Tag Archives: synthetic


New bio-synthetic circuits can teach old cells new tricks — such as killing cancer

New research at Caltech paves the way for programmable cells.


Image via Pixabay.

The research team has developed a biological toolkit of proteins which can be mixed and matched to create circuits that program new behaviors into cells. As a proof-of-concept, the team designed and built such a circuit and added it to human cells growing in culture in the lab. The mechanism is meant to detect the activation of a certain cancer-causing gene — in which case it causes the cell to self-destruct.


One goal of synthetic biology is to enable living cells to learn new tricks, ranging from relatively simple ones, such as emitting light in certain conditions, to the more complex — for example, detecting and responding to disease. The most common way of doing this is by altering a cell’s genome. However, such alterations are permanent and will be passed on by the cell to its daughters, which is undesirable in several applications.

So, a lot of effort has been spent in synthetic biology laboratories across the world to develop less-permanent solutions, says Michael Elowitz, coauthor of the new paper, a professor of biology and biological engineering, and a Howard Hughes Medical Institute investigator. Such changes should be removable, he adds, or last only a certain time; they would be administered, carry out their intended function, then allow the cell to revert to its original state. Ideally, they should also be highly targeted: instead of affecting all cells indiscriminately, they could detect when something goes wrong on the cellular level and fix it accordingly.

Led by postdoctoral fellow Xiaojing Gao and graduate student Lucy Chong, the Caltech team developed a set of protein building blocks that they hope will enable synthetic biology to shift its paradigm towards these temporary changes.

The proteins can be assembled in various combinations to produce biological circuits that can sense their environments and act if required. Just like electronic transistors can be linked to create the huge range of circuits today, the proteins can form systems that handle everything from signal processing to logical computation.

“One of the biggest challenges in biomedicine is specificity: How do you make a therapeutic that will affect only a particular type of cell? Then, how do you respond by modifying that cell in a very specific way?” says Elowitz.

“These tasks are challenging for drugs, but biological circuits could excel at them. Protein circuits can be programmed to sense many types of information, process it, and respond in different ways. In fact, the reason our cells usually work as well as they do is the incredible power of our natural biological circuitry.”

To prove that their approach works, the team constructed a biological circuit that can detect whether cells in a culture bear a cancerous gene and if so, destroy them. This circuit remained inactive when presented with healthy cells.

“This work is simply a proof of principle and we haven’t demonstrated these functions in animals yet,” Gao adds. “However, this framework could help us transition to using programmable, cell-based therapies as medicines.”

The work was enabled by the team’s efforts to engineer proteins that regulate (interact with) one another in similar ways, allowing them to act as interchangeable building blocks in the same mechanism.

The paper “Programmable protein circuits in living cells” has been published in the journal Science.

This startup plans to end rhino poaching by counterfeiting illegal goods — and it could work

A Seattle-based startup plans to save the rhinos — by outselling the poachers. Key to this strategy will be bio-fabricating fake horns out of keratin, the substance hair and fingernails are made of, to tank the price of horns on the black market and drive poachers out of business.

Black rhino horn.

Image via Wikimedia.

There’s one pretty nifty concept in economics that has stubbornly defied policy ever since someone first thought of banning anything — supply and demand. It’s why the Prohibition worked about as well as a raft made of concrete and why the harder we push forth the “war on drugs” the less headway we make.

By eliminating any legal avenue of satisfying a certain demand, bans effectively grant a monopoly over that good or service to the black market. In the process, officials lose any control over said commodity. Prices soar because that’s how monopolies work. The extra value justifies the risk of selling a ‘banned’ good, supply grows to meet demand, and voila! It’s illegal, but it’s lucrative, so trade flourishes. To put it bluntly, when people want something, the fact that it’s “illegal” won’t stop them. They’ll just go buy it (at a premium) from a shady dude in a shady alley instead of a supermarket.

That same economic ebb-and-flow is killing off the rhino today. The animals’ horns are banned for trade under international law and  have become ridiculously valuable on the black market, fetching up to US$60,000 a pound ($133,200 per kilogram). That’s about three to four times more than gold, depending on who you’re asking. Demand is powered chiefly by East Asian markets, with Vietnam and China making up the bulk of trade. Horns are used to make high-valued carvings, from cups to jewelry, and traditional Chinese medicine holds that they will make you, among other things, quite horny. A pun I’d delight over if not for the tragedy of the situation.

The end of the matter is that rhinos today are on the brink of extinction. Decades of Western trophy hunting, poaching, and habitat destruction have decimated overall rhino populations. Between 1970 and 1992, for example, black rhinos (Diceros bicornis) saw a 96% reduction in numbers. Other species are also hard pressed, such as the Javan rhino (Rhinoceros sondaicus), currently estimated to number only 60 individuals according to the World Wildlife Foundation, or the white rhinos (Ceratotherium simum) that are still making a comeback from numbering only 6 individuals in 2014.

Rhino sizes.

Size comparison for the five species of rhino.
Image via Wikimedia.

Three out of the five rhino species are listed as Critically Endangered on the IUCN’s Red List, and not a single one listed above “Vulnerable”. Habitat loss and poaching are currently the biggest threats to the rhinos. According to nonprofit Save the Rhino, 1,054 rhinos were killed in 2016 in South Africa alone, up from just 13 animals in 2007.

Pss, kids, wanna buy some horns?

Enter Seattle-based biotech startup Pembient. They’re trying to solve half the rhinos’ problems by literally making rhino horns so dirt-cheap no poacher worth his salt will bother with them. Their idea is to bio-fabricate fake horns out of keratin, a protein organisms use when strength and flexibility are required. It makes up stuff like fingernails and hooves, hair or fur, horns, and claws. By 3D printing keratin, Pembient hopes to manufacture fake horns that are identical on a “macroscopic, microscopic, and molecular” level to the real ones, according to its CEO and co-founder Matthew Markus.

The scheme isn’t ready to go right now. Once the fabricated horns are up to scratch and market-ready, however, they’ll feel so real that it will be “impossible” to distinguish them from natural horns, Markus told Business Insider. They’ll then be injected into the Asian carvers’ supply chain through various sources masquerading as honest poachers trying to get by. In the end, nobody will know whether they’re buying real or fake.

“Trust me, it’s the real deal. Fresh out of the savanna.”
Image credits Fathromi Ramdlon.

In effect, Pembient plans to flood illegal markets with super-cheap, rhino-friendly, counterfeit horns. Because they’re manufactured in bulk in a plant, the fakes will be much cheaper and could be sold for significantly less than the real horns. Over time, since people won’t be able to tell the two apart, this unfair competition will bring prices down, sending poachers looking for new employment.

“If you cordon rhino horn off, you create this prohibition mindset,” Markus said. “And that engenders crime, corruption, and everything else that comes with a black market.”

It’s an interesting strategy, and radically different from traditional approaches used by conservationists. Bringing down demand for horns isn’t feasible, Markus thinks, adding that “it’s not really ethical either.” Instead, Pembient plans to increase supply so much that it would be impossible to turn a profit from poaching rhinos.

“These practices are based on thousands of years of cultural tradition — they’re a lot older than Thanksgiving,” he added, reffering to the traditional practices that maintain the rhino horn trade.

“We can’t just tell them to stop.”

There are some concerns leveled at the startup, however. In particular, International Rhino Foundation and Save The Rhino International, two NGOs working on rhino conservation, have raised concerns regarding the plans’ efficacy, pointing out that the black market is already swamped in fake horns and prices are still incredibly high.

“More than 90% of ‘rhino horns’ in circulation are fake (mostly carved from buffalo horn or wood), but poaching rates continue to rise annually,” the organizations wrote in a joint statement.

The two also argued that synthetic horns will divert attention from the “real problem,” which is to end rhino poaching.

Still, rhinos are running out of time as well as numbers, and as we’ve seen earlier, poaching has picked up in recent years. Markus agrees that Pembient’s approach is fundamentally different than current conservation efforts, but thinks his approach could help finally end poaching for good.

Personally, I’d like to think that while people may want the horns, nobody explicitly wants to kill rhinos. Tradition is a central pillar of many people’s lives, but I’d advocate for compromise. After all, traditionally, most people would work in the field and eek out a pretty bleak livelihood before an untimely end at the hands of dysentery some other, equally-jolly way to die horribly. A state of affairs which, I’m sure we can all agree, is best left in the past. So I’d really like to see Pembient succeed at their goal — for “restore-faith-in-humanity” points, if nothing else.

A “prevention and treatment” approach has shown efficacy in addressing drug abuse, so it might work for rhino horn trade as well. Time will tell. In August, the company introduced a novel cryptocurrency program, the “Pembicoin” to fund their research and development. Each coin will be redeemable for one gram of bio-fabricated rhino horn once they become available, in 2022, according to the company’s website.

If Pembient’s approach proves efficient, it could pave the way for synthetic ivory to combat elephant poaching in the future.

Researchers complete 30% of the synthetic yeast chromosome — synthetic life is just around the corner

An international research effort to construct the first fully synthetic yeast is well under way. The scientists have fully designed the fungus’ genome and have already built five of its final sixteen chromosomes — planning to have the rest completed by the end of the year.

Image credits Paul / Pixabay.

Yeast has to be humanity’s favorite fungus. Sure, other shrooms taste better in a saute or make for a much more entertaining way to spend some free time, but yeast has been by our side since times immemorial. Whenever we’ve needed something fermented, yeast had our back. Without it, there would be no alcohol, no bread, no fish sauce!

Since modern industries need to ferment more stuff much faster and into a more varied range of end products than ever before (think biofuels, insulin, antibiotics, THC), scientists have spent the last two decades sequencing yeast genome to produce different strains useful for all these products. That still leaves us limited by much of the yeast’s genome, however, which nature sadly didn’t design for industrial applications — but not for long.

Led by NYU Langone geneticist Jef Boeke, PhD, and a team of more than 200 authors, the Synthetic Yeast Project (Sc2.0) has designed a full genome for a functioning synthetic version of Baker’s yeast (S. cerevisiae). The latest issue of seven papers coming from the group shows that they’ve successfully constructed almost one third of this genome — 5 out of 16 chromosomes. They plan to have the rest ready by the end of the year. The new round of papers consists of an overview paper and five individual ones describing the first assembly of synthetic yeast chromosomes synII, synV, synVI, synX, and synXII. A seventh paper provides a first look at the 3D structures of synthetic chromosomes in the cell nucleus.

“This work sets the stage for completion of designer, synthetic genomes to address unmet needs in medicine and industry,” says Boeke, director of NYU Langone’s Institute for Systems Genetics.

“Beyond any one application, the papers confirm that newly created systems and software can answer basic questions about the nature of genetic machinery by reprogramming chromosomes in living cells.”

Learning the A’s and C’s

Apart from the immediate utility of having a tailorable yeast strain to apply in industry, Baker’s yeast was selected because of it’s relative simplicity and similarity to human cells. Sc2.0’s researchers are akin to a group of genetic programmers — they add or remove parts of DNA from chromosomes to dictate new function or prevent diseases or weakness to various factors. It makes sense to start with a simple ‘program’ until you learn the basics, which you can then apply to more complex systems.

Three years ago, Sc2.0 successfully assembled the first synthetic chromosome (chromosome 3 or synIII) out of 272,871 base pairs — the blocks which make up DNA. This process starts with the researchers screening libraries of yeast strains to find which genes are most likely to have useful features. Then, they planning thousands of permutations in the genome in a process somewhat similar to very rapid evolution. Some of these changes introduce the new genes to make the yeast exhibit desired features, others remove bits of DNA which were shown not to have a function in past trials.

Stained polytene chromosomes.
Image credits Doc. RNDr. Josef Reischig, CSc.

After the computer models are finished, the team starts assembling the edited DNA sequence bit by bit until they have the whole thing. The completed sequences are then introduced into yeast cells, which handle synthesizing and finish building the chromosomes — the latest round of papers describes a major innovation in this last step.

Until now, the researchers had to finish building once piece of a chromosome before work could begin on the latter, severely limiting their speed. These sequential requirements bottle-necked the process and increased cost, Boeke said. So the team made efforts to “parallelize” chromosome assembly, with different labs around the world synthesizing different bits in strains which were then mated. The resulting yeast strains would in some instances have even more than one fully synthetic chromosome. A paper led by Leslie Mitchell, PhD, a post-doctoral fellow from Boeke’s lab at NYU Langone, described the construction of a strain containing three synthetic chromosomes.

“Steps can be accomplished at the same time in many locales and then assembled at the end, like networking laptops to create a global super computer,” says Mitchell.

Another paper describes how a team at Tsinghua University used the same parallelized method to synthesize chromosome synXII, which formed a molecule with more than a million base pairs (one megabase) in length when fully assembled — the longest synthetic chromosome ever made by humans. It’s still only 1/3,000 the length of a human chromosome, but it’s closer than we’ve ever come before.

The researchers also found that they can edit some dramatic changes into the yeast genome without killing the cells. They survived even when the team moved whole sections of DNA from one chromosome to another, DNA swaps between yeast species, often with very little effects on the cells.

There’s a huge potential to synthetic yeast. Scientists could tailor their genome to produce anything we need from drugs, to food, new materials, almost anything — just from sugar and raw materials. It could fundamentally change how we think about a lot of industries, potentially churning the same products as factories and labs from a humble barrel.

But the work performed under the Sc2.0 project also revolutionizes how we know about genome building and synthetic life. Yeast is simple, but the end goal is to one day move on to tailor-made plants, maybe even to perfect the human genome. But we’re still a long way from that. Right now, the team will focus on getting their yeast’s final A’s, T’s, G’s, and C’s in place.


Synthetic wine can mimic classic vintages, for a fraction of the time and price

Ava Winery, a start-up based in San Francisco, wants to let you enjoy the best of wines for a fraction of their current cost. To this end, they’ll bypass the costly growing and fermentation processes; in fact, they won’t use grapes at all. Their wines will be synthetically produced, by combining aromatic compounds with ethanol.

Image via avawinery

Mardonn Chua and Alec Lee got the idea in 2015, while visiting a Napa Valley winery. They were shown the bottle of a historic wine for US wineries — a Chateau Montelena, the first Californian Chardonnay rated above its French contenders, at the Paris Wine Tasting of 1976.

“I was transfixed by this bottle displayed on the wall,” says Chua. “I could never afford a bottle like this, I could never enjoy it. That got me thinking.”

Chua started experimenting with ethanol and fruity flavor compounds such as ethyl hexanoate in an attempt to recreate the experience of a quality wine. His first attempts were anything but, Chua himself describing them as “monstrous.” After six months of research however, they now believe they have produced a synthetic wine that can rival a traditionally-produced Italian white Moscato d’Asti sparkling wine. They’re now working on a Dom Pérignon mimic, and will begin shipping of the initial batch of 499 bottles for US$ 50 each later this summer.

An issue of taste

Wine is a very complex chemical solution. It can contain upwards of one thousand different chemical compounds, all working together to give wine its unique flavor. And, even though people have been enjoying this drink since antiquity, we still don’t really know which of these components contribute the most to wine’s taste and finish. The sheer number of different substances and substance interactions makes pinpointing flavor-driving molecules a crucial, but daunting task — like tasting a needle out of a haystack.

The team used gas chromatography, mass spectrometery and other methods to analyze the chemical make-up of several types of wine, such as Chardonnay, champagne and Pinot Noir. They wanted to identify these molecules — such as esters ethyl isobutyrate and ethyl hexanoate — and each of their concentrations. Then, they mixed them into their mimic wine and had a professional sommelier test the results as they experimented with different proportions of these molecules. The result?

“We can turn water into wine in 15 minutes,” claims Ava Winery.

Making wine is a lengthy process; good vines take years to grow, then there’s harvesting, fermenting and aging. A start-up that claims it can cut the whole process down to less than what it takes to order a pizza is naturally going to get the attention of the wine-making industry. Tony Milanowski, a winemaking expert at Plumpton College in the UK, isn’t too convinced about Ava’s mimic wine. Fatty acids and certain esters, released during fermentation in a wine-soluble form, may be difficult to dissolve in a synthetic drink, he says.

Ava Wineries don’t have what you’d call a classic winery layout.
Image provided by Ava.

Alain Deloire, director of the National Wine and Grape Industry Centre at Charles Sturt University, Australia, argues that the natural origin of wine has a huge role to play on the quality of the resulting drink, and that customers look for this natural element when they buy wine.

“It’s nonsense, to be honest with you,” Deloire, who has worked for Champagne specialists Moët & Chandon, adds.

Chua and Lee don’t think this will reduce the quality of their product, however.

“The big secret here is that most compounds in wine have no perceptible impact on the flavor or the aroma,” says Lee.

And, cutting to the chase, Lee concludes:

“It’s absolutely going to be substantially cheaper.”

Ava wines are unlikely to be labeled as such, as there are strict rules governing which products can use the term “wine.” The EU only allows it for fermented juice of grapes, whereas in the US other fruits can be used. Although this could damage the allure of synthetic wine, French winemaker Julien Miquel thinks there might be some interest in recreations of classic vintages. c

“There would be some curiosity on how close they could get,” he says.