A significant challenge for researchers in materials science and drug discovery is that even the most minor change to a molecule’s structure can completely alter its function. Historically, making these adjustments meant researchers had to re-synthesize the target molecule from scratch — a time-consuming and expensive bottleneck akin to tearing down a house just to move a lamp.

In an exciting discovery recently published in Nature, MIT chemists led by Professor Alison Wendlandt have developed a precision technique that allows scientists to seamlessly relocate alcohol functional groups from one spot on a molecule to a neighboring site. This process bypasses the need to rebuild the entire structure and is the result of a multi-year collaboration with Bristol Myers Squibb.

Functional group repositioning

Using a special light-sensitive molecule called decatungstate as a catalyst, the reaction triggers a highly controlled “migration” of the alcohol group. The process is remarkably predictable, ensuring the molecule retains its precise 3D shape and orientation throughout the move.

The ability to implement subtle structural tweaks without the waste of “from-scratch” synthesis eliminates a primary hurdle that has long plagued the field. Furthermore, because the reaction is gentle enough to work on complex, nearly finished structures, it serves as a powerful fine-tuning tool for late-stage drug candidates.

Precision editing to unlock new chemical designs

When combined with existing chemical methods, this tool provides new pathways to create challenging molecular architectures and oxygenation patterns that were previously out of reach.

“This alcohol migration strategy allows for precise, molecular-level tuning of oxygen atom positions,” says Qian Xu, the co-first author of the paper and a postdoc in the Wendlandt Group. “With predictable stereo- and regioselectivity and late-stage operability, it presents an enticing chance to modify natural products and drug molecules through ‘editing.’”

Ultimately, this precision editing tool holds the potential to dramatically improve the efficiency of molecular design campaigns, accelerating the development of new pharmaceuticals, materials, and agrochemicals.

In addition to Wendlandt and Xu, MIT contributors include co-lead author and graduate student Yichen Nie, recent postdoc Ronghua Zhang, and professor of chemistry Jeremiah A. Johnson. Other authors include Jacob-Jan Haaksma of the University of Groningen in The Netherlands; Natalie Holmberg-Douglas, Farid van der Mei, and Chloe Williams of of Bristol Myers Squibb; and Paul M. Scola of Actithera.

Cells rely on tiny molecules called microRNAs to tune which genes are active and when. Cells must carefully control the lifespan of microRNAs to prevent widespread disruption to gene regulation.

A new study led by researchers at MIT’s Whitehead Institute for Biomedical Research and Germany’s Max Planck Institute of Biochemistry reveals how cells selectively eliminate certain microRNAs through an unexpectedly intricate molecular recognition system. The open-access work, published on March 18 in Nature, shows that the process requires two separate RNA signals, similar to how many digital systems require two forms of identity verification before granting access.

The findings explain how cells use this “two-factor authentication” system to ensure that only intended microRNAs are destroyed, leaving the rest of the gene regulation machinery in operation.

MicroRNAs are short strands of RNA that help control gene expression. Working together with a protein called Argonaute, they bind to specific messenger RNAs — the molecules that carry genetic instructions from DNA to the cell’s protein-making machinery — and trigger their destruction. In this way, microRNAs can reduce the production of specific proteins.

While scientists recognized that microRNAs could be destroyed through a pathway known as target-directed microRNA degradation, or TDMD, the details of how cells recognized which microRNAs to eliminate remained unclear.

“We knew there was a pathway that could target microRNAs for degradation, but the biochemical mechanism behind it wasn’t understood,” says MIT Professor David Bartel, a Whitehead Institute member and co-senior author of the study.

Earlier work from Bartel’s lab and others had identified a key player in this pathway: the ZSWIM8 E3 ubiquitin ligase. E3 ubiquitin ligases are involved in the cell’s recycling system and attach a small molecular tag called ubiquitin to other proteins, marking them for destruction.

The researchers first showed that the ZSWIM8 E3 ligase specifically binds and tags Argonaute, the protein that holds microRNAs and helps regulate genes. The researchers’ next challenge was to understand how this machinery recognized only Argonaute complexes carrying specific microRNAs that should be degraded.

The answer turned out to be surprisingly sophisticated.

Using a combination of biochemistry and cryo-electron microscopy — an imaging technique that reveals molecular structures at near-atomic resolution — the researchers discovered that the degradation system relies on a dual-RNA recognition process. First, Argonaute must carry a specific microRNA. Second, another RNA molecule called a “trigger RNA” must bind to that microRNA in a particular way.

The degradation machinery activates only when both signals are present.

This dual requirement ensures exquisite specificity. Each cell contains over a hundred thousand Argonaute–microRNA complexes regulating many genes, and destroying them indiscriminately would disrupt essential biological processes.

“The vast majority of Argonaute molecules in the cell are doing useful work regulating gene expression,” says Bartel, who is a professor of biology at MIT and also a Howard Hughes Medical Institute investigator. “You only want to degrade the ones carrying a particular microRNA and bound to the right trigger RNA. Without that specificity, the cell would lose its microRNAs and the essential regulation that they provide.”

The structural images revealed complex molecular interactions. The ZSWIM8 ligase detects multiple structural changes that occur when the two RNAs bind together within the Argonaute protein.

“When we saw the structure, everything clicked,” says Elena Slobodyanyuk, a graduate student in Bartel’s lab and co-first author of the study. “You could see how the pairing of the trigger RNA with the microRNA reshapes the Argonaute complex in a way that the ligase can recognize.”

Beyond explaining how TDMD works, the findings may impact how scientists think about the regulation of RNA molecules more broadly.

“A lot of E3 ligases recognize their targets through simpler signals,” says Jakob Farnung, co-first author and researcher in the Department of Molecular Machines and Signaling at the Max Planck Institute of Biochemistry. “It was like opening a treasure chest where every detail revealed something new and mesmerizing.”

MicroRNAs typically persist in cells for much longer time periods than most messenger RNAs, but some degrade far more quickly, and the TDMD pathway appears to account for many of these unusually short-lived microRNAs.

The researchers are now investigating whether other RNAs can trigger similar degradation pathways and whether additional microRNAs are regulated through variations of the mechanism shown in this study.

“This opens up a whole new way of thinking about how RNA molecules can control protein degradation,” says Brenda Schulman, study co-senior author and director of the Department of Molecular Machines and Signaling at the Max Planck Institute of Biochemistry. “Here, the recognition was far more elaborate than expected. There’s likely much more left to discover.”

Uncovering the details of this intricate regulatory system required interdisciplinary collaboration, combining expertise in RNA biochemistry, structural biology, and ubiquitin enzymology to solve this long-standing molecular puzzle.

“This was a project that required the strengths of two labs working at the forefront of their fields,” says Schulman, who is also an alum of Whitehead Institute. “It was an incredible team effort.”

Chronic wound infections are notoriously difficult to manage because some bacteria can actively interfere with the body’s immune defenses. In wounds, Enterococcus faecalis (E. faecalis) is particularly resilient — it can survive inside tissues, alter the wound environment, and weaken immune signals at the injury site. This disruption creates conditions where other microbes can easily establish themselves, resulting in multi-species infections that are complex and slow to resolve. Such persistent wounds, including diabetic foot ulcers and post-surgical infections, place a heavy burden on patients and health care systems, and sometimes lead to serious complications such as amputations.

Now, researchers have discovered how E. faecalis releases lactic acid to acidify its surroundings and suppresses the immune-cell signal needed to start a proper response to infection. By silencing the body’s defenses, the bacterium can cause persistent and hard-to-treat wound infections. This explains why some wounds struggle to heal, even with treatment, and why infections involving multiple bacteria are especially difficult to eradicate.

The work was led by researchers from the Singapore-MIT Alliance for Research and Technology (SMART) Antimicrobial Resistance (AMR) interdisciplinary research group, alongside collaborators from the Singapore Centre for Environmental Life Sciences Engineering at Nanyang Technological University (NTU Singapore), MIT, and the University of Geneva in Switzerland.

In a paper titled “Enterococcus faecalis-derived lactic acid suppresses macrophage activation to facilitate persistent and polymicrobial wound infections,” recently published in Cell Host & Microbe, the researchers documented how E. faecalis releases large amounts of lactic acid during infection. This acidity suppresses the activation of macrophages — immune cells that normally help to clear infections — and interferes with several important internal processes that help the cell recognize and respond to infection. As a result, the mechanisms that cells rely on to send out “danger” signals are suppressed, leaving the macrophages unable to fully activate.

Researchers found that E. faecalis uses a two‑step mechanism to achieve this. Lactic acid enters the macrophages through a lactate transporter called MCT‑1 and also binds to a lactate-sensing receptor, GPR81, on the cell surface. By engaging both pathways, the bacterium effectively shuts down downstream immune signalling and blocks the macrophage’s inflammatory response, allowing E. faecalis to persist in the wound much longer than it should. Specifically, the lactic acid prevents a key immune alarm signal, known as NF-κB, from switching on inside these cells.

This was proven in a mouse wound model, where strains of E. faecalis that could not make lactic acid were cleared much more quickly, and the wounds also showed stronger immune activity. In wounds infected with both E. faecalis and Escherichia coli, the weakened immune response caused by lactic acid also allowed E. coli to grow better. This explains why wound infections often involve multiple species of bacteria and become harder to treat over time, particularly since E. faecalis is among the most common bacteria found in chronic wounds.

“Chronic wound infections often fail not because antibiotics are powerless, but because the immune system has effectively been ‘switched off’ at the infection site. We found that E. faecalis floods the wound with lactic acid, lowering pH and muting the NF‑κB alarm inside macrophages — the very cells that should be calling for help. By pinpointing how acidity rewires immune signalling, we now have clear targets to reactivate the immune response,” says first author Ronni da Silva, research scientist at SMART AMR, former postdoc in the lab of co-author and MIT professor of biology Jianzhu Chen, and SCELSE-NTU visiting researcher.

“This discovery strengthens our understanding of host-pathogen interactions and offers new directions for developing treatments and wound care that target the bacteria’s immunosuppressive strategies. By revealing how the immune response is shut down, this research may help improve infection management and support better recovery outcomes for patients, especially those with chronic wounds or weakened immunity,” says Kimberly Kline, principal investigator at SMART AMR, SCELSE-NTU visiting academic, professor at the University of Geneva, and corresponding author of the paper.

By identifying lactic‑acid‑driven immune suppression as a root cause of persistent wound infections, this work highlights the potential of treatment approaches that support the immune system, rather than rely on antibiotics alone. This could lead to therapies that help wounds heal more reliably and reduce the risk of complications. Potential directions include reducing acidity in the wound or blocking the signals that lactic acid uses to switch off immune cells.

Building on their study, the researchers plan to explore validation in additional pathogens and human wound samples, followed by assessments in advanced preclinical models ahead of any potential clinical trials.

The research was partially supported by the National Research Foundation Singapore under its Campus for Research Excellence and Technological Enterprise program.

"There's a lot at stake here," Rob Bonta says of the legal battle to restore EPA's endangerment finding, which underpins federal climate regs.

The Trump administration has removed references to climate change at several National Park Service sites.

The Trump administration extended industry's ability to flare gas during emergencies.

It's the latest move in a lawsuit against the administration's plans to shutter the National Center for Atmospheric Research.

The campaign from a Democratic-aligned group comes as gas prices top $4 a gallon.

A generation of workers that powered growth by digging coal from underground mines in Datong, a city known as China's coal capital, now seeks new livelihoods.

Beijing HyperStrong Technology's CEO said total deliveries are projected to reach 70 gigawatt-hours this year.

Bright, windy weather sparked a surge in renewable electricity supplies that overwhelmed demand over the weekend.

Storms and heavy rainfall began across Afghanistan about 12 days ago, affecting most of the country's 34 provinces.

According to a new law, the Hong Kong police can demand that you reveal the encryption keys protecting your computer, phone, hard drives, etc.—even if you are just transiting the airport.

In a security alert dated March 26, the U.S. Consulate General said that, on March 23, 2026, Hong Kong authorities changed the rules governing enforcement of the National Security Law. Under the revised framework, police can require individuals to provide passwords or other assistance to access personal electronic devices, including cellphones and laptops.

...

U.S. News and World Report has again placed MIT’s graduate program in engineering at the top of its annual rankings, released today. The Institute has held the No. 1 spot since 1990, when the magazine first ranked such programs.

The MIT Sloan School of Management also placed highly, occupying the No. 6 spot for the best graduate business programs.

Among individual engineering disciplines, MIT placed first in six areas: aerospace/aeronautical/astronautical engineering, chemical engineering, computer engineering (tied with the University of California at Berkeley), electrical/electronic/communications engineering (tied with Stanford University and Berkeley), materials engineering, and mechanical engineering. It placed second in nuclear engineering.

In the rankings of individual MBA specialties, MIT placed first in four areas: business analytics, entrepreneurship (with Stanford), production/operations, and supply chain/logistics. It placed second in executive MBA programs (with the University of Chicago).

U.S. News bases its rankings of graduate schools of engineering and business on two types of data: reputational surveys of deans and other academic officials, and statistical indicators that measure the quality of a school’s faculty, research, and students. The magazine’s less-frequent rankings of graduate programs in the sciences, social sciences, and humanities are based solely on reputational surveys.

In the sciences, ranked by U.S. News for the first time in four years, MIT’s doctoral programs placed first in four areas: biology (with Scripps Research Institute), chemistry (with Berkeley and Caltech), computer science (with Carnegie Mellon University and Stanford), and physics (with Caltech, Princeton University, and Stanford). The Institute placed second in mathematics (with Harvard University, Stanford, and Berkeley).

To improve data center efficiency, multiple storage devices are often pooled together over a network so many applications can share them. But even with pooling, significant device capacity remains underutilized due to performance variability across the devices.

MIT researchers have now developed a system that boosts the performance of storage devices by handling three major sources of variability simultaneously. Their approach delivers significant speed improvements over traditional methods that tackle only one source of variability at a time.

The system uses a two-tier architecture, with a central controller that makes big-picture decisions about which tasks each storage device performs, and local controllers for each machine that rapidly reroute data if that device is struggling.

The method, which can adapt in real-time to shifting workloads, does not require specialized hardware. When the researchers tested this system on realistic tasks like AI model training and image compression, it nearly doubled the performance delivered by traditional approaches. By intelligently balancing the workloads of multiple storage devices, the system can increase overall data center efficiency.

“There is a tendency to want to throw more resources at a problem to solve it, but that is not sustainable in many ways. We want to be able to maximize the longevity of these very expensive and carbon-intensive resources,” says Gohar Chaudhry, an electrical engineering and computer science (EECS) graduate student and lead author of a paper on this technique. “With our adaptive software solution, you can still squeeze a lot of performance out of your existing devices before you need to throw them away and buy new ones.”

Chaudhry is joined on the paper by Ankit Bhardwaj, an assistant professor at Tufts University; Zhenyuan Ruan PhD ’24; and senior author Adam Belay, an associate professor of EECS and a member of the MIT Computer Science and Artificial Intelligence Laboratory. The research will be presented at the USENIX Symposium on Networked Systems Design and Implementation.

Leveraging untapped performance

Solid-state drives (SSDs) are high-performance digital storage devices that allow applications to read and write data. For instance, an SSD can store vast datasets and rapidly send data to a processor for machine-learning model training.   

Pooling multiple SSDs together so many applications can share them improves efficiency, since not every application needs to use the entire capacity of an SSD at a given time. But not all SSDs perform equally, and the slowest device can limit the overall performance of the pool.

These inefficiencies arise from variability in SSD hardware and the tasks they perform.

To utilize this untapped SSD performance, the researchers developed Sandook, a software-based system that tackles three major forms of performance-hampering variability simultaneously. “Sandook” is an Urdu word that means “box,” to signify “storage.”

One type of variability is caused by differences in the age, amount of wear, and capacity of SSDs that may have been purchased at different times from multiple vendors.

The second type of variability is due to the mismatch between read and write operations occurring on the same SSD. To write new data to the device, the SSD must erase some existing data. This process can slow down data reads, or retrievals, happening at the same time.

The third source of variability is garbage collection, a process of gathering and removing outdated data to free up space. This process, which slows SSD operations, is triggered at random intervals that a data center operator cannot control.

“I can’t assume all SSDs will behave identically through my entire deployment cycle. Even if I give them all the same workload, some of them will be stragglers, which hurts the net throughput I can achieve,” Chaudhry explains.

Plan globally, react locally

To handle all three sources of variability, Sandook utilizes a two-tier structure. A global schedular optimizes the distribution of tasks for the overall pool, while faster schedulers on each SSD react to urgent events and shift operations away from congested devices.

The system overcomes delays from read-write interference by rotating which SSDs an application can use for reads and writes. This reduces the chance reads and writes happen simultaneously on the same machine.

Sandook also profiles the typical performance of each SSD. It uses this information to detect when garbage collection is likely slowing operations down. Once detected, Sandook reduces the workload on that SSD by diverting some tasks until garbage collection is finished.

“If that SSD is doing garbage collection and can’t handle the same workload anymore, I want to give it a smaller workload and slowly ramp things back up. We want to find the sweet spot where it is still doing some work, and tap into that performance,” Chaudhry says.

The SSD profiles also allow Sandook’s global controller to assign workloads in a weighted fashion that considers the characteristics and capacity of each device.

Because the global controller sees the overall picture and the local controllers react on the fly, Sandook can simultaneously manage forms of variability that happen over different time scales. For instance, delays from garbage collection occur suddenly, while latency caused by wear and tear builds up over many months.

The researchers tested Sandook on a pool of 10 SSDs and evaluated the system on four tasks: running a database, training a machine-learning model, compressing images, and storing user data. Sandook boosted the throughput of each application between 12 and 94 percent when compared to static methods, and improved the overall utilization of SSD capacity by 23 percent.

The system enabled SSDs to achieve 95 percent of their theoretical maximum performance, without the need for specialized hardware or application-specific updates.

“Our dynamic solution can unlock more performance for all the SSDs and really push them to the limit. Every bit of capacity you can save really counts at this scale,” Chaudhry says.

In the future, the researchers want to incorporate new protocols available on the latest SSDs that give operators more control over data placement. They also want to leverage the predictability in AI workloads to increase the efficiency of SSD operations.

“Flash storage is a powerful technology that underpins modern datacenter applications, but sharing this resource across workloads with widely varying performance demands remains an outstanding challenge. This work moves the needle meaningfully forward with an elegant and practical solution ready for deployment, bringing flash storage closer to its full potential in production clouds,” says Josh Fried, a software engineer at Google and incoming assistant professor at the University of Pennsylvania, who was not involved with this work.

This research was funded, in part, by the National Science Foundation, the U.S. Defense Advanced Research Projects Agency, and the Semiconductor Research Corporation.

Nature Climate Change, Published online: 07 April 2026; doi:10.1038/s41558-026-02611-2

Lessons from the International Court of Justice Advisory Opinion for Indigenous rights

Nature Climate Change, Published online: 07 April 2026; doi:10.1038/s41558-026-02602-3

Meeting global temperature targets requires deep mitigation across sectors. Moving away from cost optimality when allocating mitigation by sector, the authors link integrated assessment models and portfolio analysis to identify and balance trade-offs between Sustainable Development Goal indicators.

Mike Masnick points out that the recent New Mexico court ruling against Meta has some bad implications for end-to-end encryption, and security in general:

If the “design choices create liability” framework seems worrying in the abstract, the New Mexico case provides a concrete example of where it leads in practice.

One of the key pieces of evidence the New Mexico attorney general used against Meta was the company’s 2023 decision to add end-to-end encryption to Facebook Messenger. The argument went like this: predators used Messenger to groom minors and exchange child sexual abuse material. By encrypting those messages, Meta made it harder for law enforcement to access evidence of those crimes. Therefore, the encryption was a design choice that enabled harm...

Google says that it will fully transition to post-quantum cryptography by 2029. I think this is a good move, not because I think we will have a useful quantum computer anywhere near that year, but because crypto-agility is always a good thing.

Slashdot thread.

Administrator Lee Zeldin says his agency can't regulate greenhouse gases without congressional approval. Some legal experts disagree.