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Enzymes that assemble into droplets can speed up cellular reactions
Within the past decade, biologists have discovered that one strategy cells use to keep their contents organized is a phenomenon known as phase separation.
Similar to the way oil forms droplets that float in a vinegar solution, proteins inside cells can phase separate to form highly concentrated droplets that keep them organized within the cell. In a new study, MIT researchers have now shown that this droplet formation is critical for controlling the function of a class of enzymes called kinases.
The researchers found that condensing into droplets optimizes the biochemical conditions needed for kinases to catalyze reactions, allowing them to more rapidly activate cell signaling pathways. In some cases, droplet formation can even change which reactions the kinases perform.
“Many biological molecules have this propensity to spontaneously separate. We were really interested in asking, if we have these kinases forming droplets, what is the consequence of that in the context of signaling?” says Lindsay Case, an assistant professor of biology at MIT and the senior author of the study.
Learning more about how these droplets form could help researchers design drugs that target kinases, some of which can be overactive in cancer cells.
“Understanding the chemistry of these compartments, and what molecules go into them and what molecules don’t go into them, could help us design drugs that better localize to their target of interest,” Case says.
Nicholas Lea, an MIT graduate student, is the lead author of the paper, which appears today in Cell Reports.
Forming droplets
Since her days as a graduate student, Case has been studying how the physical organization of molecules inside cells affects their function. As a postdoc, she began studying how phase separation might affect a signaling pathway that allows cells to sense when they’re attached to their environment, so they can respond appropriately.
Some of the proteins in this pathway are kinases, which activate other proteins by adding phosphate groups to them. Kinases can also activate themselves through a process called autophosphorylation.
“Inside of the cell, you have these kinase molecules that are responsible for carrying a signal through the cell, and we know that the organization of these molecules changes. When the information is present, they’re organized in a different way than when the information is not present,” Case says. “We think that having the right molecules in the right place is incredibly important for the right biochemistry to occur.”
Phase separation is one of the methods that cells appear to use for this organization. The most familiar example of phase separation can be seen in a salad dressing, where oil forms droplets to minimize contact with water-based vinegar. Proteins can phase separate when they are highly concentrated, leading them to self-assemble into dense droplets floating in the cell’s cytoplasm.
Case hypothesized that this phase separation, which brings kinases together at a high density, might help cells to boost the enzymes’ activity because they are more likely to bump into and phosphorylate each other.
In this study, Case and Lea set out to test that hypothesis, focusing on an enzyme called focal adhesion kinase (FAK). This kinase, which becomes activated when cells attach to their surrounding environment, activates pro-growth and pro-survival signals. In cancer cells, this signaling pathway can go awry, allowing cells to proliferate even when they detach from their original locations.
Scientists already knew that when cells are properly attached to their environment, that adhesion signal causes FAK to accumulate at the cell membrane. In the new study, the MIT team mimicked that effect by overexpressing FAK in cells. These cells were floating freely in a solution, not attached to any surface. Even so, the high concentration of FAK caused the kinase to phase separate into droplets, which turned on the pro-growth signal.
“It was surprising that just by condensing this protein into a droplet, you can actually turn on a signaling pathway that should be turned off,” Case says. “If FAK concentration is too high, you’re always getting these droplets and you’re always signaling, regardless of what the receptors that are supposed to be controlling this are doing.”
The findings suggest that in cancer cells, overexpression of FAK may lead to phase separation, which then helps to drive cancer progression and metastasis.
“It may be that for some kinases, you’re not supposed to form these droplets in the cytoplasm because it leads to this always-on signal, and then the cells no longer listen to the information coming from the environment,” Case says.
Interfering with FAK’s ability to form droplets could offer a new strategy for cancer drug development, she says.
Controlling reactions
The researchers also studied two other kinases, Mst2 and Abl. They found that these enzymes could also phase separate at high concentrations, and that this increased their activity. While phase separation of FAK in the cytoplasm may occur only in cancerous cells, for Mst2, it appears to be a strategy that healthy cells use to control a signaling pathway called Hippo, which promotes cell growth and survival.
Additionally, for both Mst2 and Abl, the researchers discovered that phase separation can lead the enzymes to phosphorylate additional targets, which may lead them to activate different signaling pathways.
“It’s not just that you’re getting faster phosphorylation, but in those cases, the patterns of what is actually getting phosphorylated were very different inside of the droplet compared to what might be happening in a non-droplet context,” Case says. “The kinase is able to phosphorylate amino acid residues beyond the set of canonical sites that have been described before.”
The researchers also found that when these droplets form, they attract high concentrations of ATP, the molecule that kinases use as a source of phosphate. This occurs because kinases tend to contain floppy sections containing many positively charged amino acids, which attract negatively charged ATP.
Using a machine-learning model, the researchers predicted that about 45 percent of the 500 kinases found in human cells would have the ability to form droplets like those seen in this study. Those kinases were also more likely to be highly positively charged, which could help them to recruit ATP into the droplets.
In future work, Case hopes to explore the possibility of designing drugs that could mimic ATP’s ability to be attracted into droplets within a cell, which could help reduce negative side effects of the drugs.
“By localizing drugs to the compartment where your target localizes, that could reduce off-target effects by concentrating the drug with the target of interest and reducing interactions with other molecules,” Case says.
The research was funded by a Searle Scholars Program Award, the U.S. Air Force Office of Scientific Research, the National Institutes of Health, the Royal G. and Mae H. Westaway Family Memorial Fund, and a David H. Koch Graduate Fellowship.
Welcome New EFF Executive Director Nicole Ozer
EFF welcomes our new Executive Director Nicole Ozer today!
Nicole is a legal expert on privacy and surveillance, artificial intelligence, and digital speech who previously served as the inaugural executive director of the Center for Constitutional Democracy at UC Law San Francisco. From 2004-2025, she was founding director of the Technology and Civil Liberties Program at the American Civil Liberties Union of Northern California.
Nicole has long been a partner of EFF’s in the fight to defend civil liberties in the digital world. Many of us already know her, and she’s basically as close to EFF “family” as someone can be without actually having worked here.
Over her more than two decades leading public interest technology work, Nicole has:
- spearheaded passage of the California Electronic Communications Privacy Act – working with EFF to enact the nation’s strongest electronic surveillance law, requiring a warrant for government access to electronic information;
- modernized California law to protect reading records in the digital age by helping, along with EFF, to craft the Reader Privacy Act, requiring a “super warrant” for government access;
- created a groundbreaking model law for local democratic oversight of surveillance systems which inspired 25 laws across the country that help safeguard the rights and safety of more than 17 million people;
- litigated civil liberties cases, including work with EFF on the NSA cases, and drafted influential amicus briefs on technology issues at all levels of state and federal court, including the U.S. Supreme Court and California Supreme Court; and
- developed multi-year campaigns to strengthen the anti-surveillance policies related to social media surveillance and face recognition of major technology companies and foster stronger privacy and free expression protection for billions of people worldwide.
And that's just the TL;DR! You can read more about her bona fides here.
EFF’s work to ensure technology supports freedom, justice, and innovation is more urgent than ever. And with Nicole’s decades of leadership in public interest technology work, EFF is poised to be stronger than ever to meet this moment and build for the fights ahead.
Nicole succeeds Cindy Cohn, who has been with EFF for more than 25 years and served as executive director since 2015. Cindy is leaving EFF later this month – not to retire, but to find a role that puts her back in the courtroom doing what she does best: suing the government! She’ll still be part of the EFF community.
We are living digital lives, using technology to connect, communicate, and mobilize for change. And we need you in these critical fights to defend and advance rights in the digital world – so join EFF today, and sign up for our EFFector newsletter to make sure you’re updated on the latest EFF news including upcoming events to help you get to know Nicole.
Welcome Nicole!
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Friday Squid Blogging: Another Squid
Someone named “Squid” seems to be a “West Country legend.”
As usual, you can also use this squid post to talk about the security stories in the news that I haven’t covered.
One Step Forward, Two Steps Back: CA's AB 1856 Exempts Open Source But Expands Age-Gating
After public outrage, California lawmakers are moving closer to exempting open-source operating systems from the sweeping age-bracketing regime mandated by last year’s Digital Age Assurance Act (AB 1043). Nonetheless, the current bill still jeopardizes internet users’ speech, privacy, and security.
While the open source exemption, if passed, would improve the law, the remaining amendments proposed by AB 1856 would require all web browsers and websites to request and collect users’ ages. This is an expansion of last year's AB 1043's age-bracketing system that compounds its constitutional harms to users’ speech, privacy, and security. As AB 1856 moves on to the Senate, EFF will continue fighting for amendments that reduce those harms.
AB 1856 Extends AB 1043’s Age-Gating RegimeLast year, California passed AB 1043, which requires all operating systems and app stores to create age-bracketing systems that segment users based on their ages. As we’ve written, that regime is a recipe for censorship: it creates unnecessary and unconstitutional barriers to accessing lawful online speech, threatens our right to anonymity, and pressures online services to collect troves of valuable and sensitive user data. On top of that, A.B. 1043’s wide-sweeping compliance burdens impose disproportionate harms on the open-source ecosystem that underpins much of the modern web.
Given these flaws, lawmakers introduced AB 1856 this year as a supposed “clean-up” bill for AB 1043. But instead of sticking to fixing AB 1043’s unique and serious harms (like its impact on open-source operating systems), AB 1856 also expanded the regime even further—extending its age-bracketing requirements beyond operating systems and app stores to browsers and websites.
EFF opposed AB 1856 on two grounds, which we explained in our opposition letter to the Assembly:
- The harms that age-gating regimes pose to users’ speech, privacy, and anonymity; and
- The disproportionate harms that this particular regime imposes on open-source developers.
On May 28th, AB 1856 passed the Assembly in a nearly unanimous vote (68-1).
Before that vote, however, AB 1856 was amended to relieve the compliance burden on open-source operating systems. This is a meaningful improvement and a welcome relief for open-source developers, who have been loud and clear about how much of an existential threat A.B. 1043’s age-gating mandate would pose.
The new exception reads:
“Operating system provider” does not mean a person or entity that distributes an operating system or application under license terms that permit a recipient to copy, redistribute, and modify the software.”
EFF understands this amendment to exempt open-source operating systems from the requirement to collect and transmit users’ age-bracket data. That is a definite win for open-source developers. The bill is narrower now than it was before, and lawmakers clearly responded to concerns raised by EFF and the broader open-source community.
Some important questions still remain—for example, it is unclear how the law would apply when an open-source operating system is incorporated into a commercial product or service. And, given the structure of where the exemption is placed under the “operating system provider” definition, lawmakers could stand to clarify that the exemption applies to open-source operating systems and applications.
Nonetheless, that ambiguity aside, this amendment does substantially reduce the threat that AB 1043 could have on many open-source developers.
AB 1856 Still Expands the Problematic Age-Bracketing RegimeDon’t get us wrong—if this bill passes, we will be very happy that AB 1043 does not pose nearly the amount of harm to our friends behind open-source operating systems. But even after these amendments, EFF remains opposed to AB 1856 because it ultimately expands California’s sweeping age-bracketing framework far beyond the original scope of AB 1043.
In AB 1856 and its amendments, the Assembly failed to address the core problem with AB 1043’s age-bracketing regime: mandated age-gating systems threaten users’ speech, privacy, anonymity, and security.
Even after these amendments, EFF remains opposed to AB 1856 because it ultimately expands California’s sweeping age-bracketing framework far beyond the original scope of AB 1043.
Even though AB 1043 does not explicitly require companies to perform age verification, it nonetheless imposes a liability structure that strongly pressures companies to verify users’ ages anyway. In practice, that could lead to more ID checks, more biometric scanning, more invasive data collection and risk of breach, and more barriers to adults’ and young people’s lawful speech.
In fact, instead of narrowing AB 1043’s wide net, AB 1856 expanded it to add browser providers and website operators to the list of entities that must comply with its age-bracketing requirements. This dramatically broadens the scope of AB 1043 and pulls more services, developers, and users into an anonymity- and privacy-destroying data collection framework that has not yet been implemented or evaluated. The result would make it nearly impossible for regular internet users to avoid AB 1043’s age gates.
The Fight Moves to the SenateOn those grounds, EFF will continue to oppose AB 1856. Though it has passed the Assembly, the fight is not over. As the bill moves through the Senate, we’ll continue to push for amendments that actually “clean up” and narrow the scope of AB 1043, and offer more protection to users from the harms of age-gating systems.
Photos: The Class of 2026 turns the page
Cheered on by the greater MIT community, members of the Class of 2026 were honored this week for the hard work that earned them their newly minted MIT degrees.
The 2026 Commencement celebrations spanned three days filled with degree ceremonies, receptions, and reunions, at locations spread across campus. The weather ranged widely, but spirits remained high even as Wednesday’s sunny, selfie-perfect weather gave way to some rain later in the week.
Advanced Micro Devices chair and CEO Lisa Su ’90, SM ’91, PhD ’94 gave the Commencement address at the OneMIT ceremony for all graduates, held Thursday. Undergraduates crossed the stage during their own ceremony on Friday, and throughout the three-day celebration, MIT’s five schools and the MIT Schwarzman College of Computing each held ceremonies to recognize their graduate students. Friday also kicked off a weekend of Tech Reunions.
As Institute Professor and School of Engineering Dean Paula Hammond told graduate students earning degrees from her school and the MIT Schwarzman College of Computing, “What makes MIT special isn’t just what happens underneath this dome. What makes MIT special is you.”
The following photo essay provides a snapshot of MIT Commencement activities throughout the week. (Additional recaps/photo collections are available for the School of Architecture and Planning, School of Engineering/MIT Schwarzman College of Computing, and School of Humanities, Arts, and Social Sciences).
Alejandro Aravena urges School of Architecture and Planning graduates to lead with kindness, honor the truth
What distinguishes the MIT School of Architecture and Planning’s Class of 2026? According to faculty and staff across the school, it’s their hearts.
“They’re big-hearted in the way they deal with each other, with their work, and with the world,” said Hashim Sarkis, dean of SA+P, in his opening remarks at the school’s 2026 Advanced Degree Ceremony. As a nod to the class’s generosity, Sarkis announced the creation of the Class of 2026 Scholarship fund to help support incoming students.
“Education is a right, not a privilege, and this fellowship brings us closer to our goal of giving this right to every student and becoming tuition-free as a school,” said Sarkis.
The news was met with joyful and sustained applause.
The SA+P Class of 2026 represents graduates from each of the school’s departments: Architecture; Urban Studies and Planning; Media Arts and Sciences (MIT Media Lab); and the Center for Real Estate. The 206 graduates — including six with dual degrees — represent nearly every corner of the globe. Fifty-seven percent are from the United States, 10 percent are from China, and 5 percent are from India.
This year’s speaker was Alejandro Aravena, a celebrated Chilean architect whose credits include curating the 2016 Venice Architecture Biennale “Reporting From the Front,” and being awarded the Pritzker Prize (2016), the most prestigious award in architecture — for which he currently serves as jury chair. Aravena leads the architectural firm ELEMENTAL, based in Santiago, Chile, with work that spans a variety of public and private projects developing novel approaches to community engagement shaping how architects and policymakers think about the built environment.
Sarkis said Aravena speaks eloquently to the breadth of fields represented in SA+P, and to the school’s values, “[from] the power of architecture and design to enable society to his innovative models of social housing to creative approaches to community engagement — be it in emergency planning after earthquakes, or in institutional buildings — and to putting architecture front and center in the discussions around the new constitution of Chile.”
Addressing the students and their guests, Aravena shared a series of vignettes that illustrated a world at a “tipping point.” Will it land on the side of civilization, or barbarism?, he asked. One story was of his firm’s work on a project in Chile where his team encountered the “law of the jungle.” During a slum-upgrading project, two social workers from the Ministry of Housing were stalked on their way home by hired killers. With knives at their throats, they were warned never to return if they intended to interfere with the territorial power of organized crime. The message was clear: Come back, and your families will pay the price, he said. A more recent project — building a hospital for victims of sexual violence linked to the armed conflict in Colombia — had the architects questioning the level of violence that people inflict on each other.
If the “law of the jungle” was going to be the new normal, Aravena said, he needed to understand what that meant. Measuring the sizes of a prefrontal cortex — the brain’s command center that controls emotions, complex decision-making, and executive function — within the animal kingdom, humans have the largest capacity for emotions and behaviors.
“The history of humanity and the evolution of the human condition is connected,” he said. “It’s moving in the direction of the prefrontal cortex. Yet, somehow, we’re turning backwards.”
Aravena suggested the students use their newly acquired skills to work on projects that matter to others, and not to just themselves.
“Leveling the playing field, having more people behaving and coexisting in a more even playground, is very bad news for predators,” said Aravena. “Try to use this knowledge and wisdom you have and the training you have received in common interests, and not in just the self. Let’s try to bring back decency. Let’s try to bring back kindness. Let’s try to bring back honoring the truth. And let’s join forces to make the coin fall on the most human possible side.
“Class of 2026, together, let’s make the prefrontal cortex great again,” Aravena concluded.
Scene at MIT: A nanoscientist graduates with her very good boy
“I’m originally from Moorestown, New Jersey, a suburb of Philadelphia. While my degree is in chemical engineering, I consider myself a materials scientist, and I’m passionate about using innovative materials to propel next-generation technologies. When I started my bachelor’s degree at Cornell University, I was introduced to polymers and nanotechnology and even got to partake in some meaningful industry experiences in the medical device field. While the work I did felt impactful, I felt like I lacked a sense of driving innovation, and so I decided to pursue a PhD at MIT.
My doctorate in Michael Strano’s lab has focused on a novel material at the intersection of polymers and nanomaterials. This material, called 2DPA-1, is like a combination of graphene, the strongest and most conductive material, with Kevlar, which is what makes up bulletproof vests. My thesis has been pivotal in establishing the characterization tools for this material so that future researchers can optimize its properties for different applications. Going forward, I’ve signed an offer letter with a startup that is making portable nuclear reactors for areas without stable grid electricity. I’ll work on various problems surrounding the materials that make up the reactors.
I always knew that I wanted my dog, Vinny, to have a doctoral gown for graduation. He’s been with me throughout my entire PhD and has been a pivotal member of my research group, helping everyone by being cute and reducing their stress. I couldn’t find any specific vendors online, and I love learning crafts to make custom items (crochet, knitting, and embroidery to make my own clothes; bookbinding to make my own journals and my physical thesis; and pottery to make my own mugs and dishes), so I thought: Why not try to sew a gown for him? I watched and read a few tutorials, used the sewing machines at Metropolis, and hand-sewed the finishing touches. I’m a bit of a perfectionist and could keep working on it, but I know that Vinny looks cute regardless of what he wears. I am so delighted and grateful that Vinny was part of my ceremony. He’s been such a pivotal part of my PhD journey, and my life as a whole. I can’t imagine a finer end to my time at MIT!”
—Michelle Quien PhD ’26, graduate of the Department of Chemical Engineering
Chilling Effects
Younger Americans have soured on the second Donald Trump presidency, but they are not protesting it.
Despite an unpopular Iran war and an even more unpopular Trump administration, college campus protests nationwide have gone silent. And at many schools, student activism is virtually nonexistent.
This silence comes in the wake of a relentless Trump administration war on campus speech that has involved lawsuits, arrests, deportations and expulsions.
Reports cite a range of complicated factors for the restraint, from apathy to technology-induced incapacity. But as ...
