Liam Holt on Crowding and Compression

Dewpoint welcomed Liam Holt for one of our virtual Kitchen Table Talks on April 29. Liam is a professor at the Institute of Systems Genetics at the NYU Langone Institute, and studies cellular crowding and the role that phase separation plays in enabling cells to manage their packed and highly complex environments.

I really enjoyed how Liam weaves together so many different themes in his research. He touches upon how there is a sweet spot for cellular crowding in terms of growth and efficiency, how cells regulate local crowding, and how tumors can overcome excessive crowding due to mechanical compression. There’s lots of food for thought in his talk, and I hope you enjoy it too.

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Mark Murcko (00:00:02):
Okay. So just as a reminder, we’ll put this out onto the web for everybody in the community to see. So Liam, thanks so much for doing this. Your work is already, I think, having a big impact on the field and it’ll be great just to hear from you any thoughts you have, current research, future directions, whatever you’d like to talk about. Floor is yours. Thank you.

Liam Holt (00:00:22):
Great. So yeah. Thanks so much for having me. And it’ll be fun to get feedback either from people live, or from people who want to see the talk and get back to me. So the amount of time allocated here is on the order of like 45 minutes, something like that?

Mark (00:00:43):
Yeah, that’s good.

Liam Holt (00:00:45):
So I mean, we can wrap up early if we need to. We’ll see how things go. So I’ll go ahead and let’s see. Share my screen. You guys seeing that? And [inaudible 00:01:09] update is available.

Mark (00:01:13):

Liam Holt (00:01:14):
Alright, so is that sharing effectively?

Mark (00:01:20):

Liam Holt (00:01:21):
Okay, cool. My name is Liam Holt and I’m from New York University and the details of how to get in touch with me are here. And it would be great to hear from people with ideas and to continue a conversation after this. What we’re gonna talk about today is the fact that the cell is this fantastically crowded environment and here’s a nice illustration from David Goodsell to kind of get that point across. And so what might some consequences of this crowding be? And one thing that’s very intuitive is that you can drastically affect the ability of molecules or organelles or complexes to move around inside this crowded environment. And this is just like if you’re driving down the FDR, not right now, right now it’s really easy to drive down the FDR.

Liam Holt (00:02:19):
But usually if you’re driving down the FDR and they close one lane of the freeway then you get this very rapid, nonlinear, slow down. And in terms of, the physics of this, when you talk to a physicist about a jamming transition, they think about frictionless spheres, which is not something that really exists in biology, these frictionless spheres, they jam it, volume fractions of 60-ish percent. But in biology, like I said, it’s very, very different. All of these molecules in the cell are interacting and colleagues downtown at NYU, so Jasna Brujic here, she has looked at just simple spheres that are made of polystyrene and they have those sticky patches on them so they can interact…

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