. Scientific Frontline

Tuesday, March 12, 2024

Scientists develop a rapid gene-editing screen to find effects of cancer mutations

Using a variant of CRISPR genome-editing known as prime editing, MIT researchers have developed a method to screen cancer-associated genetic mutations much more easily and quickly than any existing approach. This illustration, by Samuel Gould’s brother Owen Gould, is an artistic interpretation of the research and the idea of “rewriting the genome,” explains Samuel.
Illustration Credit: Owen Gould
(CC BY-NC-ND 4.0 DEED)

Tumors can carry mutations in hundreds of different genes, and each of those genes may be mutated in different ways — some mutations simply replace one DNA nucleotide with another, while others insert or delete larger sections of DNA.

Until now, there has been no way to quickly and easily screen each of those mutations in their natural setting to see what role they may play in the development, progression, and treatment response of a tumor. Using a variant of CRISPR genome-editing known as prime editing, MIT researchers have now come up with a way to screen those mutations much more easily.

The researchers demonstrated their technique by screening cells with more than 1,000 different mutations of the tumor suppressor gene p53, all of which have been seen in cancer patients. This method, which is easier and faster than any existing approach, and edits the genome rather than introducing an artificial version of the mutant gene, revealed that some p53 mutations are more harmful than previously thought.

The researchers say this technique could also be applied to many other cancer genes, and could eventually be used for precision medicine, to determine how an individual patient’s tumor will respond to a particular treatment.

“In one experiment, you can generate thousands of genotypes that are seen in cancer patients, and immediately test whether one or more of those genotypes are sensitive or resistant to any type of therapy that you’re interested in using,” says Francisco Sanchez-Rivera, an MIT assistant professor of biology, a member of the Koch Institute for Integrative Cancer Research, and the senior author of the study.

MIT graduate student Samuel Gould is the lead author of the paper, which appears today in Nature Biotechnology.

Range-shifting fishes are climate-change losers, according to new research

Pouting (Trisopterus luscus)
Photo Credit: Diego Delso
(CC BY-SA 4.0 DEED)

The warming of the Earth’s oceans due to climate change is affecting where the world’s fishes live, eat and spawn — and often in ways that can negatively impact their populations. That’s according to a new paper in the journal Nature Ecology and Evolution.

The researchers write that populations that experience rapid-range shift decline noticeably, up to 50 per cent over a decade. The populations affected most are those living on the northern poleward edges of their species’ range.

“There is a conventional wisdom among many climate-change biologists that species that shift their ranges quickly by moving northward should provide a mechanism to sustain healthy populations — that shifting species should be climate-change winners. Our results show the exact opposite,” says paper co-author Jean-Philippe Lessard, a professor in the Department of Biology.

“Species that are shifting their range quickly experience little change in their population size in their core range. But some of them experience a major collapse in their populations at the northern edges.

“In fact, the population collapse is mostly driven by the northern poleward populations,” he adds. “We were expecting that many individuals from the core of the range would be moving up north due to climate change and maintain these northern populations. But the northern-edge populations are the ones most likely to collapse.”

Bees master complex tasks through social interaction

Bees can learn complex, multi-step tasks through social interaction, even if they cannot figure them out on their own.
Photo Credit: Michael Hodgins

In a groundbreaking discovery, bumblebees have been shown to possess a previously unseen level of cognitive sophistication.

 A new study, published in Nature, reveals that these bees can learn complex, multi-step tasks through social interaction, even if they cannot figure them out on their own. This challenges the long-held belief that such advanced social learning is unique to humans, and hints at the presence of key elements of cumulative culture in these insects.

Led by Dr Alice Bridges, postdoctoral researcher at the University of Sheffield, the research team designed a two-step puzzle box requiring bumblebees to perform two distinct actions in sequence to access a sweet reward at the end. The temporary reward was eventually taken away, and bees subsequently had to open the whole box before getting the treat. 

While individual bees struggled to solve the puzzle when starting from scratch, those allowed to observe a trained "demonstrator" bee readily learned the entire sequence – even the first step – while only getting a reward at the end.

You Didn’t See It Coming: the Spontaneous Nature of Turbulence

Photo Credit: Scientific Frontline 

We experience turbulence every day: a gust of wind, water gushing down a river or mid-flight bumps on an airplane.

Although it may be easy to understand what causes some kinds of turbulence — a felled tree in a river or a bear splashing around for salmon — there is now evidence that a very small disturbance at the start can have dramatic effects later. Instead of a tree, think of a twig — or even the swerving motion of a molecule.

University of California San Diego Chancellor’s Distinguished Professor of Physics Nigel Goldenfeld, along with his former student Dmytro Bandak, and Professors Alexei Mailybaev and Gregory Eyink, has shown in theoretical models of turbulence that even molecular motions can create large-scale patterns of randomness over a defined period of time. Their work appears in Physical Review Letters.

The butterfly effect

A butterfly flaps its wings in Brazil which later causes a tornado in Texas. Although we may commonly use the phrase to denote the seeming interconnectedness of our own lives, the term “butterfly effect” is sometimes associated with chaos theory. Goldenfeld said their work represents a more extreme version of the butterfly effect, first described by mathematician and meteorologist Edward Lorenz in 1969.

SwRI develops off-road autonomous driving tools focused on camera vision

SwRI is exploring using stereo cameras, or stereovision, as an alternative to lidar sensors in automated vehicles. SwRI's stereovision algorithms create disparity maps that estimate the depth of roadway features and obstacles. The left image shows how a conventional camera sees an off-road trail. The middle image shows a lidar image of the same trail. The right image shows a stereovision disparity map based on SwRI's algorithms, where colors indicate the distance of detected objects (yellow is near and blue is far). The gray/white in the lidar image suggests the outline of trees and a vehicle hood, but it does not indicate depth or distance.
Image Credit: Courtesy of Southwest Research Institute

Southwest Research Institute has developed off-road autonomous driving tools with a focus on stealth for the military and agility for space and agriculture clients. The vision-based system pairs stereo cameras with novel algorithms, eliminating the need for lidar and active sensors.

“We reflected on the toughest machine vision challenges and then focused on achieving dense, robust modeling for off-road navigation,” said Abe Garza, a research engineer in SwRI’s Intelligent Systems Division.

Through internal research, SwRI engineers developed a suite of tools known as the Vision for Off-Road Autonomy (VORA). The passive system can perceive objects, model environments and simultaneously localize and map while navigating off-road environments.

The VORA team envisioned a camera system as a passive sensing alternative to lidar, a light detection and ranging sensor, that emits active lasers to probe objects and calculate depth and distance. Though highly reliable, lidar sensors produce light that can be detected by hostile forces. Radar, which emits radio waves, is also detectable. GPS navigation can be jammed, and its signals are often blocked in canyons and mountains, which can limit agricultural automation.

More than flying cars: eVTOL battery analysis reveals unique operating demands

The operating phases of an eVTOL need varying amounts of power; some require the battery to discharge high amounts of current rapidly, reducing the distance the vehicle can travel before its battery must be recharged.
Illustration Credit: Andy Sproles/ORNL, U.S. Dept. of Energy

Researchers at the Department of Energy’s Oak Ridge National Laboratory are taking cleaner transportation to the skies by creating and evaluating new batteries for airborne electric vehicles that take off and land vertically. 

These aircraft, commonly called eVTOLs, range from delivery drones to urban air taxis. They are designed to rise into the air like a helicopter and fly using wing-borne lift like an airplane. Compared with helicopters, eVTOLs generally use more rotors spinning at a lower speed, making them both safer and quieter.

The airborne EV’s aren’t just flying cars, and ORNL researchers conclude that eVTOL batteries can’t just be adapted from electric car batteries. So far that has been the dominant approach to the technology, which is mostly in the modeling stage. ORNL researchers took a different tack by evaluating how lithium-ion batteries fare under extremely high-power draw. 

“The eVTOL program presents a unique opportunity for creating a brand-new type of battery with very different requirements and capabilities than what we have seen before," said Ilias Belharouak, an ORNL Corporate Fellow who guides the research. 

Rainforest’s next generation of trees threatened 30 years after logging

Logged forests have reduced seedling density, reducing the probability for the next generation to emerge.
Photo Credit David Bartholomew

Rainforest seedlings are more likely to survive in natural forests than in places where logging has happened – even if tree restoration projects have taken place, new research shows.

Scientists monitored over 5,000 seedlings for a year and a half in North Borneo.

They studied a landscape containing both natural forest and areas logged 30 years ago – some of which were recovering naturally, while some had been restored by methods including tree planting.

A drought had triggered “mast fruiting” across the region, with trees simultaneously dropping fruit en masse and new seedlings emerging.

At first, both natural forest and restored forest had similarly high numbers of seedlings, compared to naturally recovering forest – suggesting restoration activities enhanced fruit production.

But these benefits did not last: low seedling survival in the restored forest meant that, by the end of the study, similarly low numbers of seedlings remained in restored and naturally recovering forest. Seedling populations remained higher in natural forests.

Together, these results show that regeneration may be challenged by different factors depending on the restoration approach – seed availability in naturally recovering sites and seedling survival in sites where planted trees have matured. These differences may have longer-term implications for how forests can deliver key ecosystem services such as carbon sequestration.

Researchers discover a coral superhighway in the Indian Ocean

A coral reef in the Seychelles.
Photo Credit: Christophe Mason-Parker

Despite being scattered across more than a million square kilometers, new research has revealed that remote coral reefs across the Seychelles are closely related. Using genetic analyses and oceanographic modelling, researchers at Oxford University demonstrated for the first time that a network of ocean currents scatter significant numbers of larvae between these distant islands, acting as a ‘coral superhighway.’ These results have been published today in Nature Scientific Reports.

"This study couldn’t come at a timelier moment. The world is once again watching, as El Niño devastates coral reefs throughout the Indian Ocean. Now we know which reefs will be crucial to coral recovery, but we can’t pause in our commitment to reducing greenhouse gas emissions and stopping climate change."
Senior author of the study, Professor Lindsay Turnbull 
Department of Biology, University of Oxford

Dr April Burt (Department of Biology, University of Oxford, and Seychelles Islands Foundation), lead author of the study, said: ‘This discovery is very important because a key factor in coral reef recovery is larval supply. Although corals have declined alarmingly across the world due to climate change and a number of other factors, actions can be taken at local and national scale to improve reef health and resilience. These actions can be more effective when we better understand the connectivity between coral reefs by, for instance, prioritizing conservation efforts around coral reefs that act as major larval sources to support regional reef resilience.’

Maternal obesity may promote liver cancer

Obese mice pass on an altered microbiome to their offspring, which has an impact on liver health in adulthood and increases the risk of liver cancer. Normalising the intestinal microbiome reduces the risk of cancer. Specific families of bacteria are linked to tumour burden and liver inflammation.
Image Credit: Toso, Moeckli et al. 2024
CC-by-nc-nd

A team from the UNIGE and the HUG has revealed the role of the microbiota in the increased risk of developing liver disease in the offspring of mothers suffering from obesity.

Obesity, which could reach 50% of the population in certain developed countries by 2030, is a major public health concern. It not only affects the health of those who suffer from it, but could also have serious consequences for their offspring. Scientists at the University of Geneva (UNIGE) and the Geneva University Hospitals (HUG) have studied the impact of maternal obesity on the risk of developing liver disease and liver cancer. Using an animal model, the team discovered that this risk was indeed much higher in the offspring of mothers suffering from obesity. One of the main causes was the transmission of a disturbed intestinal microbiota from the mother, resulting in a chronic liver disease whose effects became apparent in adulthood. These results, which have yet to be confirmed in humans, are a warning signal and a call for action to limit the deleterious effect of obesity on children. This research is published in the journal JHEP Reports.

Researchers identify distinct sleep types and their impact on long-term health

Photo Credit: Sam Moghadam Khamseh

Poor sleep habits are strongly associated with long-term chronic health conditions, according to decades of research. To better understand this relationship, a team led by researchers in Penn State’s College of Health and Human Development identified four distinct patterns that characterize how most people sleep. These patterns are also predictive of long-term health, the researchers said.

Soomi Lee, associate professor of human development and family studies at Penn State, led a team in identifying these sleep patterns and their correlation to overall health. Their results were published in Psychosomatic Medicine.

Using a national sample of adults from the Midlife in the United States study, the team gathered data on approximately 3,700 participants’ sleep habits and their chronic health conditions across two time points 10 years apart. The data included self-reported sleep habits, including sleep regularity and duration, perceived sleep satisfaction and daytime alertness, as well as the number and type of chronic conditions.

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