Biomolecular condensates are membrane-less compartments inside cells, formed when proteins and RNA with multiple weak binding sites undergo liquid-liquid phase separation, similar to how oil separates from water. The example given is the nucleolus, a compartment inside the cell nucleus with no surrounding membrane, where ribosome-building machinery concentrates. The hosts credit Clifford Brangwynne and Tony Hyman's 2009 work showing P granules in roundworm embryos behave like liquids that dissolve and reform, and Michael Rosen's 2012 work showing proteins with multiple binding sites can self-assemble into droplets, as the discoveries behind this field.
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Brangwynne is described as based at Princeton University, Hyman at the European Molecular Biology Laboratory (EMBL) in Heidelberg, and Rosen at UT Southwestern Medical Center in Dallas.
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The hosts frame this as a repeat pick from their prior year's Nobel predictions for chemistry.
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32:04>> Chemistry. Let's talk about chemistry. >> This is an inside joke for those who are new. Um, but yes, let us proceed to to the chemistry. Noel, >> the first one, this is a recycling from last year because I do think this deserves it. Biomolelecular condensates. I'm going to say it again. These things are everywhere in biology and they were discovered by chemists for um a very good reason. The idea is in biology you need to bring particular molecules together in the right places at the right time. You need compartmentalization. Biology usually does this using membranes. For example, this outer
32:45membrane that you're seeing here, that's the nuclear membrane, and that is separating the nucleus on the inside from the outside of the cell. That's nice in ukarotes because you want to compartmentalize all of your DNA, all of your chromosomes. You don't want all of the cellular machinery running around trying to get to your DNA, right? And that's why we have the the wall around our DNA. We keep that safe. And then we have RNA, mRNA that goes outside and is kind of like hanging out with the plebs on the outside of the cell trying to make everything work. But look inside the nucleus, right? There is that blob, that orange arrow it's pointing to. >> That is the nucleosome. It's a
33:26compartment inside the nucleus itself. Some people like to call it the nucleus of the nucleus. And that's where a lot of the ribosome making machinery happens. The ribosome is the protein making factory of our cells and the ribosomes are created in that nucleosome but there's no membrane around that nucleosome. Okay, the proteins just kind of aggregate there. The ones that are important for that particular process are just aggregating there. This is an example of a biomolecular condensate. It shows how compartments can form without actual membranes around them. >> The membraneless compartment. Exactly. And the underlying physics is just phase
34:08separation. Okay. You can have proteins and RNA and they can make weak contacts and and then those things can mix with other stuff and you can kind of get you know how oil separates from water very naturally >> kind of the same way these molecular condensates can separate from other dilute phases in a very natural way. And this is a purely physically driven entropic system. Like it's not there's no active like stuff is pushing there's there's nothing active in a oil and water mixture that is pushing the oil together, right? Just the oil wants to be together and the water wants to be together because of the different chemistry. The same thing is happening here. There's different
34:48chemistry happening and that's what causes this phase separation. >> So who are the people involved? 2009 I would say Clifford Bragwine and Tony Heyman and their colleagues. They showed that these PE granules in roundworm embryos behave like liquids and those granules could accumulate at one end of the embryo >> through dissolution in just one region and then condensation in another. So it's the same substance but it would exhibit different chemistry because of its environment which was very nice. And then in 2012 Michael Rosen and his colleagues they showed how proteins with multiple binding sites could assemble into droplets. So you got a protein that's got multiple little magnetic sites where stuff can stuff can like
35:29bind and depending on the interactions you can have those proteins coales into a compartment without any um without anything on the outside. So where are these people? Regine is at Princeton University. >> Oh we're on the board baby. >> So um he is a professor in the bioengineering institute. Hyman is at EML, which is the European Molecular Biology Laboratory that's based in H Highidleberg. It's kind of like a Maxplank, but like not. I don't know if they win. I'm going to go into like what exactly that thing is, but it seems something like that. And then Rosen is a professor at UT Southwestern Medical
36:10Center in Dallas. >> Okay, so Texas is on the board. >> Yep. >> Uh okay, so fingers crossed. Fingers crossed for biomolelecular condensates. I really think that that's a because that one's another clean like sort of three people. >> Yeah. Yep. You know, >> so um >> and related to the most important academic institution, >> of course. So yeah, of all time. So it's not close. It's not close. >> That would be great. Um chemistry 2.