11/30/2018

The Asymmetrical Self

9:37 minutes

actin gliding
A comparison of actin gliding powered by the Myo1D protein, left, and Myo1C protein, right. Notice the difference in the gliding patterns. Credit: Michael Ostap Lab

In nature, true symmetry is rare. The Earth is slightly squashed, some birds’ beaks tilt to the right, and even the two wings of a butterfly will be slightly different.

Inside the human body, the story is more twisted. Our hearts are on one side, our lungs are different sizes, our organs are strange, lopsided shapes, and even our cells aren’t spherical or uniformly organized.

But how does an embryo develop from a uniform ball of cells into an asymmetrical organism? New research published in Science points to one possible mechanism: a protein that can cause the cells of fruit flies to tilt and their tissues to twist. Michael Ostap, a professor of physiology at the University of Pennsylvania in Philadelphia, explains how this simple process could lead to the kinds of asymmetry that our body plans depend on—and why it matters.

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Segment Guests

Michael Ostap

Michael Ostap is a Professor of Physiology in the Perelman School of Medicine at the University of Pennsylvania in Philadelphia, Pennsylvania.

Segment Transcript

IRA FLATOW: Think of something symmetrical in the natural world, meaning you can reflect them in a mirror and they’ll look the same. For example, the two wings of a butterfly, the two sides of a leaf, the two sides of your face. But surprise, surprise, many things you’ll encounter in biology are built on a foundation of asymmetry, even down to the cellular level. Your tissues tilt and twist and take on shapes that no amount of reflection will make into mirror images. 

In fact, your heart is solidly on the left side of your chest, right? And even your lungs are two different sizes. Where does this come from? Researchers writing in science are on the trail of one mechanism, a single protein that seems to twist cells in fruit flies’ bodies until the entire animal is warped. Here to explain is Dr. Michael Ostap, a professor of physiology at University of Pennsylvania’s Perelman School of Medicine in Philadelphia. Welcome to Science Friday. 

DR. MICHAEL OSTAP: Thanks so much for having me. 

IRA FLATOW: Drill down for us. What are the different ways organisms might be asymmetrical? 

DR. MICHAEL OSTAP: OK, so if you take our body and you look at us from the front, as you just said, we have this asymmetry. You put a mirror down the side of us, the left looks like the right. But as we go a little bit deeper, you will see there is an asymmetry. As you just said, the heart is on the left. The organs are scattered around. But what’s really interesting is, even though it’s asymmetric, we’re all the same. Except for very rare instances, we all have this same type of asymmetry. 

IRA FLATOW: Interesting. And I understand there’s this term chiral, another kind of asymmetry. How is that special? 

DR. MICHAEL OSTAP: So the chiral is if you have a similar shape, but an opposite orientation. And a really good example is if you consider your hands. So your hands are symmetric, as we just talked about, but you can’t put your right hand in the left-handed in glove. So this is this chirality. So something in biology happened that allowed this chirality to occur. 

IRA FLATOW: Let’s talk about the fruit flies. Take us to the fruit flies. What is this protein doing to them? 

DR. MICHAEL OSTAP: So it’s actually setting up some of this chirality. So if I can take a second, I just want to tell you about this previous experiment that our collaborator Stephane Noselli did, in order to address this question of chirality. So in fruit flies, they’re symmetric, just like we are. They have left and right sides. 

But if you look at their internal organs, you’ll see that some of them have a twist. For example, the reproductive organs and the intestine has a really well defined directional twist. And so the Noselli group wanted to ask, what is responsible? Can we identify a gene that’s responsible for giving this specific handedness, this specific twist? 

So they used the fruit fly to start modifying genes to ask specifically which ones are important for making this twist. And they discovered a molecule called Myosin 1D. So that if you knocked it out in the fruit fly, all of a sudden these organs would have the completely opposite twist. So this particular gene, the protein expressed by this gene, gave a specific chirality. 

IRA FLATOW: To the fruit flies? Do we have anything similar to that in us? 

DR. MICHAEL OSTAP: We do. We do have myosins. So myosin is my favorite protein. So it’s a really incredible, literally a nanoscale molecular motor. It’s a protein that interacts with the cytoskeletal filaments and is able to walk along these internal filaments inside your cell, and transport membranes and other components. And we absolutely have this myosin. 

IRA FLATOW: So are they twisting and turning our cells, the myosin in there? 

DR. MICHAEL OSTAP: So it is. 

IRA FLATOW: That’s cool. 

DR. MICHAEL OSTAP: So where my lab came in is we asked, my research specialist Serapion Pyrpassopoulos asked, OK, this myosin is a protein we know. Can we actually learn something about this molecular motor that tells us why this chirality could emanate from it? And so he did an assay where he looked at the gliding of these cytoskeletal filaments. 

He put the protein down on a cover slip and he labeled the cytoskeletal filaments, and what he saw was that these filaments turned in circles. So this particular myosin gives chirality to the cytoskeletal filaments, which is really quite amazing. 

IRA FLATOW: So they’re like little motors? 

DR. MICHAEL OSTAP: They are exactly motors. They’re little transporters. They’re nanometer-sized transporters that use chemical energy to do mechanical work. They’re very similar to the proteins that make your muscle fibers contract. 

IRA FLATOW: Wow. I’m Ira Flatow. This is Science Friday from WNYC Studios, talking with Michael Ostap, professor of physiology at the Perelman School of Medicine in Philadelphia. Why is asymmetry so mysterious if it’s also so common then? 

DR. MICHAEL OSTAP: It’s because the asymmetry occurs very early in development. And it’s been very difficult to figure out, in different cell types, where the asymmetry comes from. And so because of that, this current paper addressed that point correctly. So the question is, can this particular myosin, this Myosin 1D, can it make a tissue that’s not normally chiral chiral? 

And so what this paper all is all about is taking this protein and expressing it in the epidermis, just at the outside skin layer of the Drosophila larvae. And what happens is this non-chiral tissue all of a sudden twists. So this whole body of this fruit fly is now twisted. And in fact, if you take the protein at the gene, and you express it in another organ– for example, the trachea, the breathing tube of the Drosophila– if you just express this protein in the trachea, that as well will twist. 

IRA FLATOW: Well, we need to call it the Chubby Checker protein, I think. 

DR. MICHAEL OSTAP: OK. 

[LAUGHTER] 

IRA FLATOW: So everybody can get with it. Could we harness this protein in some way, besides just making weird looking fruit flies? 

DR. MICHAEL OSTAP: Well, could we harness it? Well, what we can do is we could study it in a more complicated system. And people have been doing that. So the Drosophila system is a bit different than a vertebrate system. So chirality occurs in a slightly different way in a human or a mouse or a chicken. And there’s another molecular motor called dynein, which I guess I’ll say is my second favorite protein, that causes these hairlike projections from cells to twist and scatter growth factors around the inside of a developing organism. So it turns out, though, that this Myosin 1D may be important for the establishment of those cells that have those other types of dynein twisting mechanisms. 

IRA FLATOW: So where do you go from here? OK, we’ve got your two favorite proteins down now. Where does the research head? 

DR. MICHAEL OSTAP: OK, so we know the genes. We know the gene products. And we know some of the cells that they’re in. Now the really interesting question is, how are they actually working? 

So I’m a biophysicist and I’m really interested in the specific molecules and how they interact with their filaments and how they’re controlled. So how does this molecular motor that does twisting affect cell morphology? So just the cell shape. How does this protein affect the cell shape that allows these larger order twists to occur? 

So I’m just really interested in getting in there and dissecting the cell and asking when these myosins make force, what are they interacting with? And we already have some really nice clues that these motor proteins are binding to proteins that connect cells together. So these motor proteins may be biasing how these cells connect and causing just the overall large cell sheets to twist. 

IRA FLATOW: Wow, just like a sheet, a sheet of molecules, or sheet of cells together, they just twist them around. 

DR. MICHAEL OSTAP: That’s right. So if you look at a sheet of normal epithelial cells, they kind of look like a bunch of hexagons that are packed together. Really beautiful. When you overexpress the Myosin 1D, these hexagons all distort. Like you pull from opposite corners, and form the shape. So that deformation is allowing this overall epithelium to change its shape. 

IRA FLATOW: Now I see why you find– 

DR. MICHAEL OSTAP: [INAUDIBLE]. 

IRA FLATOW: Now I know why– I see why you find this interesting. It is fascinating. Thank you, Michael, for taking time to be with us today. 

DR. MICHAEL OSTAP: Oh, it’s great being here. Thanks so much. 

IRA FLATOW: You’re welcome. Michael Ostap, professor of physiology at the Perelman School of Medicine in Philadelphia.

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