Natural mutations hamper gene drives

Efforts to spread new gene variants across insect populations face genetic hurdles.

Natural genetic variation is likely to stymie gene drives, which are designed to deploy specific heritable mutations across a population of organisms, such as disease-carrying insects. 

Researchers have recently developed gene drives based on the CRISPR–Cas9 gene-editing system for fruit flies and malaria-transmitting mosquitoes. A team led by Michael Wade at Indiana University in Bloomington modelled whether natural genetic variation in an agricultural pest called the red flour beetle (Tribolium castaneum) could prevent the spread of a CRISPR-based gene drive. The team found that many wild beetle populations harbour genetic variants that, even when rare, would make beetles immune to gene drives that target three different genes.

Inbreeding, which is common in some disease-carrying insects, increases the prevalence of mutations that can inactivate gene drives.

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Highlights from recent research


Tumour cells avoid crowds

Key chemical signals drive cancer cells to migrate as their density increases. 

Densely packed tumour cells produce molecules that help them to migrate and spread, or metastasize, throughout the body.

Daniele Gilkes at Johns Hopkins University in Baltimore, Maryland, and her colleagues studied metastatic human sarcoma and carcinoma cells. As the rapidly proliferating cells reached higher densities inside a 3D collagen matrix, they moved around more and at greater speeds. Low-density cell samples also became highly motile when exposed to liquid medium taken from the high-density samples. The researchers found that crowded cancer cells boosted production of two immune molecules, IL-6 and IL-8, which stimulate biochemical pathways that enhance tumour migration. In a mouse model of breast cancer, treating animals with experimental cancer drugs that blocked receptors for IL-6 and IL-8 reduced the spread of tumour cells to the lungs, liver and lymph nodes, compared with untreated animals.

The results suggest potential new drug targets for suppressing tumour metastasis in patients, the authors say.

The Aliso Canyon gas field in California was the site of a huge methane gas leak in 2015 -- the single largest man-made greenhouse gas emission event in US history.

The Aliso Canyon gas field in California was the site of a huge methane gas leak in 2015 -- the single largest man-made greenhouse gas emission event in US history. Credit: Dean Musgrove/Reuters


The risky business of stored gas

Natural gas storage wells at risk of leaking are more widespread across the United States than previously thought.

One in five natural-gas storage wells in the United States are so old that they could accidentally release harmful gas.

In 2015, almost 100,000 tonnes of methane leaked into the atmosphere from a well at Aliso Canyon in California after its protective casing failed. The gas caused illness and forced the evacuation of thousands of local residents. Drew Michanowicz at Harvard T. H. Chan School of Public Health in Boston, Massachusetts, and his colleagues gathered data on more than 14,000 active natural-gas storage wells across the continental United States and identified around 2,700 wells that were originally built for oil or gas production and not for high-pressure gas storage. About 200 wells were more than a century old.

A census of old and obsolete storage wells could help the US energy industry to avoid disasters like that at Aliso Canyon, the authors say.

Explosive origins for antimatter

White dwarf supernovae might be generating positrons.

Most of the antimatter in interstellar space could be created in the merger and resulting explosions of white dwarfs — the inert remnants of Sun-like stars.

In our Galaxy, there are 1043 annihilations every second between electrons and their antimatter counterparts, positrons — but how the positrons are generated remains unknown. A team led by Roland Crocker of the Australian National University in Canberra calculated that supernovae resulting from mergers of white dwarfs between 3 billion and 6 billion years old could be generating the positrons. Such explosions should yield radioactive titanium-44, which would emit positrons at the observed rate.

The production of titanium-44 could also explain why calcium-44 — one of its decay products — is relatively abundant in the Solar System.


Attacking drug-resistant tumours in the brain

Targeting a specific protein could cripple cancers that have spread.

Human breast-cancer cells implanted in the brains of mice resist therapy by activating a protein called HER3, suggesting a new target for attacking tumours that have spread to the brain. 

Cancer therapies that home in on specific proteins often fail to reign in tumours that have spread, or metastasized, to the brain. To find out why, Rakesh Jain at Massachusetts General Hospital in Boston, Jeffrey Engelman, now at the Novartis Institute for Biomedical Research in Cambridge, Massachusetts, and their colleagues studied mice that had human breast-cancer cells implanted in their brains.  Those cells had previously been treated with drugs that target a cancer-promoting protein called HER2, to mimic how the cells would have been treated in humans with breast cancer. 

They found that brain cells surrounding the resulting tumours caused the growths to become drug-resistant. Such tumours showed increased expression of HER3, and samples of human brain metastases also had elevated levels of this protein. Treatment with antibodies that inhibit HER3 sensitized the tumours to therapy. 


Early farmers bred with hunter-gatherers

Ancient human DNA suggests that the first farmers moved across Europe and closely integrated with hunter-gatherers.

Farming spread through Eurasia several thousand years ago, but whether that was due to the movement and displacement of people or to the exchange of ideas has been hotly debated. Michael Hofreiter at the University of Potsdam in Germany and his colleagues sequenced DNA from human remains found in Romania and Spain, dating from 5,400 to 9,100 years ago.

They found that the older Romanian samples, which pre-date the arrival of farmers to the region, were genetically similar to those from Spain and to published hunter-gatherer sequences from Northern Europe. However, the most recent Romanian sample showed a mixture of genes from hunter-gatherer and Anatolian farming populations, suggesting that arriving farmers bred over many generations with local hunter-gatherers in the Danube basin. 

Farming communities are thought to have displaced hunter-gatherers in Western Europe, but these data show that farther east, they interacted closely, despite large cultural differences. The switch to farming, at least in some parts of Europe, was driven by the spread of both people and ideas, the authors conclude.

Blood test reveals signs of pancreatic cancer

Detecting proteins on small sacs shed by tumours could improve diagnosis.

By testing patients’ blood for five protein biomarkers, researchers have succeeded in diagnosing pancreatic cancer with an accuracy of 84%. By comparison, testing for individual markers achieved only 63% to 72% accuracy.

Pancreatic cancer is a particular deadly form of the disease, prompting efforts to improve early detection. One way to spot cancer is to look for small membrane-bound sacs called extracellular vesicles, which are shed by tumours, in the bloodstream. Ralph Weissleder at the Massachusetts General Hospital in Boston and his colleagues developed a system that could rapidly screen blood samples for these vesicles. Samples of vesicles isolated from blood are placed on a chip that contains a porous gold surface. The system senses changes in the colour of light shining through the samples and the pores when the vesicles bind to specific antibodies that are attached to the gold surface. By comparing samples from people with and without pancreatic cancer, the team identified a signature of five proteins on the surface of the vesicles that indicated the presence of the disease.

This method could offer a rapid, low-cost way of improving the diagnosis of pancreatic cancer, the authors suggest. 

This holographic image of a fictional dinosaur from the movie Jurassic World was made using a nanometre-scale quantum material.

This holographic image of a fictional dinosaur from the movie Jurassic World was made using a nanometre-scale quantum material. Credit: Z. Yue et al./Nat. Commun. (CC BY 4.0)

Optics and photonics

Nano-hologram made from the thinnest material yet

Consumer devices could one day generate holograms.

The creation of a hologram using a 25-nanometre-thick material could pave the way to displaying 3D images on small devices such as smartphones.

Materials generate images that appear 3D by diffracting light and creating interference patterns, but the materials are typically hundreds of nanometres thick — too bulky for use in modern electronic devices. Min Gu of the RMIT University in Melbourne, Australia, and his colleagues found that a particular quantum material can act as a resonant cavity, which enhances the diffraction of light passing through it. The team used the material — just tens of nanometres thick — to create a holographic image of the fictional dinosaur Indominus rex from the film Jurassic World.

Slim holographic materials could one day be integrated into electronic devices, and have the potential to increase the capacity of data-storage devices, the authors say.

Baleen whales such as this humpback whale (Megaptera novaeangliae) evolved large body sizes as their food supplies changed millions of years ago.

Baleen whales such as this humpback whale (Megaptera novaeangliae) evolved large body sizes as their food supplies changed millions of years ago. Credit: Tony Wu/NPL


Why baleen whales grew so big

Shifting winds and food supplies favoured the evolution of huge whales three million years ago.

Blue whales (Balaenoptera musculus) and other baleen whales are known for their size, but their ancestors weren’t so gargantuan. Graham Slater at the University of Chicago in Illinois and his colleagues modelled the evolution of whales using data on body length for both living and extinct whales. They conclude that baleen whales more than ten metres long diversified about three million years ago, at around the time when shifting winds started to draw colder water brimming with prey up from the deep ocean. 

Larger whales were probably more efficient at moving between and rapidly feeding on dense but isolated patches of prey than their smaller counterparts, the authors suggest.

This 3.3 million year old Australopithecus afarensis spine is surprisingly modern-looking.

This 3.3 million year old Australopithecus afarensis spine is surprisingly modern-looking. Credit: Zeresenay Alemseged


Ancient hominin spine shows modern human features

A 3.3-million-year-old fossil suggests key adaptations for walking occurred earlier than thought.

Compared with great apes, humans have one fewer rib-bearing vertebrae in the middle back. This is an adaptation for efficient bipedal walking but is found in few early hominin fossils, so it is unclear when such changes emerged. A team led by Carol Ward at the University of Missouri in Columbia analysed Australopithecus afarensis remains from Ethiopia that include a complete upper and middle spine. The fossil — which is named Selam and is that of a young child — had the same number of neck and middle back vertebrae as modern humans. 

But the anatomical transition between the middle and lower back occurred higher in Selam’s spinal column than in modern humans. The change in spinal structure may have occurred in Homo species, which emerged after A. afarensis, as an adaptation to long-distance walking and running, the authors say.

Astronomy and astrophysics

Planet-like object is also star-like

A celestial planet-like object and its dusty disk blur the line between planets and stars.

Planets, young stars, and failed stars known as brown dwarfs may have more in common than astronomers thought.

Amelia Bayo at the University of Valparaiso in Chile and her colleagues studied OTS44, a planet-like object thought to be 160 parsecs away that is about 12 times the mass of Jupiter and is surrounded by a disk of swirling dust. Using the high-resolution Atacama Large Millimeter/submillimeter Array in Chile, the authors calculated the mass of the disk.

The relative difference in mass between it and OTS44 is similar to mass differences measured for brown dwarfs and young stars and the dust clouds that surround them. This suggests that OTS44 formed in a similar way to these objects, from a collapsing cloud of debris — which is odd, because it was thought to be too small to have formed this way.

The inset image was projected onto a plate of pigment-producing Escherichia coli, causing the bacteria to make the image on the right.

The inset image was projected onto a plate of pigment-producing Escherichia coli, causing the bacteria to make the image on the right. Credit: J. Fernandez-Rodriguez et al./Nat. Chem. Biol.

Synthetic biology

Colour pictures made in bacterial film

Engineered E. coli produce red, green and blue pigments based on light exposure.

A genetic system that contains 18 genes and other elements has allowed Escherichia coli to make different pigments according to the colour of light — red, green or blue — the bacteria are exposed to.

Christopher Voigt and his colleagues at the Massachusetts Institute of Technology in Cambridge designed the system to include genes encoding proteins that are sensitive to different wavelengths of light. Bacteria with the system produce pigments that are the same colour as the light they are exposed to. The team grew E. coli on a plate while projecting a coloured image onto it. Less than 24 hours later, the pigments generated formed an image that was identical to the original.

Engineering bacteria to recognize a variety of colours could be useful in fine-tuning the control of microbes from afar in a variety of biomedical applications, the authors say.


A pro-cancer protein that’s anti-pain

An immune-suppressing molecule is linked to pain sensitivity in mice.

A molecule made by some cancers and targeted by certain immunotherapies also blocks pain in mice.

Ru-Rong Ji at Duke University Medical Center in Durham, North Carolina, Yu-Qiu Zhang at Fudan University in Shanghai, China, and their colleagues studied the effects of PD-L1. This protein is inhibited by certain cancer immunotherapies because it suppresses the immune response to  tumours. The researchers found that PD-L1 is also made by healthy tissues such as the skin and spinal cord.  Inhibiting PD-L1 or deleting its receptor made mice more sensitive to pain. Conversely, injecting PD-L1 into rodents temporarily increased pain thresholds near the injection site, and reduced chronic pain caused by nerve injury. The activity of PD-L1 and its receptor dampens electrical activity in spinal nerve cells that transmit pain signals.

The findings could lead to new analgesics, the authors suggest. They add that patients being treated with cancer immunotherapies that block PD-L1 might need to have their pain levels monitored.


New target for cancer immunotherapy

An antibody that inhibits regulatory immune cells boosts anticancer responses in mice.

Regulatory T cells help to modulate the immune system, and those that express a protein called LAP are particularly potent suppressors of immune responses to cancer. The cells have been linked to poor outcomes in people with the disease. Howard Weiner at Brigham and Women’s Hospital in Boston, Massachusetts, and his colleagues have found a way to target these cells with an antibody that lowers LAP levels.

Treatment with the antibody diminished tumour growth in mice, and improved the effectiveness of an anticancer vaccine. Four months after treatment, the antibody had increased the number of CD8+ T cells, which are involved in immune memory. This suggests that inhibiting LAP could enhance the immune system’s ability to quickly recognize and respond to cancer cells.

The damselfish Dascyllus marginatus swims above the coral Stylophora pistillata.

The damselfish Dascyllus marginatus swims above the coral Stylophora pistillata. Credit: Nur Garcia-Herrera


Fish boost coral photosynthesis

The flicking fins of damselfish may be the reason for enhanced coral growth.

Damselfish living in and around coral reefs could be boosting coral growth by increasing ventilation.

Coral reefs and damselfish species have a mutually beneficial relationship. The fish hide from predators among coral branches, and in turn, they clean coral surfaces and protect them from predators. Corals that host the fish are known to grow faster. To learn why, Nur Garcia-Herrera at the Leibniz Center for Tropical Marine Ecology in Bremen, Germany, and her colleagues captured Dascyllus marginatus damselfish and colonies of the branching coral Stylophora pistillata in the northern Red Sea, and studied them in the lab. 

They found that fish living between the coral branches increased coral photosynthesis, probably because the fishes’ fin movements improved ventilation. Video cameras placed near coral reefs in the wild revealed that the fish spend up to 34% of daylight hours within the coral. The researchers estimate that the fish boost coral photosynthesis by 3–6%.

Tasmanian devils (Sarcophilus harrisii) transmit cancer to each other through biting.

Tasmanian devils (Sarcophilus harrisii) transmit cancer to each other through biting. Credit: D. Parer & E. Parer-Cook/Minden Pictures/FLPA


Transmissible tumours target the fittest devils

Social success may boost risk of Tasmanian devil facial tumour disease.

Many diseases tend to target the weakest animals in a population, but in Tasmanian devils, an aggressive transmissible cancer that causes devil facial tumour disease seems to infect the fittest. Animals that eventually become infected survive at a higher rate and reproduce more before dying of the disease than devils that don’t get the cancer.

Konstans Wells of Griffith University in Brisbane, Australia, and his colleagues used 10 years of data on 518 Tasmanian devils (Sarcophilus harrisii) in western Tasmania to build a model of survival, reproduction and cancer in the animals. They found that devils with cancer were fitter than those without tumours, and that animals with small tumours had higher average survival rates than those that were never infected. Female cancer hosts reproduced 1.3 times on average before dying, compared to 0.7 times for uninfected females, and had more offspring per litter.

The disease is spread through biting during mating and other interactions, and so the fittest animals could be becoming infected more often because they tend to be more socially dominant. The team’s data also suggest a decline in the rate of infection and transmission since 2012, which may be due to increasing disease resistance.

Moss samples collected from Ardley Island and other sites on the Antarctic Peninsula showed increasing moss growth due to rising temperatures.

Moss samples collected from Ardley Island and other sites on the Antarctic Peninsula showed increasing moss growth due to rising temperatures. Credit: Dan Charman

Climate change

Antarctica is going green

Global warming has increased moss growth at sites across the Antarctic Peninsula over the past half-century.

Much of Antarctica is covered in ice, but parts of its peninsula are instead blanketed in moss. Each year, more moss grows over the top of the previous season’s growth, providing a record of moss health over thousands of years. 

Matthew Amesbury at the University of Exeter, UK, and his colleagues isolated moss-bank cores dating back 150 years from three sites across the peninsula. They found that since 1950 moss growth and accumulation have increased markedly at all sites. This shift is probably due to the increasing global temperatures associated with climate change. 

Continued warming will probably trigger large-scale changes to Antarctic terrestrial ecosystems, the authors suggest.

Nanoscience and technology

Nanoprobe detects the force of swimming bacteria

The optical fibre is several times more sensitive than other techniques.

A thin optical fibre can detect the minuscule forces generated by swimming bacteria with a sensitivity at least 10 times greater than that achieved by atomic force microscopes. 

Probes used in atomic force microscopy are often bulky, and some other force detectors have low resolution. Donald Sirbuly and his colleagues at the University of California, San Diego, made a compact device from a tin dioxide fibre 200-400 nanometres in diameter, which they covered in a polymer and dotted with gold nanoparticles. The particles interact with light passing down the fibre. When forces — such as those generated by nearby swimming bacteria or beating heart cells — push the gold particles into the polymer, the interaction increases. This boosts the intensity of the light scattered by the nanoparticles. 

Using a microscope to pick up these changes, the authors detected forces as small as 160 femtonewtons (1 femtonewton is 10−15 newtons). The team plans to use the device to measure the behaviour of single cells.

A device with sticky gripper can lift a variety of irregularly shaped objects.

A device with sticky gripper can lift a variety of irregularly shaped objects. Credit: Sukho Song


Sticky gripper can lift flasks and tomatoes

A gecko-inspired adhesive could help robots to climb bumpy walls and grasp fragile objects.

The hairs that make geckos’ feet sticky have inspired the invention of adhesives for flat surfaces, but creating strong adhesives that can grab complex, 3D objects has proved a challenge. 

Metin Sitti at the Max Planck Institute for Intelligent Systems in Stuttgart, Germany, and his colleagues spread elastic microfibres, or ‘hairs’, across a soft, stretchy membrane, allowing it to mould and stick to a surface. The team attached this to a ‘gripper’ layer. Reducing the pressure inside the gripper spreads the load evenly across the sticky membrane, strengthening the bond between it and the target object. Changing the pressure in the system increased the membrane’s ‘stickiness’ 14-fold, allowing the device to suspend a variety of hard and soft objects, from fluid-filled flasks to tomatoes.

Materials science

3D-printed device makes clean steam

The evaporator uses solar energy to efficiently purify water.

Most evaporators that use solar heating rely on lenses or mirrors to concentrate sunlight, which makes it difficult to stop heat being lost to the environment and reduces efficiency. Liangbing Hu and his colleagues at the University of Maryland in College Park built a device using a 3D-printed material made of carbon nanotubes and graphene oxide, which absorbs 97% of incoming sunlight and rapidly warms up. This layer sits on a box with no bottom, which was 3D-printed using porous graphene oxide and nanostructured cellulose. When placed in shallow water, the walls of the box wick water to the top layer, where it is heated and escapes as steam.

The device used 85.6% of the absorbed energy to generate steam, which is one of the highest efficiencies achieved by evaporators. The approach could help to ease shortages in areas where water has to be sterilized or desalinated, the authors say.