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Project to create yeast with fully synthetic genome nears completion

An international effort to create yeast cells with a fully synthetic genome is nearing completion, with the eventual aim of unraveling the mysteries of…



An international effort to create yeast cells with a fully synthetic genome is nearing completion, with the eventual aim of unraveling the mysteries of genomes and ushering in a tool for producing complex medicines.

Scientists hope to create the synthetic organism by stitching together small pieces of DNA into artificial chromosomes and trimming out some genetic fat in the process.

The Synthetic Yeast Genome Project — abbreviated Sc2.0 — dates back more than 15 years. Now, in the consortium’s biggest update since revealing five synthetic chromosomes in 2017, its scientists published 10 papers describing the creation of most of the remaining chromosomes, along with a wholly new one that does not exist in nature.

Jef Boeke

“We’ve got all 16 chromosomes completely synthesized,” Jef Boeke, a synthetic biologist at NYU Langone Health and leader of the project, told Endpoints News. The group is still working on bringing those chromosomes, each in different yeast strains, together into a single organism. “We’re about a year or two away from completing that whole thing,” Boeke said.

Scientists at the J. Craig Venter Institute, led by the eponymous geneticist who rose to fame as a leader of the Human Genome Project, have previously built viruses and bacteria from synthetic DNA. But the Sc2.0 yeast would be the most complex synthetic organism yet. And since yeast is more closely related to animals than bacteria, it’s a better stepping stone for answering questions about how human genomes work.

“This is a gargantuan task,” J. Craig Venter, whose institute was not involved in Sc2.0, said in an interview. “Having a completely synthetic yeast would be a major milestone. I can’t say how impressed I am with what they’ve managed to pull off,” he said.

J. Craig Venter

Making a synthetic genome is not as simple as creating a carbon copy of what nature has already produced. The project is partly motivated by the belief that scientists can improve upon what nature has created.

“These synthetic yeast cells allow us to think about how the genome could have been organized,” Patrick Cai, a synthetic biologist at the University of Manchester, said in an email. “Our understanding of genomes is largely based on the observation of these natural genomes. The ability to build synthetic genomes will lead us to a much deeper understanding of the first principles of life.”

Patrick Cai

So far, the scientists have brought seven and a half synthetic chromosomes together under one Baker’s yeast cell, accounting for 54% of the organism’s DNA. That process of consolidation has proven trickier than expected, but scientists are already envisioning future uses for the completed cell.

“Baker’s yeast has always been the world’s number one microbe for making things for humans,” said Tom Ellis, a synthetic biologist at Imperial College London whose lab constructed one of the yeast chromosomes. “And with a finished synthetic cell, it opens up the possibility of making those products — biochemicals, drugs, antibodies, vaccines, biomaterials — in more optimal ways and with more diverse chemistry too.”

Decluttering and debugging a genome

Dreams of writing genomes, rather than just reading them, took hold at the turn of the century soon after scientists finished sequencing the first human genome. Researchers at Venter’s institute “booted up” the first bacteria with a synthetic genome in 2010 and refined and minimized its code in subsequent years.

Tom Ellis

For Boeke, creating a synthetic yeast genome was the natural next step. Yet, as simple as a yeast cell is compared to a human, its genome is still much larger than that of bacteria. It took about eight years before the first synthetic yeast chromosome was finished in 2014. In the years since, with the help of labs around the world and armies of undergrads, the Sc2.0 consortium has finally finished constructing the chromosomes.

One of the surprises that the group faced was that while the yeast was often healthy with one synthetic chromosome, the cells sometimes got sick when multiple synthetic chromosomes were added, sending the scientists back to the drawing board to figure out what went wrong and debug the design.

“It indicates that there are more mysteries within the genomic sequences than we thought,” said Junbiao Dai, deputy director of the Shenzhen Institute of Synthetic Biology, whose lab made one of the chromosomes. “Debugging is a really big time-consuming process.”

Junbiao Dai

 The Sc2.0 project shows that “you have to build it to understand it,” Venter said. “Every time we or somebody else tries to make something, we find out that there are huge gaps in our knowledge.”

The synthetic yeast genome has thousands of changes, reducing its length by about 10% compared to a natural genome, Boeke said. Some of those changes include stripping out repetitive DNA sequences that the scientists believe have accumulated over time and are unnecessary. So far, removing ones called transposons hasn’t had a negative effect on the cells.

The team also did some reorganizing. Hundreds of genes encoding tRNA molecules — which are crucial for protein production — are normally scattered across the yeast’s chromosomes. Cai’s lab took those genes and put them all together on a synthetic tRNA neochromosome.

Repetitive regions and tRNA genes are both hotspots for genetic mishaps that damage DNA. While clumping the tRNA genes together “could really create a nightmare,” some additional tinkering to reduce their liabilities seems to have worked, Boeke said. “We’re seeing if we can build a more stable genome than the natural genome.”

Jay Keasling

They also installed tidbits of DNA throughout the genome that they can use to easily add, remove, or rearrange genes. That technique, called Scramble, allows scientists to rapidly generate thousands to millions of genetic variants of yeast. Boeke compares the approach to shuffling a massive deck of cards, each representing a gene, over and over.

“One of those hands is going to give you a royal flush, the best possible hand in poker. And another one’s going to give you the best hand in gin rummy,” Boeke said, with different “winning hands” for researchers making antibodies, biofuels, or vaccine antigens. “It’s going to be a very practical tool for biotech companies that are trying to optimize yeast to produce useful products.”

“It’s such a cool project, and coordinating all these institutions and investigators is a herculean task,” said Jay Keasling, a bioengineer at the University of California, Berkeley, who was not involved in the effort. “It’s a stepping stone to what comes next, and just like DNA sequencing got cheaper and cheaper, doing this will get easier and easier.”

Designer genomes for making drugs

Scientists are already envisioning a new project, Sc3.0, to dramatically shrink the size of the yeast genome, only retaining genes that are absolutely vital to life.

“Imagine stripping back your smartphone to the most basic functions and having everything else as an optional app — its battery life would probably be a lot better. We’d like to try to do that for cells,” Ellis said.

Shen Yue

Shen Yue, chief scientist of synthetic biology at BGI-Research in China, is excited to expand the genetic code of the synthetic yeast, allowing the cells to incorporate new amino acids beyond the standard twenty building blocks used to make peptides and proteins. Those new amino acids could grant new footholds for making antibody-drug conjugates, she said, or creating protein therapies with improved properties, like less frequent dosing.

Sc2.0 was once viewed as a stepping stone towards creating a fully synthetic human genome. Boeke was previously among the leaders of a grassroots effort called Human Genome Project-Write, announced in 2016. Yet, without concerted funding, the goal of synthesizing a human genome remains far off.

“The human genome is 200 times larger, not to mention a lot more complicated and difficult to work with,” Boeke said. “It’s just not practical.”

Boeke said he withdrew from the group during the pandemic because his lab was busy helping with Covid-19 testing for New York City. But he also thinks that the time it would take to synthesize a full human genome poses a challenge. The cost of synthesizing DNA is another barrier.

Joel Bader

“I’m surprised that the cost of the raw starting materials hasn’t come down more,” said Joel Bader, professor of biomedical engineering at Johns Hopkins University who was part of Sc2.0.

Several biotech companies are working on new methods for making DNA in the lab cheaper and faster. It’s too soon to say if they will succeed, but the value of making fully synthetic genomes could soon be put to the test when the synthetic yeast is complete. “When all of those chromosomes are consolidated, that’s when the power of Sc2.0 is really going to take off,” Boeke said.

“I have a bet on a case of very good wine with a colleague who thinks we won’t be able to do it,” he said. “But I’m pretty confident I’m going to be drinking some good wine.”

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Angry Shouting Aside, Here’s What Biden Is Running On

Angry Shouting Aside, Here’s What Biden Is Running On

Last night, Joe Biden gave an extremely dark, threatening, angry State of the Union…



Angry Shouting Aside, Here's What Biden Is Running On

Last night, Joe Biden gave an extremely dark, threatening, angry State of the Union address - in which he insisted that the American economy is doing better than ever, blamed inflation on 'corporate greed,' and warned that Donald Trump poses an existential threat to the republic.

But in between the angry rhetoric, he also laid out his 2024 election platform - for which additional details will be released on March 11, when the White House sends its proposed budget to Congress.

To that end, Goldman Sachs' Alec Phillips and Tim Krupa have summarized the key points:


While railing against billionaires (nothing new there), Biden repeated the claim that anyone making under $400,000 per year won't see an increase in their taxes.  He also proposed a 21% corporate minimum tax, up from 15% on book income outlined in the Inflation Reduction Act (IRA), as well as raising the corporate tax rate from 21% to 28% (which would promptly be passed along to consumers in the form of more inflation). Goldman notes that "Congress is unlikely to consider any of these proposals this year, they would only come into play in a second Biden term, if Democrats also won House and Senate majorities."

Biden also called on Congress to restore the pandemic-era child tax credit.


Instead of simply passing a slew of border security Executive Orders like the Trump ones he shredded on day one, Biden repeated the lie that Congress 'needs to act' before he can (translation: send money to Ukraine or the US border will continue to be a sieve).

As immigration comes into even greater focus heading into the election, we continue to expect the Administration to tighten policy (e.g., immigration has surged 20pp the last 7 months to first place with 28% in Gallup’s “most important problem” survey). As such, we estimate the foreign-born contribution to monthly labor force growth will moderate from 110k/month in 2023 to around 70-90k/month in 2024. -GS


Biden, with House Speaker Mike Johnson doing his best impression of a bobble-head, urged Congress to pass additional assistance for Ukraine based entirely on the premise that Russia 'won't stop' there (and would what, trigger article 5 and WW3 no matter what?), despite the fact that Putin explicitly told Tucker Carlson he has no further ambitions, and in fact seeks a settlement.

As Goldman estimates, "While there is still a clear chance that such a deal could come together, for now there is no clear path forward for Ukraine aid in Congress."


Biden, forgetting about all the aggressive tariffs, suggested that Trump had been soft on China, and that he will stand up "against China's unfair economic practices" and "for peace and stability across the Taiwan Strait."


Lastly, Biden proposed to expand drug price negotiations to 50 additional drugs each year (an increase from 20 outlined in the IRA), which Goldman said would likely require bipartisan support "even if Democrats controlled Congress and the White House," as such policies would likely be ineligible for the budget "reconciliation" process which has been used in previous years to pass the IRA and other major fiscal party when Congressional margins are just too thin.

So there you have it. With no actual accomplishments to speak of, Biden can only attack Trump, lie, and make empty promises.

Tyler Durden Fri, 03/08/2024 - 18:00

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United Airlines adds new flights to faraway destinations

The airline said that it has been working hard to "find hidden gem destinations."



Since countries started opening up after the pandemic in 2021 and 2022, airlines have been seeing demand soar not just for major global cities and popular routes but also for farther-away destinations.

Numerous reports, including a recent TripAdvisor survey of trending destinations, showed that there has been a rise in U.S. traveler interest in Asian countries such as Japan, South Korea and Vietnam as well as growing tourism traction in off-the-beaten-path European countries such as Slovenia, Estonia and Montenegro.

Related: 'No more flying for you': Travel agency sounds alarm over risk of 'carbon passports'

As a result, airlines have been looking at their networks to include more faraway destinations as well as smaller cities that are growing increasingly popular with tourists and may not be served by their competitors.

The Philippines has been popular among tourists in recent years.


United brings back more routes, says it is committed to 'finding hidden gems'

This week, United Airlines  (UAL)  announced that it will be launching a new route from Newark Liberty International Airport (EWR) to Morocco's Marrakesh. While it is only the country's fourth-largest city, Marrakesh is a particularly popular place for tourists to seek out the sights and experiences that many associate with the country — colorful souks, gardens with ornate architecture and mosques from the Moorish period.

More Travel:

"We have consistently been ahead of the curve in finding hidden gem destinations for our customers to explore and remain committed to providing the most unique slate of travel options for their adventures abroad," United's SVP of Global Network Planning Patrick Quayle, said in a press statement.

The new route will launch on Oct. 24 and take place three times a week on a Boeing 767-300ER  (BA)  plane that is equipped with 46 Polaris business class and 22 Premium Plus seats. The plane choice was a way to reach a luxury customer customer looking to start their holiday in Marrakesh in the plane.

Along with the new Morocco route, United is also launching a flight between Houston (IAH) and Colombia's Medellín on Oct. 27 as well as a route between Tokyo and Cebu in the Philippines on July 31 — the latter is known as a "fifth freedom" flight in which the airline flies to the larger hub from the mainland U.S. and then goes on to smaller Asian city popular with tourists after some travelers get off (and others get on) in Tokyo.

United's network expansion includes new 'fifth freedom' flight

In the fall of 2023, United became the first U.S. airline to fly to the Philippines with a new Manila-San Francisco flight. It has expanded its service to Asia from different U.S. cities earlier last year. Cebu has been on its radar amid growing tourist interest in the region known for marine parks, rainforests and Spanish-style architecture.

With the summer coming up, United also announced that it plans to run its current flights to Hong Kong, Seoul, and Portugal's Porto more frequently at different points of the week and reach four weekly flights between Los Angeles and Shanghai by August 29.

"This is your normal, exciting network planning team back in action," Quayle told travel website The Points Guy of the airline's plans for the new routes.

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Walmart launches clever answer to Target’s new membership program

The retail superstore is adding a new feature to its Walmart+ plan — and customers will be happy.



It's just been a few days since Target  (TGT)  launched its new Target Circle 360 paid membership plan. 

The plan offers free and fast shipping on many products to customers, initially for $49 a year and then $99 after the initial promotional signup period. It promises to be a success, since many Target customers are loyal to the brand and will go out of their way to shop at one instead of at its two larger peers, Walmart and Amazon.

Related: Walmart makes a major price cut that will delight customers

And stop us if this sounds familiar: Target will rely on its more than 2,000 stores to act as fulfillment hubs. 

This model is a proven winner; Walmart also uses its more than 4,600 stores as fulfillment and shipping locations to get orders to customers as soon as possible.

Sometimes, this means shipping goods from the nearest warehouse. But if a desired product is in-store and closer to a customer, it reduces miles on the road and delivery time. It's a kind of logistical magic that makes any efficiency lover's (or retail nerd's) heart go pitter patter. 

Walmart rolls out answer to Target's new membership tier

Walmart has certainly had more time than Target to develop and work out the kinks in Walmart+. It first launched the paid membership in 2020 during the height of the pandemic, when many shoppers sheltered at home but still required many staples they might ordinarily pick up at a Walmart, like cleaning supplies, personal-care products, pantry goods and, of course, toilet paper. 

It also undercut Amazon  (AMZN)  Prime, which costs customers $139 a year for free and fast shipping (plus several other benefits including access to its streaming service, Amazon Prime Video). 

Walmart+ costs $98 a year, which also gets you free and speedy delivery, plus access to a Paramount+ streaming subscription, fuel savings, and more. 

An employee at a Merida, Mexico, Walmart. (Photo by Jeffrey Greenberg/Universal Images Group via Getty Images)

Jeff Greenberg/Getty Images

If that's not enough to tempt you, however, Walmart+ just added a new benefit to its membership program, ostensibly to compete directly with something Target now has: ultrafast delivery. 

Target Circle 360 particularly attracts customers with free same-day delivery for select orders over $35 and as little as one-hour delivery on select items. Target executes this through its Shipt subsidiary.

We've seen this lightning-fast delivery speed only in snippets from Amazon, the king of delivery efficiency. Who better to take on Target, though, than Walmart, which is using a similar store-as-fulfillment-center model? 

"Walmart is stepping up to save our customers even more time with our latest delivery offering: Express On-Demand Early Morning Delivery," Walmart said in a statement, just a day after Target Circle 360 launched. "Starting at 6 a.m., earlier than ever before, customers can enjoy the convenience of On-Demand delivery."

Walmart  (WMT)  clearly sees consumers' desire for near-instant delivery, which obviously saves time and trips to the store. Rather than waiting a day for your order to show up, it might be on your doorstep when you wake up. 

Consumers also tend to spend more money when they shop online, and they remain stickier as paying annual members. So, to a growing number of retail giants, almost instant gratification like this seems like something worth striving for.

Related: Veteran fund manager picks favorite stocks for 2024

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