Biotech

Researchers Engineer Bacteria To Produce Plastics (arstechnica.com) 39

An anonymous reader quotes a report from Ars Technica: [A] team of Korean researchers [describe] how they've engineered a bacterial strain that can make a useful polymer starting with nothing but glucose as fuel. The system they developed is based on an enzyme that the bacteria use when they're facing unusual nutritional conditions, and it can be tweaked to make a wide range of polymers. The researchers focused on the system bacterial cells use for producing polyhydroxyalkanoates (PHAs). These chemicals are formed when the bacterial cells continue to have a good supply of carbon sources and energy, but they lack some other key nutrients needed to grow and divide. Under these circumstances, the cell will link together small molecules that contain a handful of carbons, forming a much larger polymer. When nutritional conditions improve, the cell can simply break down the polymer and use the individual molecules it contained.

The striking thing about this system is that it's not especially picky about the identity of the molecules it links into the polymer. So far, over 150 different small molecules have been found incorporated into PHAs. It appears that the enzyme that makes the polymer, PHA synthase, only cares about two things: whether the molecule can form an ester bond (PHAs are polyesters), and whether it can be linked to a molecule that's commonly used as an intermediate in the cell's biochemistry, Coenzyme A. Normally, PHA synthase forms links between molecules that run through an oxygen atom. But it's also possible to form a related chemical link that instead runs through a nitrogen atom, like those found on amino acids. There were no known enzymes, however, that catalyze these reactions. So, the researchers decided to test whether any existing enzymes could be induced to do something they don't normally do. [...]

Overall, the system they develop is remarkably flexible, able to incorporate a huge range of chemicals into a polymer. This should allow them to tune the resulting plastic across a wide range of properties. And, considering the bonds were formed via enzyme, the resulting polymer will almost certainly be biodegradable. There are, however, some negatives. The process doesn't allow complete control over what gets incorporated into the polymer. You can bias it toward a specific mix of amino acids or other chemicals, but you can't entirely stop the enzyme from incorporating random chemicals from the cell's metabolism into the polymer at some level. There's also the issue of purifying the polymer from all the rest of the cell components before incorporating it into manufacturing. Production is also relatively slow compared to large-scale industrial production.
The findings have been published in the journal Nature Chemical Biology.
Biotech

Stem Cell Therapy Trial Reverses 'Irreversible' Damage to Cornea (newatlas.com) 15

Damaged corneas were repaired at a Harvard teaching hospital in a unique clinical trial, reports New Atlas: Since it's on the frontline of potential hazards from the outside world, the cornea features a population of limbal epithelial stem cells, which repair minor damage to keep the surface smooth and functional... The new study, conducted by scientists at Massachusetts Eye and Ear, investigated a new treatment called cultivated autologous limbal epithelial cells (CALEC). This involves removing stem cells from a patient's uninjured eye, growing their population in the lab for a few weeks, then surgically transplanting them into the injured eye.

The phase 1/2 trial recruited 14 patients to undergo the procedure, and followed them for 18 months afterwards... By the first checkup at three months, the corneas of seven (50%) of the participants had been completely restored. By the 12-month mark, that number had increased to 11 (79%) patients. Two other participants met the definition for partial success, so the team claims an overall success rate of 92% for CALEC.

Biotech

Gene-Edited Non-Browning Banana Could Cut Food Waste, Scientists Say (theguardian.com) 67

An anonymous reader quotes a report from The Guardian: Many of us have been guilty of binning a mushy, overripe banana -- but now scientists say they have a solution with the launch of a genetically engineered non-browning banana. The product is the latest in a series of gene-edited fruits and vegetables designed to have a longer shelf life. Scientists say the technology is emerging as a powerful new weapon against food waste, which occurs globally on an epic scale. The banana, developed by Tropic, a biotech company based in Norwich, is said to remain fresh and yellow for 12 hours after being peeled and is less susceptible to turning brown when bumped during harvesting and transportation.

The company has also developed a slow-ripening banana that has been approved in several countries, which it plans to launch later in the year. Other research teams are working on lettuce that wilts more slowly, bruise-resistant apples and potatoes and identifying the genes that determine how quickly grapes and blueberries shrivel. [...] The company worked out how to disable a gene responsible for the production of an enzyme called polyphenol oxidase, which causes browning. The same gene is silenced in Arctic apples, a genetically modified variety, which has been sold in the US since 2017, and blocking the production of polyphenol oxidase has been shown to work in tomatoes, melon, kiwifruits and mushrooms. In the bananas, Tropic made precise changes to existing genes without introducing foreign genetic material.
The report notes that an estimated 33% of the produce that is harvested worldwide is never consumed due to the short shelf-life of many fruit and vegetable products. Bananas are among the most thrown-away foods, with some 5 billion bananas tossed in the U.S. each year.
United Kingdom

How the British Broke Their Own Economy (theatlantic.com) 244

Britain, the birthplace of the Industrial Revolution, now suffers from its opposite: profound energy shortages and deep affordability crises [non-paywalled link]. A new report titled "Foundations" identifies the root cause -- "it is difficult to build almost anything, anywhere" in the UK.

Housing exemplifies this malaise. Since the 1990s, homeownership among young British workers has halved while housing prices doubled. The 1947 Town and Country Planning Act effectively nationalized development rights, requiring special permission for new construction and establishing restrictive "green belts." Despite Margaret Thatcher's market reforms, British house-building never recovered.

This constrictive policy has stymied potential growth beyond housing, Atlantic reports. Cambridge remains a small city despite biotech breakthroughs that might have transformed it into a major hub. Transit infrastructure languishes -- Leeds is Europe's largest city without a metro system. Energy production has collapsed, with per capita electricity generation now roughly one-third of America's.

Britain faces a self-imposed scarcity crisis. Environmental regulations, while beneficial, created a one-way system where lawsuits easily block development. As co-author Sam Bowman summarized: "Europe has an energy problem; the Anglosphere has a housing problem; Britain has both." The solution requires comprehensive reform-- overhauling the planning system, reducing anti-growth litigation, and encouraging energy production to unlock what the private sector "already wants to do."
Medicine

Anti-Aging Pill for Dogs Clears Key FDA Hurdle (msn.com) 48

San Francisco-based biotech startup Loyal says a drug it developed to increase dogs' lifespan "has passed a significant milestone on the way to regulatory approval," reports the Washington Post: The Food and Drug Administration certified the daily pill as having a "reasonable expectation of effectiveness" at extending senior dogs' lifespans. The regulator's Center for Veterinary Medicine still has to certify that the drug is safe and that Loyal can manufacture it at scale before vets can prescribe the pill to dogs 10 years or older that weigh 14 pounds or more. Loyal's CEO, Celine Halioua, estimates that the process should be complete by the end of 2025 and called the FDA's initial recognition "a key step" to extending dogs' lives...

In the past decade, a subculture of tech entrepreneurship has focused on helping people stave off death, hawking custom-made dietary supplements and $2,500 full-body MRIs and investing in the development of antiaging drugs, among many other efforts. According to data firm Pitchbook, about $900 million in venture capital has been poured into antiaging and longevity start-ups in the past 12 months. Loyal has raised more than $150 million in venture funding since its 2019 founding to develop lifespan-extending drugs initially focused on canines.

Launching veterinary drugs is in some ways easier than winning approval for human treatments. Because dogs and humans have evolved alongside one another, Halioua hopes to eventually apply her findings about pets to help prolong their owners' lives. "If we can successfully delay the onset and severity of age-related diseases in dogs, it's extremely compelling evidence that it will also do that in humans," Halioua said. The biological processes of aging unfold faster in dogs because they live such short lives, she said, helping researchers and entrepreneurs probe how they work.

"Loyal's pill is a result of research into how to mimic the life-extending benefit of caloric restriction without the appetite suppression," according to the article, "and without the need for an owner to restrict their dog's food.

"The drug aims to improve a dog's metabolic fitness, or the body's ability to convert nutrients into energy and regulate hormones, which declines in humans and canines with age..."
Biotech

Theranos Founder Elizabeth Holmes' Fraud Convictions Upheld (msnbc.com) 101

"Elizabeth Holmes' fraud conviction has been upheld by a federal appellate panel," writes Slashdot reader ClickOnThis. MSNBC reports: A three-judge panel of the 9th U.S. Circuit Court of Appeals on Monday affirmed the convictions, sentences and nine-figure restitution ordered against both Holmes and Theranos president, Ramesh "Sunny" Balwani. [...] Theranos was supposedly going to revolutionize medical laboratory testing with the ability to run fast, accurate and affordable tests with just a drop of blood from a finger prick. "But the vision sold by Holmes and Balwani was nothing more than a mirage," 9th Circuit Judge Jacqueline H. Nguyen wrote (PDF) for the panel, adding that the "grandiose achievements touted by Holmes and Balwani were half-truths and outright lies."

Holmes was convicted of crimes related to fraud against investors while the jury acquitted her or hung on other counts. Balwani was convicted on all counts at his trial. The federal panel rejected a slew of arguments from both defendants, including that their trials featured improper testimony from Theranos employees. While the ruling is a major setback for the defendants, they can further appeal to a fuller panel of 9th Circuit judges and the Supreme Court, which generally has broad discretion over whether to accept cases for review.

Biotech

AI Used To Design a Multi-Step Enzyme That Can Digest Some Plastics 33

Leveraging AI tools like RFDiffusion and PLACER, researchers were able to design a novel enzyme capable of breaking down plastic by targeting ester bonds, a key component in polyester. Ars Technica reports: The researchers started out by using the standard tools they developed to handle protein design, including an AI tool named RFDiffusion, which uses a random seed to generate a variety of protein backgrounds. In this case, the researchers asked RFDiffusion to match the average positions of the amino acids in a family of ester-breaking enzymes. The results were fed to another neural network, which chose the amino acids such that they'd form a pocket that would hold an ester that breaks down into a fluorescent molecule so they could follow the enzyme's activity using its glow.

Of the 129 proteins designed by this software, only two of them resulted in any fluorescence. So the team decided they needed yet another AI. Called PLACER, the software was trained by taking all the known structures of proteins latched on to small molecules and randomizing some of their structure, forcing the AI to learn how to shift things back into a functional state (making it a generative AI). The hope was that PLACER would be trained to capture some of the structural details that allow enzymes to adopt more than one specific configuration over the course of the reaction they were catalyzing. And it worked. Repeating the same process with an added PLACER screening step boosted the number of enzymes with catalytic activity by over three-fold.

Unfortunately, all of these enzymes stalled after a single reaction. It turns out they were much better at cleaving the ester, but they left one part of it chemically bonded to the enzyme. In other words, the enzymes acted like part of the reaction, not a catalyst. So the researchers started using PLACER to screen for structures that could adopt a key intermediate state of the reaction. This produced a much higher rate of reactive enzymes (18 percent of them cleaved the ester bond), and two -- named "super" and "win" -- could actually cycle through multiple rounds of reactions. The team had finally made an enzyme.

By adding additional rounds alternating between structure suggestions using RFDiffusion and screening using PLACER, the team saw the frequency of functional enzymes increase and eventually designed one that had an activity similar to some produced by actual living things. They also showed they could use the same process to design an esterase capable of digesting the bonds in PET, a common plastic.
The research has been published in the journal Science.
China

China To Develop Gene-Editing Tools, New Crop Varieties (reuters.com) 21

China issued guidelines on Friday to promote biotech cultivation, focusing on gene-editing tools and developing new wheat, corn, and soybean varieties, as part of efforts to ensure food security and boost agriculture technology. From a report: The 2024-2028 plan aims to achieve "independent and controllable" seed sources for key crops, with a focus to cultivate high-yield, multi-resistant wheat, corn and high-oil, high-yield soybean and rapeseed varieties. The move comes as China intensifies efforts to boost domestic yields of key crops like soybeans to reduce reliance on imports from countries such as the United States amid a looming trade war.
Biotech

Brain Implant That Could Boost Mood By Using Ultrasound To Go Under NHS Trial (theguardian.com) 48

An anonymous reader quotes a report from The Guardian: A groundbreaking NHS trial will attempt to boost patients' mood using a brain-computer-interface that directly alters brain activity using ultrasound. The device, which is designed to be implanted beneath the skull but outside the brain, maps activity and delivers targeted pulses of ultrasound to "switch on" clusters of neurons. Its safety and tolerability will be tested on about 30 patient in the 6.5 million-pound trial, funded by the UK's Advanced Research and Invention Agency (Aria).

[...] The latest trial will test a device developed by the US-based non-profit Forest Neurotech. In contrast to invasive implants, in which electrodes are inserted into a specific location in the brain, Forest 1 uses ultrasound to read-out and modify activity. Aria describes the device as "the most advanced BCI in the world" due to its ability to modify activity across multiple regions simultaneously. This widens potential future applications to a huge patient population affected by conditions such as depression, anxiety and epilepsy, which are all "circuit level" conditions rather than being localized in a specific brain region.

The NHS trial will recruit patients who, due to brain injury, have had part of their skull temporarily removed to relieve a critical buildup of pressure in the brain. This means the device can be tested without having to perform surgery. When placed beneath the skull, or in individuals with a skull defect, ultrasound can detect tiny changes in blood flow to produce 3D maps of brain activity with a spatial resolution of about 100 times that of a typical fMRI scan. The same implant can deliver focused ultrasound to mechanically nudge neurons towards firing, providing a way to remotely dial activity up at precise locations. Participants will wear the device on their scalp at the site of the skull defect for two hours. Their brain activity will be measured and researchers will test whether patients' mood and feelings of motivation can be reliably altered.

There are safety considerations, as ultrasound can cause tissue to heat up. Prof Elsa Fouragnan, a neuroscientist at the University of Plymouth, which is collaborating on the project, said: "What we're trying to minimize is heat. There's a safety and efficacy trade-off." She added that it would also be important to ensure that personality or decision-making were not altered in unintended ways -- for instance, making someone more impulsive. The study will run for three and a half years starting from March, with the first eight months focused on securing regulatory approval. If successful, Forest hopes to move into a full clinical trial for a condition such as depression.
Aimun Jamjoom, a consultant neurosurgeon at the Barking, Havering and Redbridge university hospitals NHS trust, who is leading the project, said: "[T]he ability to offer a safer form of surgery is very exciting. If you look at conditions like depression or epilepsy, [up to] a third of these patients just don't get better. It's those groups where a technology like this could be a life-changing solution."
Crime

Elizabeth Holmes Breaks Her Silence In First Interview From Prison (people.com) 138

Convicted Theranos founder, Elizabeth Holmes, had her first interview since being reported to prison in 2023, telling People magazine that she is still working on "research and inventions" in the healthcare space. Here's an excerpt from the article: Scheduled for release on April 3, 2032, Holmes says she hopes to travel with her family and to fight for reform of criminal justice system. She recently drafted an American Freedom Act bill -- a seven-page handwritten document -- to bolster the presumption of innocence and change criminal procedure. "This will be my life's work," says Holmes, adding that she is speaking out now as part of her mission to advocate on behalf of incarcerated persons and those ripped away from their children.

And, despite her global reputation as a biotech con artist who put lives at risk, she says she's continuing to write patents for new inventions and plans to resume her career in healthcare technology after her release. "There is not a day I have not continued to work on my research and inventions," she says. "I remain completely committed to my dream of making affordable healthcare solutions available to everyone."

For now, however, she is sustained by weekend visits from her family, when she can cuddle Invicta, watch William gather acorns in the prison yard and hold Evans's hand and briefly hug and kiss. (Conjugal visits are not allowed.) "It kills me to put my family through pain the way I do," she says. "But when I look back on my life, and these angels that have come into it, I can get through anything. It makes me want to fight for all of it."

Biotech

Technology For Lab-Grown Eggs Or Sperm On Brink of Viability, UK Watchdog Finds (theguardian.com) 99

An anonymous reader quotes a report from The Guardian: Bolstered by Silicon Valley investment, scientists are making such rapid progress that lab-grown human eggs and sperm could be a reality within a decade, a meeting of the Human Fertilization and Embryology Authority board heard last week (PDF). In-vitro gametes (IVGs), eggs or sperm that are created in the lab from genetically reprogrammed skin or stem cells, are viewed as the holy grail of fertility research. The technology promises to remove age barriers to conception and could pave the way for same-sex couples to have biological children together. It also poses unprecedented medical and ethical risks, which the HFEA now believes need to be considered in a proposed overhaul of fertility laws.

Peter Thompson, chief executive of the HFEA, said: "In-vitro gametes have the potential to vastly increase the availability of human sperm and eggs for research and, if proved safe, effective, and publicly acceptable, to provide new fertility treatment options for men with low sperm counts and women with low ovarian reserve." The technology also heralds more radical possibilities including "solo parenting" and "multiplex parenting." Julia Chain, chair of HFEA, said: "It feels like we ought to have Steven Spielberg on this committee," in a brief moment of levity in the discussion of how technology should be regulated. Lab-grown eggs have already been used produce healthy babies in mice -- including ones with two biological fathers. The equivalent feat is yet to be achieved using human cells, but US startups such as Conception and Gameto claim to be closing in on this prize.

The HFEA meeting noted that estimated timeframes ranged from two to three years -- deemed to be optimistic -- to a decade, with several clinicians at the meeting sharing the view that IVGs appeared destined to become "a routine part of clinical practice." The clinical use of IVGs would be prohibited under current law and there would be significant hurdles to proving that IVGs are safe, given that any unintended genetic changes to the cells would be passed down to all future generations. The technology also opens up myriad ethical issues.
Thompson said: "Research on IVGs is progressing quickly but it is not yet clear when they might be a viable option in treatment. IVGs raise important questions and that is why the HFEA has recommended that they should be subject to statutory regulation in time, and that biologically dangerous use of IVGs in treatment should never be permitted."

"This is the latest of a range of detailed recommendations on scientific developments that we are looking at to future-proof the HFE Act, but any decisions around UK modernizing fertility law are a matter for parliament."
Biotech

OpenAI Has Created an AI Model For Longevity Science (technologyreview.com) 33

OpenAI has developed a language model designed for engineering proteins, capable of converting regular cells into stem cells. It marks the company's first venture into biological data and demonstrates AI's potential for unexpected scientific discoveries. An anonymous reader quotes a report from MIT Technology Review: Last week, OpenAI CEO Sam Altman said he was "confident" his company knows how to build an AGI, adding that "superintelligent tools could massively accelerate scientific discovery and innovation well beyond what we are capable of doing on our own." The protein engineering project started a year ago when Retro Biosciences, a longevity research company based in San Francisco, approached OpenAI about working together. That link-up did not happen by chance. Sam Altman, the CEO of OpenAI, personally funded Retro with $180 million, as MIT Technology Review first reported in 2023. Retro has the goal of extending the normal human lifespan by 10 years. For that, it studies what are called Yamanaka factors. Those are a set of proteins that, when added to a human skin cell, will cause it to morph into a young-seeming stem cell, a type that can produce any other tissue in the body. [...]

OpenAI's new model, called GPT-4b micro, was trained to suggest ways to re-engineer the protein factors to increase their function. According to OpenAI, researchers used the model's suggestions to change two of the Yamanaka factors to be more than 50 times as effective -- at least according to some preliminary measures. [...] The model does not work the same way as Google's AlphaFold, which predicts what shape proteins will take. Since the Yamanaka factors are unusually floppy and unstructured proteins, OpenAI said, they called for a different approach, which its large language models were suited to. The model was trained on examples of protein sequences from many species, as well as information on which proteins tend to interact with one another. While that's a lot of data, it's just a fraction of what OpenAI's flagship chatbots were trained on, making GPT-4b an example of a "small language model" that works with a focused data set.

Once Retro scientists were given the model, they tried to steer it to suggest possible redesigns of the Yamanaka proteins. The prompting tactic used is similar to the "few-shot" method, in which a user queries a chatbot by providing a series of examples with answers, followed by an example for the bot to respond to. Although genetic engineers have ways to direct evolution of molecules in the lab, they can usually test only so many possibilities. And even a protein of typical length can be changed in nearly infinite ways (since they're built from hundreds of amino acids, and each acid comes in 20 possible varieties). OpenAI's model, however, often spits out suggestions in which a third of the amino acids in the proteins were changed. "We threw this model into the lab immediately and we got real-world results," says Retro's CEO, Joe Betts-Lacroix. He says the model's ideas were unusually good, leading to improvements over the original Yamanaka factors in a substantial fraction of cases.

Biotech

Startup Raises $200 Million To 'De-Extinct' the Woolly Mammoth, Thylacine and Dodo (venturebeat.com) 123

An anonymous reader quotes a report from VentureBeat: Colossal BioSciences has raised $200 million in a new round of funding to bring back extinct species like the woolly mammoth. Dallas- and Boston-based Colossal is making strides in the scientific breakthroughs toward "de-extinction," or bringing back extinct species like the woolly mammoth, thylacine and the dodo. [...] Since launching in September 2021, Colossal has raised $435 million in total funding. This latest round of capital places the company at a $10.2 billion valuation. Colossal will leverage this latest infusion of capital to continue to advance its genetic engineering technologies while pioneering new revolutionary software, wetware and hardware solutions, which have applications beyond de-extinction including species preservation and human healthcare.

"Our recent successes in creating the technologies necessary for our end-to-end de-extinction toolkit have been met with enthusiasm by the investor community. TWG Global and our other partners have been bullish in their desire to help us scale as quickly and efficiently as possible," said CEO Colossal Ben Lamm, in a statement. "This funding will grow our team, support new technology development, expand our de-extinction species list, while continuing to allow us to carry forth our mission to make extinction a thing of the past."
Here's a summary of the startup's progress on its efforts to bring back the woolly mammoth, thylacine and the dodo:

Woolly Mammoth De-extinction Progress
- Generated chromosome-scale reference genomes for elephants and the first de novo assembled mammoth genome
- Acquired and aligned 60+ ancient mammoth genomes and 30+ genomes of extant elephant species, improving mammoth-specific variant accuracy
- Derived pluripotent stem cells for Asian elephants, advancing reproductive technologies essential for de-extinction

Thylacine De-extinction Progress
- Created a 99.9% complete ancient genome for the thylacine using long-read and RNA sequencing
- Assembled telomere-to-telomere genomes of dasyurid species to understand evolutionary relationships and support conservation of marsupials
- Progress in genomics and reproductive technologies positions Colossal ahead of schedule on critical de-extinction steps

Dodo De-extinction Progress
- Completed high-coverage genomes for the dodo, its relatives, and the critically endangered manumea
- Developed tools for avian genome engineering, including techniques for craniofacial gene-editing and primordial germ cell cultivation
- Significant advances in avian-specific genetic techniques are driving progress toward dodo restoration and bird conservation
Biotech

Neuralink Implants Third Brain Chip. Plans '20 or 30' This Year, Eventually 'Blindsight' Devices (yahoo.com) 111

"Neuralink Corp.'s brain-computer device has been implanted in a third patient," reports Bloomberg, "and the company has plans for about 20 to 30 more implants in 2025, founder Elon Musk said."

In an interview streamed on X.com, Musk says "We've got now three humans with Neuralinks implanted and they're all working well," according to The Times of India: "We upgraded the devices, they'll have more electrodes, basically higher bandwidth, longer battery life and everything. So, expect 20 or 30 patients this year with the upgraded Neuralink devices...."

"[O]ur next part will be Blindsight devices where even if somebody has lost both eyes or has lost the optic nerve, we can interface directly with the visual cortex in the brain and enable them to see. We already have that working in monkeys," Musk added.

Science

Scientists Explore Longevity Drugs For Dogs That Could Also 'Extend Human Life' (theguardian.com) 80

U.S. biotech startup Loyal plans to launch a lifespan-extending drug for dogs in early 2025, potentially offering insights into human longevity. The San Francisco-based company has secured $125 million in funding for LOY-002, a beef-flavored daily pill designed to extend canine lifespans by at least one year. The drug works by targeting age-related metabolic changes and insulin regulation, according to Loyal CEO Celine Halioua.

Simultaneously, the Dog Aging Project is studying rapamycin, an immunosuppressant drug, which preliminary research suggests could add three years to dogs' lives. Researchers believe these canine studies could accelerate human longevity research, though experts note the lack of standardized aging biomarkers remains a significant hurdle for human trials.
Biotech

Scientists Have Finally Found the Gene That Gives Cats Orange Fur (science.org) 57

Slashdot reader sciencehabit writes: Most orange cats are boys, a quirk of feline genetics that also explains why almost all calicos and tortoiseshells are girls. Scientists curious about those sex differences—or perhaps just cat lovers—have spent more than 60 years unsuccessfully seeking the gene that causes orange fur and the striking patchwork of colors in calicos and tortoiseshells. Now, two teams have independently found the long-awaited mutation and discovered a protein that influences hair color in a way never seen before in any animal... Using skin samples collected from various cats, the researchers were able to hone in a mutation on the X chromosome that impacts how much of a protein a gene called Arhgap36 produces. Increasing the amount of the Arhgap36 in pigment producing cells called melanocytes activates a molecular pathway that produces a light red pigment.
"Scanning a database of 188 cat genomes, Barsh's team found every single orange, calico, and tortoiseshell cat had the exact same mutation," writes Science magazine. "The group reports the discovery this month on the preprint server bioRxiv. A separate study, also posted to bioRxiv this month, confirms these findings... They also found that skin from calico cats had more Arghap36 RNA in orange regions than in brown or black regions." Arhgap36's inactivation pattern in calicos and tortoiseshells is typical of a gene on the X chromosome, says Carolyn Brown [a University of British Columbia geneticist who was not involved in either study], but it's unusual that a deletion mutation would make a gene more active, not less. "There is probably something special about cats." Experts are thrilled by the two studies. "It's a long-awaited gene," says Leslie Lyons, a feline geneticist at the University of Missouri. The discovery of a new molecular pathway for hair color was unexpected, she says, but she's not surprised how complex the interactions seem to be. "No gene ever stands by itself."

Lyons would like to know where and when the mutation first appeared: There is some evidence, she says, that certain mummified Egyptian cats were orange. Research into cat color has revealed all kinds of phenomena, she says, including how the environment influences gene expression. "Everything you need to know about genetics you can learn from your cat."

Science

Scientists Announce Progress Toward Ambitious Atlas of Human Cells (reuters.com) 5

Scientists unveiled on Wednesday the first blueprint of human skeletal development as they make progress toward the goal of completing a biological atlas of every cell type in the body to better understand human health and diagnose and treat disease. From a report: The work is part of the ongoing Human Cell Atlas project that was begun in 2016 and involves researchers around the world. The human body comprises roughly 37 trillion cells, with each cell type having a unique function. The researchers aim to have a first draft of the atlas done in the next year or two.

Aviv Regev, founding co-chair of the project and currently executive vice president and head of research and early development at U.S. biotech company Genentech, said the work is important on two levels. "First of all, it's our basic human curiosity. We want to know what we're made of. I think humans have always wanted to know what they're made of. And, in fact, biologists have been mapping cells since the 1600s for that reason," Regev said. "The second and very pragmatic reason is that this is essential for us in order to understand and treat disease. Cells are the basic unit of life, and when things go wrong, they go wrong with our cells, first and foremost," Regev said.

Biotech

23andMe To Lay Off 40% of Its Workforce, Discontinue All Therapy Programs (bbc.com) 72

The genetic testing company 23andMe announced it will cut 40% of its workforce, or 200 jobs, and halt the work on therapies it was developing. As the BBC notes, the company is fighting for survival after hackers gained access to personal information of millions of its users, causing the stock to crater by more than 70%. All seven of its independent directors also resigned in September, following a protracted negotiation with founder and Chief Executive Anne Wojcicki over her plan to take the company private. The BBC reports: On Tuesday, the company warned investors of "substantial doubt" about its ability to continue operating, as it reported that revenue had fallen to $44 million between July and September compared to $50 million in the same period last year. Losses fell to $59 million from $75 million. The job cuts are expected to lead to one-off costs of $12 million, including severance pay, for the plan that will result in savings of $35 million. "We are taking these difficult but necessary actions as we restructure 23andMe and focus on the long-term success of our core consumer business and research partnerships," Ms Wojcicki said.

The company also said it is considering what to do with the therapies it had in development, including licensing or selling them. 23andMe is a giant of the growing ancestor-tracing industry. It offers genetic testing from DNA, with ancestry breakdown and personalised health insights. Its customers include famous names, from rapper Snoop Dogg to multi-billionaire investor Warren Buffett. The company was valued at roughly $3.5 billion when it listed on the Nasdaq stock exchange in 2021 and its share price peaked at $17.65. But they have since tumbled and are currently trading at less than $5.

Biotech

Researchers Develop New Method That Tricks Cancer Cells Into Killing Themselves (stanford.edu) 21

Our bodies divest themselves of 60 billion cells every day through a natural process called "apoptosis". So Stanford medicine researchers are developing a new approach to cancer therapy that could "trick cancer cells into disposing of themselves," according to announcement from Stanford's medical school: Their method accomplishes this by artificially bringing together two proteins in such a way that the new compound switches on a set of cell death genes... One of these proteins, BCL6, when mutated, drives the blood cancer known as diffuse large cell B-cell lymphoma... [It] sits on DNA near apoptosis-promoting genes and keeps them switched off, helping the cancer cells retain their signature immortality.

The researchers developed a molecule that tethers BCL6 to a protein known as CDK9, which acts as an enzyme that catalyzes gene activation, in this case, switching on the set of apoptosis genes that BCL6 normally keeps off. "The idea is, Can you turn a cancer dependency into a cancer-killing signal?" asked Nathanael Gray, PhD, co-senior author with Crabtree, the Krishnan-Shah Family Professor and a chemical and systems biology professor. "You take something that the cancer is addicted to for its survival and you flip the script and make that be the very thing that kills it...."

When the team tested the molecule in diffuse large cell B-cell lymphoma cells in the lab, they found that it indeed killed the cancer cells with high potency. They also tested the molecule in healthy mice and found no obvious toxic side effects, even though the molecule killed off a specific category of of the animals' healthy B cells, a kind of immune cell, which also depend on BCL6. They're now testing the compound in mice with diffuse large B-cell lymphoma to gauge its ability to kill cancer in a living animal. Because the technique relies on the cells' natural supply of BCL6 and CDK9 proteins, it seems to be very specific for the lymphoma cells — the BCL6 protein is found only in this kind of lymphoma cell and in one specific kind of B cell. The researchers tested the molecule in 859 different kinds of cancer cells in the lab; the chimeric compound killed only diffuse large cell B-cell lymphoma cells.

Scientists have been trying to shut down cancer-driving proteins, one of the researchers says, but instead, "we're trying to use them to turn signaling on that, we hope, will prove beneficial for treatment."

The two researchers have co-founded the biotech startup Shenandoah Therapeutics, which "aims to further test this molecule and a similar, previously developed molecule," according to the article, "in hopes of gathering enough pre-clinical data to support launching clinical trials of the compounds.

"They also plan to build similar molecules that could target other cancer-driving proteins..."
Science

Eating Less Can Lead To a Longer Life: Massive Study in Mice Shows Why (nature.com) 58

Cutting calorie intake can lead to a leaner body -- and a longer life, an effect often chalked up to the weight loss and metabolic changes caused by consuming less food. Now, one of the biggest studies of dietary restrictions ever conducted in laboratory animals challenges the conventional wisdom about how dietary restriction boosts longevity. From a report: The study, involving nearly 1,000 mice fed low-calorie diets or subjected to regular bouts of fasting, found that such regimens do indeed cause weight loss and related metabolic changes. But other factors -- including immune health, genetics and physiological indicators of resiliency -- seem to better explain the link between cutting calories and increased lifespan. "The metabolic changes are important," says Gary Churchill, a mouse geneticist at the Jackson Laboratory in Bar Harbor, Maine, who co-led the study. "But they don't lead to lifespan extension."

To outside investigators, the results drive home the intricate and individualized nature of the body's reaction to caloric restriction. "It's revelatory about the complexity of this intervention," says James Nelson, a biogerontologist at the University of Texas Health Science Center in San Antonio. The study was published today in Nature by Churchill and his co-authors, including scientists at Calico Life Sciences in South San Francisco, California, the anti-ageing focused biotech company that funded the study. Scientists have long known that caloric restriction, a regimen of long-term limits on food intake, lengthens lifespan in laboratory animals. Some studies have shown that intermittent fasting, which involves short bouts of food deprivation, can also increase longevity.

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