Science says we’ve been nurturing “gifted” kids all wrong

Exceptional performers play a major role in driving innovation and tackling some of the world’s most urgent challenges. Because of this, societies have a strong stake in understanding how top-level talent develops. A new review published in the journal Science argues that many long standing approaches to gifted education and talent development rest on flawed assumptions. For the first time, an international and interdisciplinary research team has brought together evidence on how world-class performers emerge in science, classical music, chess, and sports.

For decades, research on giftedness and expertise has followed a familiar model. Outstanding achievement was thought to depend on strong early performance, such as excelling in school subjects, sports, or concerts, combined with specific abilities like intelligence, physical coordination, or musical talent. These traits were believed to need years of intense, discipline-focused training to produce elite results. As a result, many talent programs concentrate on identifying the top young performers early and pushing them to specialize quickly.

According to new findings led by Arne Güllich, professor of sports science at RPTU University Kaiserslautern-Landau, this approach may not be the most effective way to nurture future high achievers.

Why Earlier Research Missed the Full Picture

Until recently, most studies of giftedness focused on young or sub-elite performers. These groups included school and college students, youth athletes, young chess players, and musicians training at conservatories. However, evidence drawn from adult world-class athletes has begun to challenge conclusions based on these earlier samples.

“Traditional research into giftedness and expertise did not sufficiently consider the question of how world-class performers at peak performance age developed in their early years,” Arne Güllich explains. The goal of the new Review was to address this gap by examining how elite performers actually progressed over time.

To do this, Güllich worked with an international research team that included Michael Barth, assistant professor of sports economics at the University of Innsbruck, D. Zach Hambrick, professor of psychology at Michigan State University, and Brooke N. Macnamara, professor of psychology at Purdue University. Their findings are now published in Science.

Pooling Evidence Across Fields

The researchers reexamined large datasets from many previous studies, analyzing the developmental histories of 34,839 top-level performers from around the world. The group included Nobel Prize winners in the sciences, Olympic medalists, elite chess players, and leading classical music composers. This effort made it possible, for the first time, to compare how world-class performers develop across very different disciplines.

Early Stars Are Rarely Future Legends

One of the most striking conclusions is that elite performers follow a developmental path that differs from long-held assumptions. “And a common pattern emerges across the different disciplines,” Güllich notes.

First, individuals who stand out as the best at a young age are usually not the same people who become the best later in life. Second, those who eventually reached the highest levels tended to improve gradually during their early years and were not top performers within their age group. Third, future world-class achievers typically did not focus on a single discipline early on. Instead, they explored a range of activities, such as different academic subjects, musical genres, sports, or professions (e.g., different subjects of study, genres of music, sports, or professions).

How Variety Builds Stronger Performers

The researchers propose three ideas that may help explain these patterns. “We propose three explanatory hypotheses for discussion,” says Güllich.

The search-and-match hypothesis suggests that exposure to multiple disciplines increases the likelihood of eventually finding the best personal fit. The enhanced-learning-capital hypothesis proposes that learning in diverse areas strengthens overall learning capacity, making it easier to continue improving later at the highest level within a chosen field. The limited-risks hypothesis argues that engaging in multiple disciplines reduces the chance of setbacks such as burnout, unhealthy work-rest imbalances, loss of motivation, or physical injury in psychomotor disciplines (sports, music).

Arne Güllich summarizes the combined effect of these factors: “Those who find an optimal discipline for themselves, develop enhanced potential for long-term learning, and have reduced risks of career-hampering factors, have improved chances of developing world-class performance.”

Encouraging Breadth Instead of Early Specialization

Based on these findings, Güllich offers clear guidance on how young talent should be supported. The evidence suggests avoiding early specialization in a single field. Instead, young people should be encouraged and given opportunities to explore several areas of interest and receive support in two or three disciplines.

These areas do not need to be closely related. Combinations like language and mathematics, or geography and philosophy, can be equally valuable. Albert Einstein provides a famous example — one of the most important physicists, who was also deeply engaged with music and played the violin from an early age.

Implications for Policy and Practice

The authors argue that these insights should inform changes in how talent development programs are designed. Policymakers and program leaders can move toward approaches grounded in evidence rather than tradition.

As Güllich concludes, “This may enhance opportunities for the development of world-class performers — in science, sports, music, and other fields.”

Share Button

Ancient sewers expose a hidden health crisis in Roman Britain

Scientists studying ancient sewer drains at the Roman fort of Vindolanda, located near Hadrian’s Wall, have uncovered evidence that the people living there were infected with three different intestinal parasites: roundworm, whipworm, and Giardia duodenalis.

All three parasites spread through poor sanitation, typically when food, water, or hands are contaminated with human feces. Roundworms can grow to 20-30cm in length, while whipworms reach about 5cm. Giardia duodenalis is a microscopic protozoan parasite known for causing outbreaks of severe diarrhea. The discovery marks the first confirmed evidence of Giardia duodenalis in Roman Britain.

Vindolanda and the Roman Frontier in Britain

Vindolanda sat close to Hadrian’s Wall in northern England. The wall was constructed by the Romans in the early 2nd century AD to protect the province of ‘Britannia’ from northern tribes and remained in use until the late 4th century. The fort itself lies between Carlisle and Corbridge in what is now Northumberland, Britain.

Stretching east to west from the North Sea to the Irish Sea, Hadrian’s Wall featured a series of forts and towers placed at regular intervals. It was defended by a mix of infantry, archers, and cavalry drawn from across the Roman Empire.

A Site Known for Remarkable Preservation

Vindolanda is well known among archaeologists for its exceptional preservation of organic materials, thanks to the site’s waterlogged soil. Discoveries include more than 1,000 thin wooden writing tablets that provide rare insight into everyday life at the fort, along with over 5,000 Roman leather shoes.

How Researchers Studied the Ancient Sewers

The parasite analysis focused on sediment taken from a sewer drain connected to the latrine block of a bath complex dating to the 3rd century CE. The research was carried out jointly by scientists from the universities of Cambridge and Oxford and published in the journal Parasitology.

Researchers collected 50 sediment samples from along the drain, which stretched roughly nine meters and carried waste from a communal latrine into a stream north of the fort. Along with the sediment, archaeologists recovered artifacts such as Roman beads, pottery fragments, and animal bones.

The samples were divided between laboratories at Cambridge and Oxford, where scientists examined them under microscopes to search for ancient helminth eggs, which are produced by parasitic worms that infect humans and animals.

Evidence of Worms and Giardia Infection

About 28% of the samples contained eggs from either roundworm or whipworm. One sample showed traces of both parasites. That same sample was further tested using a bio-molecular method called ‘ELISA’, a technique in which antibodies bind to proteins produced by single-celled organisms. This analysis revealed the presence of Giardia duodenalis.

The research team also examined a sample linked to an earlier fort from the 1st century CE. That fort was built around 85 CE and abandoned by 91/92 CE. The sediment came from a defensive ditch and also contained roundworm and whipworm eggs.

How Parasites Affected Roman Soldiers

“The three types of parasites we found could have led to malnutrition and cause diarrhea in some of the Roman soldiers,” said Dr. Marissa Ledger, who led the Cambridge portion of the research as part of her PhD at the University of Cambridge’s Department of Archaeology.

“While the Romans were aware of intestinal worms, there was little their doctors could do to clear infection by these parasites or help those experiencing diarrhea, meaning symptoms could persist and worsen. These chronic infections likely weakened soldiers, reducing fitness for duty. Helminths alone can cause nausea, cramping and diarrhea.”

Study senior author Dr. Piers Mitchell, an Affiliated Scholar at Cambridge’s McDonald Institute for Archaeological Research, explained that Giardia outbreaks could have been especially dangerous. “Some soldiers could have become severely ill from dehydration during summer outbreaks of Giardia, which are often linked to contaminated water and can infection dozens of people at a time. Untreated giardiasis can drag on for weeks, causing dramatic fatigue and weight loss.”

Mitchell added that “The presence of the fecal-oral parasites we found suggests conditions were ripe for other intestinal pathogens such as Salmonella and Shigella, which could have triggered additional disease outbreaks.”

How Vindolanda Compares to Other Roman Sites

According to the researchers, the dominance of fecal-oral parasites at Vindolanda mirrors findings from other Roman military sites, including Carnuntum in Austria, Valkenburg on Rhine in the Netherlands, and Bearsden in Scotland. In contrast, large urban centers like London and York show a wider range of parasites, including fish and meat tapeworms.

“Despite the fact that Vindolanda had communal latrines and a sewer system, this still did not protect the soldiers from infecting each other with these parasites,” said Dr. Patrik Flammer, who analyzed samples at the University of Oxford.

What Ancient Parasites Reveal About the Past

“The study of ancient parasites helps us to know the pathogens that infected our ancestors, how they varied with lifestyle, and how they changed over time,” said Prof Adrian Smith, who led the Oxford laboratory involved in the research.

Dr. Andrew Birley, CEO of the Vindolanda Charitable Trust and leader of ongoing excavations at the site, said the findings add to a growing picture of life on Rome’s northern frontier. “Excavations at Vindolanda continue to find new evidence that helps us to understand the incredible hardships faced by those posted to this northwestern frontier of the Roman Empire nearly 2,000 years ago, challenging our preconceptions about what life was really like in a Roman frontier fort and town.”

W. H. Auden once wrote of a miserable Roman soldier guarding a cold, rain-soaked wall in northern Europe, mentioning “lice in my tunic and a cold in my nose.” Based on this new evidence, chronic stomach trouble could easily be added to that list.

Share Button

Weight-loss jabs: What happens when you stop?

You may have lost the weight you wanted to lose – but now you’ve stopped the jabs, how easy is it to keep it off?

Share Button

This “mushroom” is not a fungus, it’s a bizarre plant that breaks all the rules

In the damp shade beneath moss-covered trees, high in the mountains of Taiwan and mainland Japan or deep within the subtropical forests of Okinawa, an unusual organism quietly grows. At first glance, it resembles a mushroom. In reality, it is a plant called Balanophora, and it possesses some of the smallest flowers and seeds known in the plant world.

Unlike most plants, Balanophora contains no chlorophyll and cannot perform photosynthesis. It also lacks a conventional root system to draw water from the soil. Instead, it survives entirely by attaching itself to the roots of specific nearby trees and stealing the nutrients it needs. Some species and populations take this strangeness even further by producing seeds without fertilization — a reproductive strategy that is extremely rare among plants.

Scientists uncover the secrets of a long-mysterious plant

The genus Balanophora takes its name from its acorn-like appearance (Greek: balanos, acorn; phoros, bearing), and it has puzzled scientists for generations. Because the plant is rare and restricted to highly specific habitats that are increasingly threatened by human activity, most research has been limited to isolated populations.

That is now changing. A collaborative team from the Okinawa Institute of Science and Technology (OIST), Kobe University, and the University of Taipei has conducted a broad survey of Balanophora across its scattered and hard-to-reach habitats. Their findings, published in New Phytologist, trace the plant’s evolutionary history, reveal how its internal structures have adapted to a parasitic lifestyle, and open new doors for future research into this unusual lineage.

As study lead author Dr. Petra Svetlikova, Science and Technology Associate at OIST, explains: “Balanophora has lost much of what defines it as a plant, but retained enough to function as a parasite. It’s a fascinating example of how something so strange can evolve from an ancestor that looked like a normal plant with leaves and a normal root system.”

Shrinking plastids and life without photosynthesis

Parasitic plants often undergo dramatic internal changes as they become more dependent on their hosts. One common trend is the reduction or loss of plastids — a category of plant organelles that includes chloroplasts, which enable photosynthesis in most plants.

Even though Balanophora relies completely on its host trees for nutrition, the researchers found that it has not eliminated its plastids. Instead, these structures have been pared down to a minimal form. While non-parasitic plants may use up to 200 genes to build and maintain plastids, Balanophora retains only about 20. Despite this extreme reduction, more than 700 proteins are still transported into these plastids from the surrounding cell, indicating that they continue to perform essential functions.

Professor Filip Husnik, head of the Evolution, Cell Biology, and Symbiosis Unit at OIST, notes the surprise of this discovery. “That Balanophora plastids are still involved in the biosynthesis of many compounds unrelated to photosynthesis was surprising. It implies that the order and timing of plastid reduction in non-photosynthetic plants is similar to other eukaryotes, such as the malaria-causing parasite, Plasmodium, which originated from a photosynthetic ancestor.”

An ancient lineage shaped by islands

By examining samples from many different populations, the team reconstructed the evolutionary tree of Balanophora and traced how it spread across subtropical regions of East Asia. The plant belongs to the family Balanophoraceae, one of the oldest known groups of fully parasitic plants.

This family began diversifying during the mid-Cretaceous period, roughly 100 million years ago — making it one of the earliest land plant lineages to abandon photosynthesis entirely.

Reproduction without sex and the risks of survival

Balanophora‘s reproductive strategies are just as unusual as its appearance and lifestyle. Reproductive methods vary widely between species and even between populations. Some require fertilization to produce seeds, while others can also reproduce without fertilization, a process known as facultative agamospermy. In the most extreme cases, some species are obligately agamospermous, meaning they never reproduce sexually at all.

“Obligate agamospermy is exceedingly rare in the plant kingdom, because it typically carries a lot of negative downsides — lack of genetic diversity, accumulation of bad mutations, dependence on specific conditions, higher extinction risk, and so on,” says Dr. Svetlikova. “Fascinatingly, we found that the obligately agamospermous Balanophora species were all island species — and we speculate that more Balanophora species may be facultative, or even obligate, agamosperms.”

One advantage of this reproductive approach is that a single female plant can establish a new population after reaching an island. This ability allows Balanophora to spread quickly into the narrow ecological niche it prefers: dark, moist forest undergrowth where few other plants can survive.

A fragile future for a highly specialized plant

Despite its ability to clone itself, Balanophora is extremely selective about its hosts. Each population typically parasitizes only a small number of tree species. This specialization makes the plant especially vulnerable to environmental change.

Dr. Svetlikova emphasizes the importance of collaboration and conservation. “We’re very thankful to our collaborators Dr. Huei-Jiun Su and Dr. Kenji Suetsugu, experts on parasitic plants, for their help in sampling the studied Balanophora species, and to local authorities in Okinawa that allowed us to study these extraordinary plants,” she says. “Most known habitats of Balanophora are protected in Okinawa, but the populations face extinction by logging and unauthorized collection. We hope to learn as much as we can about this fantastic, ancient plant before it’s too late. It serves as a reminder of how evolution continues to surprise us.”

Share Button

What scientists found inside Titan was not what anyone expected

A new examination of spacecraft data collected more than ten years ago suggests that Saturn’s largest moon, Titan, probably does not contain a massive ocean beneath its frozen surface, as scientists once believed. Instead, moving downward through Titan’s icy shell would likely reveal additional layers of ice that gradually transition into slushy pathways and isolated pockets of liquid water closer to the moon’s rocky interior.

Earlier interpretations of data from NASA’s Cassini mission to Saturn led scientists to propose a deep ocean of liquid water hidden beneath Titan’s ice. When researchers tested that idea using computer models, however, the results did not align with the physical characteristics seen in the data. A closer reanalysis produced new — slushier — conclusions. These results may prompt scientists to revisit assumptions about other icy worlds and refine how they search for life on Titan.

“Instead of an open ocean like we have here on Earth, we’re probably looking at something more like Arctic sea ice or aquifers, which has implications for what type of life we might find, but also the availability of nutrients, energy and so on,” said Baptiste Journaux, a University of Washington assistant professor of Earth and space sciences.

The study, published Dec. 17 in Nature, was led by NASA, with contributions from Journaux and Ula Jones, a UW graduate student of Earth and space sciences in his lab.

Cassini’s Legacy and Titan’s Unusual Surface

The Cassini mission began in 1997 and continued for nearly two decades, gathering extensive information about Saturn and its 274 moons. Titan — shrouded by a hazy atmosphere — stands out as the only place besides Earth where liquid is known to exist on the surface. With temperatures near -297 degrees Fahrenheit, that liquid is methane, not water. Methane forms lakes on Titan and even falls from the sky as rain.

As Titan travels around Saturn in an elongated orbit, scientists noticed that the moon stretches and compresses depending on its position relative to the planet. In 2008, researchers argued that this pronounced flexing could only occur if a large ocean existed beneath Titan’s crust.

“The degree of deformation depends on Titan’s interior structure. A deep ocean would permit the crust to flex more under Saturn’s gravitational pull, but if Titan were entirely frozen, it wouldn’t deform as much,” Journaux said. “The deformation we detected during the initial analysis of the Cassini mission data could have been compatible with a global ocean, but now we know that isn’t the full story.”

A Subtle Time Lag Reveals a Slushy Interior

The new research adds an important factor that earlier studies did not fully consider: timing. Titan’s changes in shape lag roughly 15 hours behind the strongest pull from Saturn’s gravity. Moving a thick, sticky material requires more energy than shifting a free flowing liquid, similar to how stirring honey takes more effort than stirring water. By measuring this delay, scientists could estimate how much energy Titan absorbs as it deforms, offering insight into how thick or viscous its interior must be.

The amount of energy lost, or dissipated, inside Titan turned out to be far greater than expected if a global liquid ocean were present.

“Nobody was expecting very strong energy dissipation inside Titan. That was the smoking gun indicating that Titan’s interior is different from what was inferred from previous analyses,” said Flavio Petricca, a postdoctoral fellow at NASA’s Jet Propulsion Laboratory and lead author of the study.

Based on these findings, the researchers propose an interior made up largely of slush, with significantly less liquid water than previously assumed. This slushy material is thick enough to explain the delayed response to Saturn’s gravity, while still containing enough water to allow Titan to change shape.

Radio Signals and Extreme Physics Support the Model

Petricca reached these conclusions by analyzing the frequencies of radio waves transmitted from the Cassini spacecraft during close fly-bys of Titan. Journaux helped interpret the results using thermodynamics. His work focuses on how water and minerals behave under intense pressure, knowledge that is critical for understanding whether other planetary environments might support life.

“The watery layer on Titan is so thick, the pressure is so immense, that the physics of water changes. Water and ice behave in a different way than sea water here on Earth,” Journaux said.

At his planetary cryo-mineral physics laboratory at UW, researchers have spent years developing methods to recreate the extreme conditions found on other worlds. Using this work, Journaux provided Petricca and his colleagues with data describing how water and ice are expected to behave deep inside Titan.

“We could help them determine what gravitational signal they should expect to see based on the experiments made here at UW,” Journaux said. “It was very rewarding.”

What Slush Could Mean for Life on Titan

“The discovery of a slushy layer on Titan also has exciting implications for the search for life beyond our solar system,” Jones said. “It expands the range of environments we might consider habitable.”

While the idea of a vast ocean once fueled optimism about life on Titan, the researchers suggest the updated picture may actually improve the odds. Their analysis indicates that Titan’s freshwater pockets could reach temperatures as high as 68 degrees Fahrenheit. In these smaller volumes of water, nutrients would be more concentrated than in a large ocean, potentially making it easier for simple life forms to survive.

Although scientists do not expect to find fish swimming through Titan’s slushy channels, any life discovered there might resemble organisms found in Earth’s polar regions.

Journaux is also part of NASA’s upcoming Dragonfly mission to Titan, which is scheduled to launch in 2028. The findings from this study will help inform that mission, and Journaux hopes future data will provide both evidence of life and a definitive answer about the presence of an ocean beneath Titan’s ice.

Co-authors include Steven D. Vance, Marzia Parisi, Dustin Buccino, Gael Cascioli, Julie Castillo-Rogez, Mark Panning and Jonathan I. Lunine from NASA; Brynna G. Downey at Southwest Research Institute; Francis Nimmo and Gabriel Tobie from the University of Nantes; Andrea Magnanini from the University of Bologna; Amirhossein Bagheri from the California Institute of Technology and Antonio Genova from Sapienza University of Rome.

This research was funded by NASA, the Swiss National Science Foundation and the Italian Space Agency.

Share Button

Deaths of despair were rising long before opioids

A new study suggests that falling participation in organized religion among middle-aged white Americans with lower levels of education may have contributed to the rise in so-called “deaths of despair.” These deaths include fatalities linked to drug overdoses, suicide, and alcoholic liver disease.

The researchers found a clear pattern at the state level. States that experienced the sharpest drops in church attendance between 1985 and 2000 also saw the largest increases in deaths from these causes during the same period.

A Trend That Began Before the Opioid Crisis

Deaths of despair are often associated with the arrival of OxyContin and other powerful opioids in the late 1990s. However, the new analysis indicates that the upward trend started earlier, at the same time religious participation began to decline.

“What we see in this study is the beginning of the story, before opioids became a major issue, and it shows rises in deaths of despair were already beginning to happen when the opioid crisis hit,” said Tamar Oostrom, co-author of the study and an assistant professor of economics at The Ohio State University.

Oostrom worked on the research with Tyler Giles of Wellsley College and Daniel Hungerman of the University of Notre Dame. The study was published online in the Journal of the European Economic Association.

Data Sources and Affected Populations

The research team combined survey data on religious involvement from the General Social Surveys with mortality records from the Centers for Disease Control and Prevention.

Their findings showed that the decline in religious participation was concentrated among white, middle-aged adults without a college degree. This was the same group that experienced the most pronounced increases in deaths of despair, Oostrom said.

The relationship between lower church attendance and higher mortality appeared consistently across genders and was seen in both rural and urban areas of the United States.

Blue Laws and Changes in Church Attendance

To strengthen their findings, the researchers examined the repeal of “blue laws,” which had previously restricted many businesses from operating on Sundays. These laws limited competition with church attendance by reducing alternative activities.

A major wave of repeals took place in 1985, when Minnesota, South Carolina, and Texas eliminated their blue laws. The researchers compared outcomes in those states with others that did not make similar changes at that time.

The analysis showed that repealing blue laws led to a 5- to 10-percentage-point drop in weekly attendance at religious services. In later years, those same states also experienced higher rates of deaths of despair.

Mortality Trends Before and After Opioids

Oostrom noted that deaths of despair among middle-aged white Americans had been steadily declining from the late 1970s through the early 1990s. That decline eventually stalled, a shift that aligns with both falling church attendance and the repeal of blue laws.

After OxyContin was introduced in 1996, mortality rates rose sharply.

“OxyContin and the opioid crisis made a bad situation worse, but the deaths of despair were already on the rise,” Oostrom said.

Why Churchgoing May Matter for Health

The study raises an important question: how could lower church attendance contribute to higher death rates?

Oostrom explained that people who stop attending religious services often lose social ties, which past research has shown play a crucial role in physical and mental health. However, the findings suggest that social connection alone does not fully explain the pattern.

The researchers did not observe similar declines in other types of social activities during the same period when church attendance was falling.

“Religion may provide some way of making sense of the world, some sense of identity in relation to others, that can’t easily be replaced by other forms of socialization,” Oostrom said.

She also emphasized that belief itself did not fade during the years studied.

“What changed is whether people identified as religious and whether they go to church. Those are the things that matter when it comes to deaths of despair,” she said.

Can Community Participation Reverse the Trend?

The findings raise the possibility that renewed involvement in religious organizations or even secular community groups might help counter rising mortality rates. However, the authors caution that existing evidence does not offer much optimism.

“To our knowledge, findings on this point have so far been pessimistic,” the researchers wrote.

Oostrom added that there is no clear sign that broader declines in community participation are reversing. She also noted that the positive effects of religious involvement on life satisfaction are difficult to reproduce through other forms of social engagement.

The growing role of social media in the 21st century may further reduce the likelihood of a meaningful reversal, she said.

“People are less religious now, and there hasn’t been a substitute that provides what religion provided to many people. And our paper suggests this could have long-term impacts on health and mortality,” Oostrom said.

Share Button

‘I thought I had flu but was told I had cancer’

Sophie Claxton, from Burnley, was 16 when she was diagnosed with acute lymphoblastic leukaemia.

Share Button

What’s really going on with flu this winter?

We’ve been told we’re facing an unprecedented superflu. Is it?

Share Button

Resident doctors in Scotland to go on strike for first time

Their union BMA Scotland has accused the government of reneging on a commitment to restore pay to 2008 levels.

Share Button

The 98% mystery: Scientists just cracked the code on “junk DNA” linked to Alzheimer’s

When people picture DNA, they often imagine a set of genes that shape our physical traits, influence behavior, and help keep our cells and organs functioning.

But genes make up only a small slice of our genetic code. Just around 2% of DNA contains our 20,000-odd genes. The other 98% has long been labelled the non-coding genome, or so-called ‘junk’ DNA. This larger portion includes many of the control switches that determine when genes turn on and how strongly they act.

Astrocytes and hidden DNA switches in the brain

Researchers from UNSW Sydney have now pinpointed DNA switches that help regulate astrocytes. Astrocytes are brain cells that support neurons, and they are known to be involved in Alzheimer’s disease.

In research published on December 18 in Nature Neuroscience, a team from UNSW’s School of Biotechnology & Biomolecular Sciences reported that they tested nearly 1000 possible switches in lab-grown human astrocytes. These switches are strings of DNA called enhancers. Enhancers can sit far from the genes they influence, sometimes separated by hundreds of thousands of DNA letters, which makes them difficult to investigate.

Testing nearly 1000 enhancers at once

To tackle that problem, the researchers combined CRISPRi with single-cell RNA sequencing. CRISPRi is a method that can switch off small stretches of DNA without cutting it. Single-cell RNA sequencing measures gene activity in individual cells. Together, the tools let the team examine the effects of nearly 1000 enhancers in a single large-scale test.

“We used CRISPRi to turn off potential enhancers in the astrocytes to see whether it changed gene expression,” says lead author Dr. Nicole Green.

“And if it did, then we knew we’d found a functional enhancer and could then figure out which gene — or genes — it controls. That’s what happened for about 150 of the potential enhancers we tested. And strikingly, a large fraction of these functional enhancers controlled genes implicated in Alzheimer’s disease.”

Cutting the list from 1000 candidates to about 150 confirmed switches greatly reduces the search area in the non-coding genome for genetic clues linked to Alzheimer’s disease.

“These findings suggest that similar studies in other brain cell types are needed to highlight the functional enhancers in the vast space of non-coding DNA”

Why “in-between” DNA matters for many diseases

Professor Irina Voineagu, who oversaw the study, says the results also provide a useful reference for interpreting other genetic research. The team’s findings create a catalogue of DNA regions that can help explain results from studies looking for disease-related genetic changes.

“When researchers look for genetic changes that explain diseases like hypertension, diabetes and also psychiatric and neurodegenerative disorders like Alzheimer’s disease — we often end up with changes not within genes so much, but in-between,” she says.

Her team directly tested those “in-between” stretches in human astrocytes and showed which enhancers truly control key brain genes.

“We’re not talking about therapies yet. But you can’t develop them unless you first understand the wiring diagram. That’s what this gives us — a deeper view into the circuitry of gene control in astrocytes.”

From gene switches to AI prediction models

Running nearly a thousand enhancer tests in the lab took painstaking effort. The researchers say this is the first time a CRISPRi enhancer screen of this size has been carried out in brain cells. Now that the groundwork has been done, the dataset can also be used to train computer models to predict which suspected enhancers are real gene switches, potentially saving years of lab work.

“This dataset can help computational biologists test how good their prediction models are at predicting enhancer function,” says Prof. Voineagu.

She adds that Google’s DeepMind team is already using the dataset to benchmark their recent deep learning model called AlphaGenome.

Potential tools for gene therapy and precision medicine

Because many enhancers are active only in specific cell types, targeting them could offer a way to fine-tune gene expression in astrocytes without changing neurons or other brain cells.

“While this is not close to being used in the clinic yet — and much work remains before these findings could lead to treatments — there is a clear precedent,” Prof. Voineagu says.

“The first gene editing drug approved for a blood disease — sickle cell anemia — targets a cell-type specific enhancer.”

Dr. Green says enhancer research could become an important part of precision medicine.

“This is something we want to look at more deeply: finding out which enhancers we can use to turn genes on or off in a single brain cell type, and in a very controlled way,” she says.

Share Button