and the protein is not produced right.

So that's, that's what happens.

So that's for me I, I think that's a. Micron is a very much the engine that might drive some of these health risks or diseases that are there or they're also for healthy functions of your body too.

So that's one thing where you know, when I dive dive down the.

You can do sequencing for small micron for a small RNA and get the whole gambit of not just the micrornas but the rest of the non coding RNAs that are small RNAs from different functions that are out there that are from you know, long non coding to peewee.

You go down the list there's tons of things that people still not fully understand but focus on the microrna part, you know, that was kind of interesting where, you know, if I just focused on the proteomic part, you know, I would miss exactly what the microns are doing.

That silence the proteins that are not expressed anymore, you know, because of the silencing of the gene, but connecting the, the micro expression to the proteins, then you start discovering, okay, if these micrornas are then to a normal level, meaning, let's say these microns are not expressed anymore and that allows the proteins to translate, meaning that explains the functionality of oh, what this is why now this immune function is dysregulated that I wouldn't have seen in the protein level, you know, because of these micrornas that are suppressing this gene that's caused the protein not to translate, you know, so.

Or vice versa.

Sometimes a microrna is suppressed that should be overexpressed in your body to silence some genes that are expressing proteins that are causing these health risks.

Yeah.

So then when you do the full omics, you're like, okay, these proteins are expressed, these, these micrones are silenced due to, let's say, space radiation.

And now these genes are being overexpressed.

That could potentially be a risk for cancer or cardiovascular disease or causing the sarcopenia that you see in your, you know, the frailty that's there.

So that interplay.

But when you do that full omic spectrum from the, and you need to do the RNA sequencing to see the fold gene profile, you see the micronutrient profile and you see the full portion.

When you connect all three together, it's really fascinating because now you see the whole interplay between all the small RNAs to the normal sized RNAs, MRNA's missionaries to actually the proteins.

And then you see that story, you're like, oh, now this story makes sense.

Otherwise things in proteins are being expressed and going up and down.

You're like, well that doesn't make sense.

Where's, where's the missing link?

And you're like, oh, it's here.

You know, it's interesting you talking about this because it feels like over the last 10 years we've seen a lot more work being done that is multi omic in nature.

And do you, do you see that as well?

That, you know, in my, my, from my lens it seems like we go back 10, 15 years, there was a lot of RNA seq done and maybe without the looking at the micro rna, without looking at the proteome, and now we're seeing more of these integrated studies.

Yeah, 100%.

I mean part of it was cost and still is cost.

But back let's say 10 years ago, the cost was substantially more.

So someone to run this whole multi omics experiment.

I don't think like an NIH RO1 grant or NASA definitely can't cover the multi omics aspect.

So then they're stuck to choose their favorite omics.

So that obviously a personal grab it.

If they're very good at proteomics, they would say I want to just do that.

And that was the thing.

But now since costs are going down like even for me if I'm writing a grant, I'm like oh, I want to make sure I do a multi omics.

And I look at the budget, I'm like okay, then I could fit this multi omic approach in this budget.

So that's the key.

And then also, you know, there's a lot more publicly available data out there.

Free data.

Right.

That's where that NASA open science data platform that was involved.

It was called Gene Lab that Silvan Costa was helm of.

You know, that was the part where now that the whole goal of that is that all these different experiments people have done, all the different omics people around put it in one platform.

Yeah.

Even though they're.

Some of them were from the same let's say Meister Synthesis space in the same organ that people ran the different ones.

And now that since it's all there because this is, you know, these are usually grant funded, you know things.

And when this grant funded the public, it should be given back to the public.

You know that's.

It makes sense taxpayers money for good, you know, after.

Yes.

So that's where now you know those platforms you can actually which I've been doing a lot as you see in my papers and other people have where now you could actually without any cost to me I could just go to the public databases like this and then incorporate the multi omics.

Even with the new data I create, I could ingest that.

So now doing the multi omics analysis is much easier because data exists out there that especially in the space field with this whole resource there we could buy, you know and then, you know, then once a more human data like you know from these commercial missions come like Chris is doing other folks.

Yeah.

And then that helps really accelerate.

I want to, I want to expand this topic just a little bit because this research is.

It's very interesting just scientifically curiosity.

It's also interesting for our future of us moving into space.

But it has practical today benefits on Earth as well.

And so can you, can you maybe talk, talk me through a little bit about how this research into space and space physiology and what is that, what is that helping us do on Earth today?

Yeah, and that's for me, one reason I do space is exactly that question.

Yeah.

So one other plug I'm going to put in is that at Pittsburgh we're actually be officially announced next week.

I expect by the time this comes out, I think it'll be already announced.

So we're launching a whole new institute called the Trivedi Institute for Space and Global Biomedicine.

So it's a whole, it's a whole new institute focused on space.

Luckily we got Trived, he's a donor who provided substantial amount of funds to get us this going.

So we got Kate Rubins, who's a former astronaut who did the first sequencing of space.

She's going to be the director.

Chris Mason is a co director still at World Corner, and Melissa and Pitts the joint.

And my center falls on the Athena.

And then Sylvan Costa mentioned he's going to start a whole synthetic biology, space manufacturing, digital health AI center underneath there.

So us four are leading the helm and pushing this forward.

So this, you know, and the reason I bring this up, because it's, to answer your question, is really key because the whole goal of our new institute is, yes, make it safe for humans to travel in space.

But the global biomedicine part, why we added that in is because everything we do has to apply to us on Earth, you know, so because space being that accelerant for, for, for diseases, anything, because the magic pill, the countermeasure that mitigates the damage done, it's going to help us on it.

So I bring up a quick example of like the mitochondrial suppression that we're seeing.

You know, all those radiation is causing this.

You know, we, I do a lot of COVID and long Covid research too.

Yes.

And long Covid we're working on a paper now is definitely a mitochondrial disease.

It's like the virus is targeting the mitochondrial suppressing that.

And even though this is the virus of radiation, the damage caused by different mechanisms, the downstream impact is exactly the same when you look at the data side by side.

So, you know, for the space work, you know, we're working on this one supplement called Campur, which is actually funded by this Japanese company, Otsuka, which is a close partner of ours, that they have this something, they're going to actually publicly release it at the end of February there and you can actually buy this so it's a nutraceutical.

So Kempferola you, you probably maybe even had for breakfast or lunch or dinner.

It's like it's found in your leafy greens like your kale, your blueberries, but they have a nice purified version of nutraceutical.

It's not harmful for people to take.

Some people absorb it better than others, you know, but that's, that's, that's, that's up to the person and their biology.

But so what the amazing results that we're working on to publish soon is that we see that indeed the campfirel through our simulated experiments you do on earth with space radiation on like these, you know, in vitro human organoid tissue models or even in my studies, we're actually able to mitigate a lot of damage caused by the space radiation by boosting because what it does is it boosts your mitochondrial biogenesis.

So it's really storing that damage.

You can't prevent the damage, but you could actually make it better efficiently repaired.

So why I'm saying this is that the same downstream mechanism damage caused, you know, with the mitochondria, if you see that in long Covid I truly think this could be a, a therapeutic that we should explore for long covet.

And there's, you know, right now Long coast, such a new thing.

400 plus million people are suffering from it.

There's no therapy like, you know, people have, doctors are trying very well to do, you know, try to cover as best they can.

But maybe it's this, maybe this could help one bit of that.

So this is like a true example of how space accelerate now for me, looking at that data and then working on this data saying, looking at side by side like look, these are the same thing.

So now this research like we're going to try to focus like we're writing grants on this and, and then also if the, maybe the company we're going to see partner with them more and say okay, let's run some clinical trials along co patients, see if it helps them.

If it does, that's awesome.

If it doesn't, at least then we found some new things to do.

But it's, you know, and there's other aspects, you know, other people are working on.

For example, since there's no gravity in space, some companies are already working on this biotech, biopharma companies where you could create the perfect crystal without the gravity.

So this perfect small molecular drug you can make.

So some companies have explored how do we make the perfect drug.

And they've done that in space.

So now they're trying to figure out can we replicate that on Earth.

If not, maybe it's just cheaper for them to work with on the commercial space companies and create, manufacture their perfect crystal drug that's going to be better binding with proteins, you know, to create.

Wow.

You know, so that's, that's another avenue that people are exploring that seems promising.

And I think maybe in a few years you might have like drug manufacturing plants, maybe not.

But, you know, it all depends on the efficacy of, of having that perfect structure relative to the cost of manufacture, factoring in the scale that's achievable in space and the transport costs.

You know, we think about the transport costs of moving something from here to Europe.

The transport costs of moving something from here to space are slightly different than from here to Europe.

Yeah, but, but the good thing is, you know, just like sequencing costs or proteomic costs have been like dropping exponentially.

Right.

Space travel costs have been also dropping exponentially.

Access to space these days are becoming easier and a lot less expensive than obviously 10 years ago.

And that's mainly because of all these commercial companies coming in the market.

Like there's Axiom Cream, space Cream, their own space station vasts.

You know, space is launching their space stations, all these companies, Star Lab.

So there's a bunch of companies that are actually providing their space station resources and then they'll, they can prove, provide accessibility to space at a cheaper cost now.

So.

Oh, that's, that's really neat.

I think this is a great segue to talk about the, the future.

And so as you imagine the future, and I'd love to hear what you see as today, what the gaps are in space biology research, and then as a, as a follow on to that, what technological advances are needed to help us get over those gaps.

Yeah.

So I mean, the, probably the biggest gap is finding the ultimate countermeasure to make you safe to travel.

So let's say if you go to Mars right now, a deep space mission like that for a year, the human's not going to be too healthy when they get there, unfortunately.

So, and they might come back, but they're going to have a lot of health risks, you know, so that's, that's the unfortunate part.

So that's the one big gap.

But there's a lot of people like me and others trying to work on the perfect countermeasure or maybe a cocktail of countermeasure you could take, or there's a mitochondrial cocktail or something else we'll figure find out and, and you know, within studying these, you know, the gaps of all these different health risks that are out there.

So you know, we know, for example, you know, there's cardiovascular issues, for example, you know, there was a New England Journal of Medicine paper that showed blood clots can form in astronauts.

That's, that could be very concerning if a long term mission you get a blood clot, aneurysm, you know, anything I could, how do you do that?

You know, so you could go on, on the list almost.

You know, every organ has a health risk associative that yes, we're learning more and more these gaps are still there for research.

So ultimately what is the systemic impact that happens and can we really have a cocktail to do that?

So one thing you haven't talked about that I was expecting you to say is that model systems on Earth that we still struggle a little bit with creating microgravity systems on Earth or microgravity equivalent systems or space radiation equivalent systems because synchrotron radiation or standard X ray radiation is, is not the same as what you experience in space.

And so some of these, some of these technologies for mimicking space feel like they need additional work.

Oh yeah, it's a very good point.

Yes, yes, that's so they, so microgravity similar experiments people do like myself, like for example in mice you got these things a high limb unloading where you hang a mouse by the tail.

It's kind of silly but you know, you're basically unloading the back weight of the, the weight of the back legs.

That's not true microgravity.

But we have to do something to simulate it with cells for example.

You know, if you want to simulate microgravity in quotes on Earth they think they have a thing called a clinostat or a random rotating vessel machine.

Whereas this machine rotates randomly displacing the gravity.

You know, you could get close and it's something to maybe have an allow to get close.

But again not a true simulation.

So that, that is a big gap.

You can never truly simulate micro for space radiation.

Luckily there's a fairly good resource there is that Brookhaven national as you mentioned, one of those high energy physics colliders, synchrotrons.

And I've been going there for a long time and putting cells and Mice in front of there and other experiments to actually radiant simulate the space radiation.

So that could get close, you know, but you're giving there, you're giving like for example, a lot of people.

What I would do is give one acute dose of accumulated radiation they might get over that period of time.

Let's say if you go to Mars, you know, what we usually do is give a half a gray, which is the, you know, the radiation of galactic cosmic ray combined beam that you go there and come back.

Yes.

Now the biology, as you know, it's a, it's a very small dose over time.

You get constantly, you know, over that whole year or year and a half trip.

So it can change low dose versus that one accumulated dose.

So that's again, yeah, that's a big gap.

So but we do what we can on Earth because as you just said earlier, it's expensive to things to send things to space and it's limited.

Yeah.

So, you know, we do our experiments, for example, getting that one big accumulated dose of radiation.

Let's say if you testing Konmers is the hypothesis is that if you're able to mitigate the damage done at that, at the lower doses, you probably will be able to mitigate that too, you know, because it's a much, much lower dose you'll get over time, you know, every day, as opposed to that whole big accumulate dose you get.

So, yeah, truly that's one of the big gaps on Earth where we, we're bound to what we can do.

And unfortunately that's it.

That's why then we have to send things to space to do experiments too.

So.

Yeah, and what about on the measurement side?

I mean, we mentioned how genome technologies have advanced a lot of.

What are the, what are the gaps that you see there or the interpretation of that data side, perhaps?

Yeah, I mean, sorry.

Yeah, I mean, yeah.

So the genome size, basically the technology that we have.

So luckily it's been getting a lot more easier to do sequencing in omics.

But if you want to do omics in space, you know, so as we know things that there's a, like Oxford Nanocore has those mini ion machines that are very small, like the size of a USB stick.

Actually, Kate Rubins was the first person that actually did sequencing in space on microbes.

So she actually swabbed, you know, the station and isolate the DNA and then threw it in there.

It's like, okay, great, we saw the profile and that's great.

So now that's unfortunately just done on.

Unfortunately just done on microbes.

But then if you want to do higher, you know, bigger, longer molecules like RNA and proteins, definitely there's no capability of doing that in space, in real time.

Right now, I imagine maybe in five, the future work, maybe five, 10 years, people are working on that.

Maybe in five years someone will have a miniaturized proteomic machine they could do in space.

You know, it's a great thing to aspire towards.

Yeah.

Because as you mentioned, like if you go, if you go to moon, you know, you collect samples and store them.

But again, samples could degrade.

Samples could still have things happen to them.

But if you're able to come up with a technology that you can do the sequencing, the omics, proteomics, genomics, all at once, real time, send the data back, that's the ultimate thing that we want to work on.

If you go to Mars, definitely you need something like that.

One thing we haven't yet managed to talk about, and I'd love to hear a little bit more about, is your work with Kauai.

Can you tell us a little bit about that initiative and what you've been doing and its goals?

Yeah, sure.

So this is actually the mastermind behind is Reza Razul, who used to be the CTO of real networks.

So he, you know, he's a friend and he's the one that came up with this.

So how do we, you know this?

As people know with AI, there's all these different AI comes like chat, GPT, open AI and so on and so on.

And the whole point is like, you know, a lot of this stuff is not owned by the person.

Like a lot of the data you ingest into the public in these AI tools is, you know, those companies have them and also it's not personalized to you.

You know, they, they do that, but it's actually the data does not owned by you.

Right.

So the whole idea of this, the vision that he had is like, hey, let's democratize AI where you will make the AI for your own personal assistance and make, make it so the AI, the data you control is yours.

It's kind of like the Linux of AI in a sense where, when Lennox first started, right.

You know, where people just gave codes and stuff like that.

Yeah.

And it's more of a grassroot public movement to do this.

So that's the idea.

And anyone can join quite a screening process, obviously, you know, but you don't necessarily have to have AI analog backgrounds.

You can have ideas to join.

So one, like one thing that I help with is more the life sciences angle is like, how can we use, how can we create the AI tools to help better inform health decisions?

For example, one paper that should be accepted soon that we worked on is like, for example, AI for chat GPT.

Some people like, what does this drug have side effects?

You know, know how accurate is that?

So in this paper show, for example, chat GPT.

50% of time it's wrong.

Oh dear, what are the side effects of aspirin?

You know, it should be fairly accurate, but half the time it might give you an answer that's not right, you know, and then so that's, if you're using that to inform your decision of side effects or other health effects, you know, that's not good.

So how can we optimize that then actually become better and also train on you?

So for example, an AI tool which can train on your medical history, that will keep it private, that's one example.

But then also the other examples of making a personalized assistant for education.

For example, they made a AI personal assistant for teachers and professors where they could ingest what they've been, you know, basically their curriculum and learn off the professor themselves internally.

And then that could be a tool that they could make available to students.

So let's say at midnight when the student's like, oh, emailing professor, hey, what's this question?

Of course, you know, the professor doesn't want to probably sleeping or doesn't want the digital twin, the AI, you know, of the professor be like ask the same question because it learned from that person their entire curriculum and it could provide an answer that could be relatively informative, the same as yes.

I mean not everything, but that's sort of the idea, you know, creating these personalized tools make it truly like an open source kind of thing that it's like a Linux was doing, you know, so that's where we're trying to shoot for and push for, you know.

That's amazing.

That's amazing.

Amazing and very important resource.

Thank you so much for making time to chat.

I think we've talked about your past and present and visions of the future and this has been so much fun.

Thank you again for joining us on Translating Proteomics today.

Yeah, no, thanks for having us.

Yeah, it was a lot of fun.

Thanks.

Absolutely.

And for all of our listeners, if you have thoughts or comments or questions, we'll post some of the papers that were referenced and also links to the data sets below.

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