Tag Archives: enzyme

Scientists create an enzyme that breaks down plastic much faster than before

To say that plastic is a big problem is an understatement. Every corner of the Earth has been tainted with this pollution — we may not realize it, but we are even eating plastic. But scientists are not idling around.

A team of researchers has created enzymes that also eat plastic, but that’s actually a good thing. The enzymes degrade plastic six times faster than before and could soon be used for recycling or to tackle the global plastic crisis.

Project co-lead John McGeehan pictured in the laboratory. Credit Portsmouth University

A group of researchers that had previously re-engineered a plastic-eating enzyme named PETase have now combined it with a second enzyme to speed up the process even more.

This could have big implications for recycling polyethylene terephthalate (PET), which is the most common type of plastic used in single-use products, the team explains.

“When we linked the enzymes, rather unexpectedly, we got a dramatic increase in activity”, said Prof John McGeehan, co-author, in a statement. “This is a trajectory towards trying to make faster enzymes that are more industrially relevant. But it’s also one of those stories about learning from nature, and then bringing it into the lab.”

McGeehan and his team found evidence that the bacterium Ideonella sakaiensis produces two enzymes that can break plastic down. The bacteria had first been discovered by Japanese scientists in 2016 when examining plastic items found in wastewater samples. Since then, researchers have worked to re-engineer the bacteria enzymes as a way to break down plastic mass.

The first enzyme the bacteria produces, PETase, can eat through solid plastic surfaces. PET is a chemical compound made up of molecules all tied together to form a complex structure, but when PETase gets onto the material, it breaks it down into simpler structures, including terephthalate (or TPA), bis(2-hydroxyethyl) TPA (or BHET), and mono-(2-hydroxyethyl) terephthalate acid (or MHET). In other words, the normally-unbreakable plastic gets broken down by the enzyme.

Back in 2018, the researchers engineered a version of the PETase enzyme, but it was only 20% more effective at degrading plastic than natural processes. But now, they have also created the second enzyme that the bacteria produce, which is called MHETase. The bacteria break down MHET into simpler forms, TPA and ethylene glycol.

The researchers looked at how these two enzymes reacted with pieces of plastic film in a lab setting. They found that without PETase around, MHETase doesn’t have any effect on the material. But the way the two work in trandem is much more promising: the enzyme combination can break down the plastic at a rate six times faster than naturally-occurring processes.

While this could change the way the world gets rids of plastic waste, it’is just one aspect of the plastic crisis. Creating the material, made of petrochemicals, is extremely polluting and climate-warming. So while the enzymes could reduce plastic pollution, a more holistic approach and sustainable should also be considered. Simply put, it’s not just about breaking down the existing plastic — we should not make so much of it in the first place.

The study was published in the journal PNAS.

Newly-discovered enzyme cocktail paves the way towards infinitely recyclable plastic

The researchers who made the improved version of the plastic-eating PETase enzyme have now developed a new ‘cocktail’ that can break down plastic much faster.

Image credits Džoko Stach.

Half of the cocktail is made up of the previous enzyme, PETase. The other ingredient, MHETase, is an enzyme found in the same strain of bacteria from which PETase was isolated. Together, they can break down plastic six times faster than alone, the team explains.

The findings can help pave the way towards improved plastic recycling methods, the team explains, which would slash plastic pollution as well as the emissions from plastic production.

Plastic-B-gone

“It took a great deal of work on both sides of the Atlantic, but it was worth the effort—we were delighted to see that our new chimeric enzyme is up to three times faster than the naturally evolved separate enzymes, opening new avenues for further improvements.”

Arguably the best place to find plastic-consuming compounds is in colonies of bacteria living on a diet of plastic bottles. But it turns out that it’s also the best place to find such a compound again.

The team isolated MHETase from the same strain of bacteria that produced PETase. Put together, the two are much more efficient at clearing out plastics than apart.

PETase decomposes polyethylene terephthalate (PET), a very common plastic used among other things for bottles, into its chemical components. This opens up the way — at least in theory — to infinitely-recyclable plastics.

Plastic is so useful because, on a chemical level, it is incredibly stable. The other side of the coin is that this makes it virtually indestructible by biological activity and other natural processes in any meaningful timescale (it takes several hundreds of years for it to break down in the environment). It also makes plastic hard to reuse over multiple cycles, as the process of breaking and reforming its chemical bonds has a noticeable effect on its physical properties.

After PETase was first isolated, the team worked to engineer it in the lab to make it more effective. By the end, they made it around 20% faster in breaking down PET.

MHETase, they explain, works as the teammate of PETase in the wild. Put together, they’re twice as fast in breaking down PET. After tweaking it in the lab, the team improved the effectiveness of this cocktail threefold — meaning that it breaks down plastic six times faster than PETase alone. What the team did in the lab is to essentially link the two molecules together chemically, instead of having them as separate solutions. Because of this link, PETase always has a MHETase molecule on hand to boost its speed.

“Our first experiments showed that they did indeed work better together, so we decided to try to physically link them, like two Pac-men joined by a piece of string,” says Professor John McGeehan, Director of the Centre for Enzyme Innovation (CEI) at the University of Portsmouth.

The resulting MHETase-PETase molecule breaks down plastic to its constituent parts, allowing for it to be recycled endlessly. The team hopes that the findings can help decrease reliance on crude oil or natural gas for raw materials and that they will help lower the emissions and pollution caused by plastic production.

The work, however, isn’t done. The authors used the Diamond Light Source in Oxfordshire, the UK’s largest synchrotron, to study the atomic structure of MHETase-PETase. Armed with its 3D structure, they are now working on designing a synthetic molecule that would perform the same task but faster and more efficiently. If successful, we might be able to engineer bacteria, or design completely synthetic ones, to produce plastic-destroying enzymes to clean out landfills and the ocean.

The paper “Characterization and engineering of a two-enzyme system for plastics depolymerization,” has been published in the journal PNAS.

Scientists transform Type A blood to universal donor blood using enzyme treatment

Blood is a scarce commodity. Talk to almost every medical facility on the planet and you’ll hear the same thing: there’s a blood shortage, more donors are needed. To make matters even more complicated, you can’t just give any type of blood to anyone.

People generally have one of four blood types: A, B, AB, or O. The differences between these blood types are defined by some rather unusual sugar molecules that bond with red blood cells — antigens and various proteins float in the plasma and on red blood cells, defining a person’s blood type. This blood type is extremely important for transfusions. Have someone with type A molecules give blood to someone with type B and you may very well kill them: the immune system will attack the foreign blood.

So in the case of transfusions, researchers need to be careful to give the right type of blood.

But there’s a catch: type O doesn’t have these antigens, meaning you can give type O blood to anyone. This is the so-called universal donor blood type, and it’s extremely important for transfusions, especially in emergency cases where doctors might not have the time to figure out what’s the patient’s blood group.

Transforming other types of blood into O type isn’t a new idea — it’s been tried before. However, the techniques were either too inefficient or too expensive to be applied at a large scale. Stephen Withers, a chemical biologist at the University of British Columbia (UBC) in Vancouver, Canada, may have found a better solution.

The problem with transforming one blood type to another is generally approached through enzymes which strip the blood of its type-giving molecules. Withers looked for enzymes in the gut bacteria — some of which are well known to consume sugar molecules similar to the ones that give the blood type. So he took a stool sample and harvested DNA from it, hoping that among the harvested DNA he’d also find the genes encode the bacterial enzymes that digest mucins. He further isolated this DNA and then encoded it into the biological jack of all trades — the Escherichia Coli bacterium (a common ‘workhorse’ for genetic studies, often used to store DNA sequences from other organisms) to see whether the resulting bacterium would be capable of stripping off the required molecules.

Although the results didn’t look promising at first, the process did work out in the end. Two of the enzymes produced thusly worked excellently, turning type A blood into type O blood. The enzymes originally came from a gut bacterium called Flavonifractor plautii, a common member of the human gut microbiome, rarely isolated from clinical human specimens.

[Also Read: New kind of artificial blood made in the land of Dracula]

If the results are confirmed, it would be an important breakthrough. Type O and type A each make up about 30% of the total donated blood, meaning that the supply of type O blood could be doubled, addressing a ubiquitous shortage, making life significantly easier for doctors, and ultimately, saving a lot of lives. To make matters even better, only small amounts of enzymes are required for this, and the whole process is relatively cheap.

“I am optimistic that we have a very interesting candidate to adjust donated blood to a common type,” concludes Withers.

However, more research is required to be sure that all the type A-defining molecules have been removing, as well as to ensure that nothing else was inadvertently changed about the blood. Any unforeseen error can put patients’ lives at risk.

Of course, this wouldn’t eliminate the blood crisis the world is facing, nor will it reduce the need for blood donors. It only means that that existing donated blood is more versatile — which is, in itself, an amazing achievement.

No Smoking.

Lab-tailored enzyme shows promise as a new and powerful treatment against tobacco addiction

New research from the Scripps Institute may pave the way to more efficient — and more enjoyable — ways of weaning off of nicotine.

No Smoking.

Image via Pixabay.

Nicotine addiction is an immensely powerful force, one that makes smokers keep smoking despite the habit’s well-documented impact on health. It’s what gets people hooked, and what makes most of those who gave up smoking relapse. Current estimations point to 60% of those who try cigarettes ending up as daily smokers, about 75% of daily smokers relapsing after quitting. However, one new, lab-tailored enzyme could help us fight against nicotine addiction by breaking most of it down before reaching the brain.

The compound was, thus far, shown to be efficient in rat models.

Nic-No-Tine

“This is a very exciting approach because it can reduce nicotine dependence without inducing cravings and other severe withdrawal symptoms, and it works in the bloodstream, not the brain, so its side effects should be minimal,” says principal investigator Olivier George, Ph.D., associate professor at Scripps Research.

The enzyme the team tested is known as NicA2-J1, and it’s a variation of a natural compound produced by Pseudomonas putida — which, interestingly, is the first patented organism in the world. This compound has previously been shown to reduce nicotine levels in the blood of mice.

And there lies the crux of the researchers’ interest in the enzyme. It breaks down nicotine before it even reaches the brain, making it very attractive as a means of fighting nicotine dependence. However, the original enzyme didn’t scrub nicotine fast enough for such a treatment strategy to work. So George’s team started by tweaking the enzyme to make it more efficient, increase its staying time in the bloodstream, and add a few other pharmacological properties.

The next step was to treat nicotine-dependent rats with the tweaked enzyme. For the first stage of the experiments, rats spent 21 hours per day, for 12 days, in a chamber where they could press a lever to receive a shot of nicotine. The rats soon understood the system, and self-administered nicotine until they became addicted to the substance. After these 12 days, the rats were only allowed access to nicotine once every 48 hours.

The rats experienced obvious withdrawal symptoms between these windows of time. They started escalating their intake while nicotine was available — a hallmark of deepening addiction — in a psychological bid to reduce discomfort caused by withdrawal.

However, not all rats fared the same. Those treated with the highest doses of NicA2-J1 (10 mg/kg) continued to pull the lever for a shot of nicotine if given the chance, but had significantly lower blood-nicotine levels compared to the rest of the animals. They also exhibited less pronounced signs of nicotine withdrawal, such as such as susceptibility to pain and aggressiveness, compared to the control group. One of the most encouraging finds is that NicA2-J1 treatment didn’t instantly trigger withdrawal symptoms, which usually happens when nicotine is blocked in a highly-dependent animal — think of quitting ‘cold-turkey’, but much more abruptly.

“It’s as if they were smoking 20 cigarettes but receiving the nicotine dose of only one or two, so that made their withdrawal process much less severe,” says study first author Marsida Kallupi.

“[W]hat’s unique about this enzyme is that it removes enough nicotine to reduce the level of dependence, but leaves enough to keep the animals from going into severe withdrawal,” George adds.

One of the most insidious effects of nicotine dependence is the continuation of use despite its adverse consequences — short-term impairment of lung function and physical fitness, alongside the longer-term risks of cancers, heart disease, or stroke. In other words, the compound is so addictive that users are compelled to seek it out no matter the cost. NicA2-J1 could also help in this regard, the team writes. When each lever-press had a 30% chance of directing an electric shock to the rats’ feet, those treated with NicA2-J1 quickly reduced their lever presses; those in the control group did not.

To model how effective the enzyme would be at fighting relapses, the team took the rats off of nicotine for 10 days straight — any smoker here will shiver at the mere thought (yes, nicotine addiction is that bad). The team gave each rat an injection of nicotine after the 10 days to restart their desire for the drug, and then restored their access to the lever. Untreated rats responded in a rather predictable way: they pressed the lever as much as they could, as fast as they could. Rats treated with NicA2-J1, in contrast, used the lever more sparingly. The same effect was seen when the team triggered relapse in all the rats using a stress-inducing compound (which was meant to mimic the way stress can cause relapse in humans).

 

[panel style=”panel-info” title=”Nicotine Addiction” footer=””]Nicotine is an extremely hard habit to kick as it fosters both physical and psychological dependence, and users develop tolerance over time. It’s an extremely addictive compound, similar to heroin and cocaine. Discontinuation of use (after dependence sets in) is particularly nasty, involving both affective (mood-related) and somatic (body-related) withdrawal symptoms, ranging from anxiety and poor mood to tremors. Withdrawal effects peak in the first few days of discontinuation but can last for upwards of several weeks. Most people don’t make it past the first few days.

“The majority of smokers would like to stop smoking, and each year about half try to quit permanently. Yet, only about 6 percent of smokers are able to quit in a given year,” reports the National Institute on Drug Abuse (NIDA).[/panel]

Since nicotine is extremely addictive, it’s hard to give up; even worse, those that do manage this feat are very prone to relapse. That, in itself, isn’t necessarily a bad thing; as the team notes in the paper’s opening line, however, “[t]obacco use disorder is the leading cause of disease and preventable death worldwide” (which is very bad). The CDC also supports this statement. NicA2-J1 shows a lot of promise as a treatment to help smokers wean off of nicotine since it prevents the substance from reaching the brain in the first place, takes the edge off of withdrawal, and makes relapses less likely to happen. The team hopes to start clinical trials with human subjects soon — but first, they’ll work on making the enzyme even more effective.

The paper “An enzymatic approach reverses nicotine dependence, decreases compulsive-like intake, and prevents relapse” has been published in the journal Science Advances.

Nicotine.

Newly-devised molecule might help people quit smoking by blocking nicotine break-down

Drugs that can actually help to quit smoking may soon find their way to a pharmacy near you.

Nicotine.

Image credits Lydia / Flickr.

Researchers from the Washington State University (WSU) have synthesized over a dozen compounds that can help smokers curb their dependence on nicotine, a new paper reports. The compounds work by slowing down the rate at which nicotine is broken down in the body, which should help people reduce their consumption of tobacco — or kick the habit altogether.

Breaking down the breaker-downs

Nicotine, like most other drugs, triggers the release of dopamine and serotonin in the brain — two chemicals that make us feel good. However, from the body’s point of view, nicotine isn’t very nice, so it has to go. Our liver produces an enzyme — dubbed CYP2A6 — to break the compound down (or ‘metabolize’ it). This process, however, can have nasty side-effects. Patients who have developed a dependence on nicotine can experience withdrawal symptoms ranging from anxiety and irritability to tingling in their extremities as the substance is flushed out of their system.

The process of metabolization, coupled with our bodies’ tendency to develop tolerance to active substances such as nicotine, means that users tend to increase intake of substances such as nicotine over time.

However, the process of metabolization could also help us kick the habit altogether. In the mid-90s, researchers found that people who had fewer copies of the gene that encodes the CYP2A6 enzyme tend to smoke less and are less likely to become addicted to smoking. In a bid to artificially-induce these traits into people with normal levels of CYP2A6, the team designed dozens of molecules that can bind to the enzyme and limit its ability to process nicotine.

This is the feeling that the researchers are targeting, said Travis Denton, assistant professor of pharmaceutical sciences, lead author and a former tobacco chewer who has been working on solutions to nicotine dependence for 15 years.

“I quit cold turkey and I know how hard it is. Would this have helped? I believe so, because again, the people who want to quit, really want to quit,” says lead author Travis Denton, assistant professor of pharmaceutical sciences at the WSU.

“They just can’t because it’s too doggone hard. Imagine if you could take this pill and your jitters don’t come on as fast — it’s just super reinforcing to help you quit.”

Co-author Philip Lazarus, Boeing distinguished professor of pharmaceutical sciences, says that inhibiting CYP2A6 shouldn’t have any effect on your overall health.

“If we could specifically target this enzyme, people should be fine, and it will possibly help them stop smoking or at least decrease their amount of smoking.”

So far, the team has been able to test the substances and make sure they don’t interfere with other major enzymes in the body — 18 of their molecules passed the test. The next step is for the Food and Drug Administration to approve clinical trials of the compounds, to see exactly what effect each of these compounds would have on the human body.

Molecules smoking.

Some of the 18 molecules the team developed and tested and their interaction with CYP2A6.
Image credits Travis T. Denton et al., 2018, JoMC.

Should even one of these molecules prove effective, it could bring significant benefits to public health. Smoking is the leading cause of preventable death worldwide, causing an estimated 6 million deaths per year. Cigarette smoking causes nearly one in every five deaths in the United States.

The paper “Identification of the 4-Position of 3-Alkynyl and 3-Heteroaromatic Substituted Pyridine Methanamines as a Key Modification Site Eliciting Increased Potency and Enhanced Selectivity for Cytochrome P-450 2A6 Inhibition” has been published in the Journal of Medicinal Chemistry.

Researchers ‘accidentally improve’ a plastic-munching enzyme

Researchers have created an enzyme that can break down the pervasive kind of plastic which takes hundreds of years to degrade; they did it by accident.

Enzyme-PET-interaction.

Electron microscope image of enzyme degrading PET plastic.
Image credits Dennis Schroeder / NREL.

The team initially started their research intending to take a better look at the crystal structure of a recently-discovered enzyme, PETase. This substance has evolved naturally and is known to break down and digest polyethylene terephthalate (PET) plastics. However, sometime during our intrepid band’s quest for knowledge, ‘disaster’ struck — the team introduced an unwanted mutation to PETase, making it more efficient at munching plastics than the original.

‘I totally wanted to do that, haha!’

“Serendipity often plays a significant role in fundamental scientific research, and our discovery here is no exception,” says co-author John McGeehan, a professor of structural biology at the University of Portsmouth in the U.K.

PETase was first detected in the bacterium Ideonella sakaiensis. The critter made a home in the soil under a PET-recycling facility in Japan and employed this enzyme to dine on bits of plastic waste that got lodged in the ground. Researchers think PETase is a redesigned version of an ancient enzyme aimed at breaking down waxy coatings, which plants sometimes employ to defend their tissues. This made PETase doubly attractive as a research subject: first, to help us understand its evolutionary path, and secondly because it could help us fight our ever-growing problem of plastic waste.

During their research, the team inadvertently changed the enzyme’s structure — this, however, had the fortunate effect of making it more effective, the team notes.

PETase doesn’t work very fast, and definitely isn’t up to the task of munching our plastic waste. The accidentally-improved version is a tad more efficient, but it’s main advantage isn’t speed: it’s scope. Its tweaked structure allows it to attack and consume another type of plastic called polyethylene furandicarboxylate (PEF), “literally drilling holes through the […] sample, according to co-author Gregg Beckham, a senior engineer at the National Renewable Energy Laboratory (NREL).

Still, despite its bigger teeth and expanded menu, this PETase 2.0 is still facing a mammoth challenge. Estimates place the global amount of plastic waste at around 9 billion tons (8.3 billion metric tons) — half of which has been produced since 2004. The findings, however, suggest that we may be able to solve the global plastic problem by improving enzymes such as PETase in the lab. Further research on this particular enzyme and its lab-derived cousins could lead to even more efficient plastic munchers, the authors report.

“Given these results, it’s clear that significant potential remains for improving its activity further,” said study co-author Nicholas Rorrer, a postdoctoral researcher at NREL.

The paper “Characterization and engineering of a plastic-degrading aromatic polyesterase” has been published in the journal Proceedings of the National Academy of Sciences.

Genetic-scissor enzyme eliminates HIV completely in mice trials

A new gene-snipping enzyme was successful in removing strands of HIV genetic material in mice trials. If the enzyme can prove its reliability in human trials it might revolutionize how we fight the virus forever.

HIV is no longer the death sentence it once was.

Through modern antiretroviral therapy, the virus can be kept at bay and patients have a fighting chance against it. But antiretroviral treatments are more of a band-aid than a cure to HIV: they are expensive, increase drug resistance in patients and can lead to a host of adverse reactions. To top it all off, because the virus can stay hidden in reservoirs throughout the body, the disease can continue to progress if the treatment is discontinued.

HIV infected cell (virus in yellow.)
Image credits go to flikr used NIAID

A research team from Germany thinks that they have found the answer: they have created a substance that they hope will finally allow us to create an affordable and efficient treatment for the virus. Dubbed Brec1, the enzyme can cut strands of viral DNA out of infected cells’ genetic code and preventing more of the virus from spawning.

The team successfully tested Brec1 on mice and their results make them confident that their enzyme can be used in clinical practice. If Brec1 can be adapted to cut HIV’s genetic material out of a patient’s cells and leave everything else undisturbed, the technique would allow physicians to finally produce an effective cure for the virus.

Brec1 was obtained using a genetic engineering technique known as directed evolution, which mimics the natural evolution processes of proteins. In a way, this process can be likened to animal husbandry; starting with the genetic information for a particular gene, they subjected it to iterative rounds of mutation, selected the ones closest to what they needed, and then used those to restart the cycle of mutation.

This way they ended up with an enzyme programmed to recognize and cut DNA on either side of the virus’ characteristic genetic sequences — an impressive feat, considering that HIV often mutates, making its signature hard to determine. The researchers identified a well-conserved sequence in the viral genetic make-up and tested how well the enzyme could cut out that sequence in bacteria, HIV-positive patients and mice infected with the human form of HIV.

After a few tweaks, Brec1 was successful in removing the information and then patching up the strands of genetic material after removal of the sequence. Examined 21 weeks later, cells treated with the enzyme showed no signs of HIV.

There have been previous attempts to create something similar to Brec1. Previous gene-snipping enzymes such as CRISPR or TALENS were effective in clearing out viral genetic material but didn’t result in a reliable cure — they also had a nasty habit of making accidental cuts elsewhere in the genome.

The debate around these enzymes has shown us that people aren’t all that thrilled of methods that alter our DNA. It’s what makes us what we are, and people are wary of the consequences of altering it. Antiretroviral methods, for all their shortcomings, don’t make people nearly as nervous.

But if Brec1 proves to be reliable — even better, infallible — in human trials as it was in this study, it’s likely that it will come at the forefront in our search for an HIV cure.

Though there are a few more questions that the team doesn’t have an answer to yet — like what will the enzyme do in cells infected with more than one strand of HIV — they plan to test Brec1 in humans in the near future.

The full paper, titled “Directed evolution of a recombinase that excises the provirus of most HIV-1 primary isolates with high specificity” has been published online in the journal Nature and is available here.

Self assembling nano material brings us tangibly close to water-powered cars

Indiana University scientists have built a highly efficient bio-material that can serve as a catalyst for hydrogen production. This material takes us halfway towards the long sought-after “holy grail” of splitting water to make hydrogen and oxygen for fueling cheap and efficient cars that run on water.

Artist’s rendering of P22-Hyd, the new biomaterial created by encapsulating a hydrogen-producing enzyme within a virus shell.
Image via sciencedaily

The team started with an enzyme called hydrogenase that can extract pure hydrogen gas out of water. The substance broke down easily however, so they strengthened it by placing it inside the capsid (the protein shell) of a bacterial virus. The new material is now 150 times as efficient than the unaltered enzyme.

“Essentially, we’ve taken a virus’s ability to self-assemble myriad genetic building blocks and incorporated a very fragile and sensitive enzyme with the remarkable property of taking in protons and spitting out hydrogen gas,” said lead author Trevor Douglas, the Earl Blough Professor of Chemistry in the IU Bloomington College of Arts and Sciences’ Department of Chemistry.

“The end result is a virus-like particle that behaves the same as a highly sophisticated material that catalyzes the production of hydrogen.”

The hydrogenase was produced using genetic material harvested from the common bacteria Escherichia coli, namely the genes hyaA and hyaB. The enzyme was then inserted inside the protective capsid of a virus known as bacteriophage P22,using methods previously developed by IU scientists.

The resulting biomaterial, called “P22-Hyd,” is much more efficient and durable than the enzyme alone, and is obtained through fermentation process at room temperature. P22-Hyd is dirt cheap (fermentation is free) and more environmentally friendly than materials currently used for fuel cells. The authors compare it to platinum, the most commonly used hydrogen catalyst today.

“This material is comparable to platinum, except it’s truly renewable,” Douglas said.

“You don’t need to mine it; you can create it at room temperature on a massive scale using fermentation technology; it’s biodegradable. It’s a very green process to make a very high-end sustainable material.”

As a bonus, P22-Hyd both breaks the chemical bonds of water to create hydrogen and also works in reverse to recombine hydrogen and oxygen to generate power.

“The reaction runs both ways — it can be used either as a hydrogen production catalyst or as a fuel cell catalyst,” he added.

Out of three naturally ocuring forms of hydrogenase, the team chose to use nickel-iron (NiFe)-hydrogenase — the others being di-iron (FeFe)- and iron-only (Fe-only)-hydrogenase. This form was preferred due to its ability to easily integrate into biomaterials and tolerate exposure to oxygen.

Unaltered NiFe-hydrogenase is highly susceptible to destruction from chemicals in the environment and breaks down at room temperatures — a poor choice for fuel cells. Encapsulation allows it much greater chemical resistance and enables it to catalyze at temperatures exceeding “comfortable,” permitting its use in manufacturing and commercial products such as cars.

“[These shortcomings are] some of the key reasons enzymes haven’t previously lived up to their promise in technology,” Douglas added.

Another is their difficulty to produce.

“No one’s ever had a way to create a large enough amount of this hydrogenase despite its incredible potential for biofuel production. But now we’ve got a method to stabilize and produce high quantities of the material — and enormous increases in efficiency.”

Seung-Wuk Lee, professor of bioengineering at the University of California-Berkeley, whose work has been cited in a U.S. Congressional report on the use of viruses in manufacturing and unaffiliated with the study, applauds the team’s work, saying:

“Douglas’ group has been leading protein- or virus-based nanomaterial development for the last two decades. This is a new pioneering work to produce green and clean fuels to tackle the real-world energy problem that we face today and make an immediate impact in our life in the near future.”

Beyond the new study, Douglas and his colleagues continue to craft P22-Hyd into an ideal ingredient for hydrogen power by investigating ways to activate a catalytic reaction with sunlight, as opposed to introducing elections using laboratory methods.

“Incorporating this material into a solar-powered system is the next step,” Douglas concluded.

New enzyme could be used as an insulin alternative, to treat diabetes and obesity

University of Montreal Hospital Research Centre (CRCHUM) scientists have identified a new enzyme that could protect the body from toxic levels of intra-cell sugar. When there is too much sugar in the body it gets processed into glycerol-3-phosphate, a buildup of which can damage internal organs. The team behind the study proved that G3PP is able to extract excess sugar from cells.

Their discovery should lead to the development of therapeutics for obesity and type 2 diabetes.

Image via pixlr

“When glucose is abnormally elevated in the body, glucose-derived glycerol-3 phosphate reaches excessive levels in cells, and exaggerated glycerol 3 phosphate metabolism can damage various tissues,” said Marc Prentki, principal investigator at the CRCHUM and professor at the University of Montreal.

“We found that G3PP is able to breakdown a great proportion of this excess glycerol phosphate to glycerol and divert it outside the cell, thus protecting the insulin producing beta cells of pancreas and various organs from toxic effects of high glucose levels.”

Mammalian cells derive the bulk of their energy from oxidizing glucose and fatty acids. These substances govern many physiological processes, from insulin and glucose production, all the way to fat accumulation and nutrient metabolization. But a too large intake of glucose disrupts these processes and can lead to obesity, type 2 diabetes and cardiovascular diseases.

Beta cells in the pancreas respond to changes in blood sugar levels, cracking up or toning down on insulin — a hormone that controls glucose and fat utilization. Usually this keeps blood sugar levels stable and cells happy and well supplied with fuel. As glucose is being used in cells, glycerol-3-phosphate is formed, a molecule central to metabolism since it is needed for both energy production and fat formation.

But when these nutrients are found in excess, they can actually damage beta cells, inhibiting their function. Blood sugar levels remain unchecked, skyrocket, and damage the beta cells even further. This leads to a vicious circle, shutting down the body’s system of managing its fuel. G3PP however isn’t produced by beta cells, and the team hopes it can be used to regulate formation and storage of fat as well as production of glucose in the liver.

“By diverting glucose as glycerol, G3PP prevents excessive formation and storage of fat” says Dr Murthy Madiraju, a scientist at CRCHUM.

Dr Prentki added: ‘It is extremely rare since the 1960s that a novel enzyme is discovered at the heart of metabolism of nutrients in all mammalian tissues, and likely this enzyme will be incorporated in biochemistry textbooks.’

The research team is currently in the process of discovering ‘small molecule activators of G3PP’ to treat cardio-metabolic disorders. These drugs will form a new class of drugs, being unique in the way they operate inside the body.

The treatment will first have to be confirmed in several animal trials before drugs for human use can be developed.

“This is an interesting paper and to some extent unusual as new enzymes involved in metabolic control are rare,” said Professor Iain Broom, Director of the Centre for Obesity Research & Epidemiology, Robert Gordon University.

But we should take great care as we develop this class of drugs, he adds”

“Care should be taken, however, in reading too much into the possibilities for treatment of disease by focusing on such individual enzymes, especially as the evidence for this control mechanism comes from isolated cells.”

“This paper does have an important finding, however, and should not be dismissed lightly – but I would draw the line at statements of ‘guilt-free sugary treats’,” he said, referring to the media’s take on the story. ”

This is not an accurate by-line for this interesting piece of science.”

The paper can be found online in the journal Proceedings of the National Academy of Sciences.

 

gm_arctic_Apples

Genetically modified apples don’t turn brown when sliced or bruised

The US government approved a genetically modified apple that doesn’t turn brown when bruised or sliced. While most genetic alterations of plants involve making these more resilient to pests or yield more, the non-browning apples were made out of cosmetic considerations. Of course, the apples will still  rot and eventually get brown, but in time and not so easily when stressed (cell rupture). But despite the government approval, voices run rampant against the genetically modified fruit from behalf of anti-GMO groups, as well as rivaling food companies.

These apples keep their colour

gm_arctic_Apples

Left, a normal sliced apple left to oxidize; right, genetically modified Arctic apples. Image: Okanagan Specialty Fruits

Okanagan Specialty Fruits, a rather small Canadian company, is behind the new product. An oddity in itself considering the GM space is dominated by giants like Monsanto and DuPont Pioneer. Their intention is to address both consumer and food companies who might benefit from apples that don’t turn brown, which hardly sell in super markets. During harvest and shipping, tons and tons of apples get bruised, turn brown and end up in the gutter. As reported earlier, so-called ugly fruit and veggies get thrown away at a massive scale just because they don’t appeal to the market’s aesthetic standards – between 20 and 40 percent of all fresh food is thus thrown away by farmers. Companies that process apples, like sliced apples, may also greatly benefit. It’s believed that 30% of the cost for sliced apples goes into tainting these with anti-oxidants so they don’t go brown, so consumers will get to buy these 30% cheaper.

When you cut an apple in half – or a banana or potato for that matter – you’ll notice it starts getting brown within a couple of minutes. This is caused by the reaction between an enzyme found in the apples, as well as in other foods, called  polyphenol oxidase or tyrosinase with oxygen and  iron-containing phenols. The fruit starts to oxidize, when electrons are lost to another molecule (in this case the air), and the food turns brown. Basically, an edible rusty crust is formed on your food. You see the browning when the fruit is cut or bruised because these actions damage the cells in the fruit, allowing oxygen in the air to react with the enzyme and other chemicals. To keep your sliced apples as fresh as possible, you need to reduce the amount of oxygen that gets to react with the tyrosinase. Putting the apples under water or vacuum packing are just a few effective ways to do this, but you can also try adding lemon juice (acidic) to reduce the pH of the exposed surface. Or, you can buy Okanagan’s apples and be done with it.

To fix the oxidation problem, the Okanagan researchers engineered their apples – called Arctic apples – so these make less of the polyphenol oxidase. What’s interesting though is that rather than snipping out the genetic code responsible for producing the enzyme, the researchers actually added more copies of the enzyme’s gene, causing the fruit to switch off the whole lot.

Neal Carter, the president of Okanagan, said the apple had “a lot of silent supporters” and would be popular with the food service business.

“I can’t believe how many requests we’ve had just this morning to our website from people who want to buy trees,” he said.

Already, one grower is allegedly planting  20,000 trees this spring, which should yield 5,000 to 10,000 pounds of apples by the fall of 2016, that’s if nothing happens in the meantime. A lot of people are critical of the Arctic apples, which come in two varieties, Granny Smith and Golden Delicious.

“This G.M.O. apple is simply unnecessary,” Wenonah Hauter, executive director of Food & Water Watch, said in a statement, using the initials for “genetically modified organism.” “Apple browning is a small cosmetic issue that consumers and the industry have dealt with successfully for generations.”

Carter argues, however, that his apples aren’t technically genetically modified organisms, not in the traditional sense at least. In the lab, plants are typically altered by adding a gene from some foreign organism, but Carter’s apples were made by internal tweaking of its genes – there’s nothing “alien” inside. But consumer groups say shutting off the browning mechanism could have unintended effects. The Agriculture Department, however, said the Arctic apples seemed to be nutritionally equivalent to other apples. In November, the Agriculture Department approved a genetically engineered potato developed by the J.R. Simplot Company that uses a similar technique to prevent browning.

 

alcohol to CO2

New process turns CO2 into alcohol using enzymes

We’ve previously told you how our ancestors’ adaptation to metabolizing alcohol which first happened some 10 million years ago may have been essential to their survival. There’s more to it though. The same enzyme that metabolizes alcohol, dehydrogenase (ADH4), may be eventually used to transform CO2 into alcohol, which could be later used as a fuel, according to a paper recently presented at a conference by researchers at Johannes Kepler University, Austria.

A shot of CO2

alcohol to CO2

Image credit: cbhic.com

In the wake of the recent climate change talks in Lima, where environmental ministers from each United Nations state met to discuss a global warming mitigation framework, there’s a lot of talk now about what countries can do to limit their CO2 emissions. Arguably, there’s a great deal of damage that’s already been made. Even if the world stopped dumping CO2 into the atmosphere today, there’s still a net negative CO2 imbalance that’s set to stay this way for centuries. Thus, the idea is to find ways to sequestrate or transform CO2 from the atmosphere or oceans. The approach suggested by the Austrian researchers might turn out to be viable.

The dehydrogenase enzyme is employed inside the liver to breakdown alcohol into a series of byproducts, including carbon dioxide. Being a reversible reaction, scientists found that it could prove to be useful into turning CO2 back into alcohols such as methanol or butanol.

The team developed a three-step process, with each step employing a different enzyme to break down the CO2 first into acids, then to aldehydes and finally to alcohols. In greater detail, dehydrogenase was mixed into a alginic acid solution and silicates, which gelled into beads. These were mixed in a buffer solution where nicotinamide adenine dinucleotide hydrogenase (NADH) was added – another enzyme that generates hydrogen and electrons to power the reaction. Finally CO2 was pumped through the mixture.

There’s one big problem with this process, though: it’s highly inefficient. That’s because the NADH is extremely expensive and, most importantly, it gets oxidized really fast. To make the enzyme work again, a lot of energy needs to be pumped into the system or a lot more than the environmental benefit gained from transforming the CO2 in the first place. So the enzyme was shelves in favor of an elecrochemical method. Instead of NADH, an electrode made out of carbon fiber felt was used. When in contact with the beads mixture, the felt acted like a sponge concentrating the beads thus turning the electrode into an enzyme coated one. When electricity is ran through the system, complex alcohol molecules such as ethanol and butanol are generated by a repeatable process.

Of course, if these alcohols are used as fuels they will release CO2 in the process, but it’s CO2 that’s been sequestrated in the first place, so it’s neutral just like biodiesel (see “biodiesel, not that green after all”). It’s only neutral, of course, if the energy that goes into producing the alcohol or biodiesel doesn’t release additional CO2. As such, the authors envision that a sensible power source for the process is renewable energy. In fact, the alcohol made from CO2 could be a solution to another problem: storing energy from solar or wind power.

 “We are trying to reduce the CO2 electrochemically,” Stefanie Schlager, a doctoral student at Johannes Kepler University, Linz, Austria, told a session at the Materials Research Society’s fall meeting in Boston last week.

Similarly, last year we reported the findings of a group from the US found a way to transform the carbon dioxide trapped in the atmosphere into useful industrial products. Their process involved using a microorganism in special conditions to achieve this, however the energy input required to meet these conditions are tremendous and as such the process is totally impractical. Now, if you ask me, the most interesting carbon sequestration technique comes from the UK. There, at University of Newcastle, researchers found a way to react gaseous CO2 with low grade minerals such as magnesium and calcium silicate to produce limestone, a common and important constructions material. The group was awarded a $9 million grant and is the process of building a pilot plant.

Acacia tree

Acacia trees deal addiction to bodyguard ants

A strange evolutionary alliance between trees and the ants that guard them has a sinister explanation, a new study suggests, after studying ants hooked on nectar.

Bodyguard ants and addiction

In Central America, ants act as bodyguards for acacia trees, defending them not only from weeds, but also from animals, in exchange for accomodation and food – this has traditionally been seen as one of the most consistent and remarkable alliances in nature.

But Martin Heil of Cinvestav Unidad Irapuato in Mexico reports there’s more than meets the eye when it comes to tree snacks. The tree’s sugary offerings are laced with an enzyme that prevents the ants from eating other sources of sugar – one sip, and they’re hooked to the tree and only the tree, in classic type of addiction.

“It was surprising to me that the immobile, ‘passive’ plant can manipulate the seemingly much more active partner, the ant,” says Heil.

The report illustrates how even in the seemingly mutually advantageous partnerships in nature, one part takes more out of the deal than the other.

Heil compares the situation to a dairy company that sells lactose-free milk chemically altered to render its customers unable to digest normal milk. Drink it, and you can only eat that brand forever.

Sneaky trees

Acacia tree

photo credit: angela7dreams

Ants love eating sweet foods; most of the foods they eat, such as plant sap, are rich in a sugar called sucrose. The ants digest this with an enzyme called invertase, which basically breaks the sucrose into smaller sugars. In 2005, Heil had previously shown that all of the workers of the acacia ant Pseudomyrmex ferrugineus lack invertase – and therefore cannot digest sucrose. Fortunately for them, the tree compensates for this impairment by secreting invertase into its nectar, providing the ants with a predigested meal. Quite a neat trick, apparently, but isn’t it a little just too perfect? It does seem a little strange, how things worked out just fine, so Heil set out to understand what happens behind the curtain.

What he found out was that the tree’s sugary treats not only contained invertase, but they also contained something extra – chitinase enzymes that completely block invertase development in ants. So basically the tree takes away their ability to digest, and instead, offers them pre-digested food, quite a neat, sneaky trick.

“Ain’t nature grand?” says Todd Palmer of the University of Florida, who studies ants and acacias. “What looks from the outside as another case of digestive specialization appears to be a sneaky manipulation on the part of the acacia to increase ant dependence.”

Enzymes and bodyguards

Now, researchers want to go even deeper, and find out exactly how a plant’s chitinase could block an ant’s invertase.

“All the biochemists whom I talked to told me that there is no way one of these enzymes can inhibit the other. There is simply no known biochemical mechanism through which this could happen,” he says. “It adds to our understanding of why co-evolved systems persist even when they may not be required for both partners,” says Corrie Moreau, an evolutionary biologist from the Field Museum in Chicago.

So either he’s missing something, or this is truly a revolutionary mechanism. But there’s another interesting question: why don’t young workers try another food source, while their digestive system hasn’t been tampered? Heil thinks this is because nectar is almost always their first adult meal, either because it is the closest food or because the ants are fed the nectar by their nest-mates.

“Since the first dose of nectar is enough to reduce invertase activity, they remain trapped,” he says.

Scientific Reference: Partner manipulation stabilises a horizontally transmitted mutualism
Martin Heil1,*, Alejandro Barajas-Barron1, Domancar Orona-Tamayo1,2, Natalie Wielsch3, Ales Svatos3

soda_water_cure_hangover

‘Sprite’ and soda water best cures against hangover

Drinking until the early hours of dawn may be exhilarating for some, however the next day everything seems to tumble over as the mind is assaulted by a barrage of hangover attacks. There are a number of popular home-brewed remedies against hangover: eating eggs, sipping a bit of castor oil, Vitamin B effervescent pills, tomato sauce, work (or anything that keeps you distracted from the pain) or even more alcohol. Anthony Burgess, famous writer known as the author of A Clockwork Orange,  liked to beat his hangovers to the finish line with a homemade cocktail that rarely left him feeling weary – a concoction known as Hangman’s Blood. “Into a pint glass, doubles of the following are poured: gin, whisky, rum, port and brandy. A small bottle of stout is added and the whole topped up with Champagne … It tastes very smooth, induces a somewhat metaphysical elation, and rarely leaves a hangover,” he instructs.

soda_water_cure_hangoverScientists however warn that drinking more alcohol, even beer, doesn’t help with hangovers. More alcoholic drinks will only boost the existing toxicity of the alcohol already in one’s body, and may lead to further drinking, according to previous research (National Institute on Alcohol Abuse and Alcoholism). With a hangover, you’re most likely suffering from dehydration and a deficiency of important minerals like magnesium and potassium. Symptoms of dehydration include headache, cottonmouth, lightheadedness, and thirst.  Drinking water is an obvious first step anyone should take following a night out drinking. Often than not that’s not enough, so what would be effective against hangovers?

A recent research performed by Chinese researchers found that what you drink following alcohol consumption can have a significant effect on one’s hangover symptoms – that is to say, you can alleviate or worsen it. The researchers made tests on several beverages, including teas and various carbonated drinks. According to their findings the carbonated drink Sprite, as well as soda water, helped cure hangovers the most.

Curing a hangover

It’s important to understand what causes hangovers or better said what are the mechanisms that lead to a hangover. A popular assumption is that the adverse effect of consuming alcohol is caused by ethanol. In reality, ethanol’s first metabolite –  acetaldehyde – is what causes the dreaded feeling. The compound is metabolized by the enzyme alcohol dehydrogenase (ADH) and then into acetate by aldehyde dehydrogenase (ALDH). Acetate is actually thought to be responsible for some of the positive health benefits of alcohol consumption, so the key to alleviating post-alcohol consumption hangover is to control acetaldehyde through the dehydrogenase enzyme.

University in Guangzhou researchers tried various drinks which based on their chemical content they hypothesized these might interact with dehydrogenase in some way – either promoting or inhibiting its use. Some of the drinks tested, including a herbal infusion known as Huo ma ren, were found to increase the activity of ADH, accelerating the metabolization of ethanol into the toxic acetaldehyde. Therefore consuming these drinks will actually increase your hangover.

Other drinks, however,  markedly increased ALDH activity, thus promoting the rapid break-down of acetaldehyde and could minimise the harmful effects of drinking alcohol. These drinks include Xue bi and Hui yi su da shui or the carbonated drinks known in English as Sprite and soda water, respectively. According to the paper, soda water consumption reduced alcohol dehydrogenase (ADH) activity by 5.7% and also increased acetaldehyde dehydrogenase activity by 49.3%. This minimises the exposure to acetaldehyde.

 

Cure for the hangover possibly found

In a promising discovery for students and party aninals all over the world, a team of researchers led by UCLA engineers has identified a method for speeding up the body’s reaction to alcohol consumption – practically elimining the hangover.

drinks

Researchers take their hangovers really seriously – in a paper published online Feb. 17 in the peer-reviewed journal Nature Nanotechnology, Yunfeng Lu, a professor of chemical and biomolecular engineering at UCLA, successfully placed two complementary enzymes in a tiny capsule to speed up the elimination of alcohol from the body. Basically, when you drink, your liver starts processing the alcohol. It works and works, and after a while, it’s just overwhelmed. This pill does pretty much the same thing – it essentially processes alcohol the way the liver does.

“With further research, this discovery could be used as a preventative measure or antidote for alcohol intoxication.”

The researchers used a mouse model to test how well the enzyme package worked as an antidote after alcohol was consumed. After they got the mice drunk and served them the enzymes, they found that blood alcohol levels dropped significantly – 15.8 percent lower than the control group after 45 minutes, 26.1 percent lower after 90 minutes and 34.7 percent lower after three hours.

The researchers believe this is just the beginning.

“Considering the vast library of enzymes that are currently or potentially available,” the authors write, “novel classes of enzyme nanocomplexes could be built for a broad range of applications.”

he required enzymes are tied together using a DNA tether before being coated in a thin layer of polyacrylamide © NPG

Scientists sober up mice with novel enzyme nano-parcels

A team of international researchers from US and China have employed a novel method to link enzymes together and then encapsulate them in a polymer shell. This enables the enzymes to work sequentially in chemical reactions, just like in nature. To illustrate their enzyme batch, a group of mice were intoxicated with alcohol and then injected with a packaged enzyme complex that metabolises alcohol. Those injected with the package dramatically sobered up within a few hours, while non-injected mice laid drunk as a skunk.

“In eukaryotic cells, most enzymes do not freely diffuse within the cytosol, but are spatially defined within subcellular organelles or closely co-localised as enzyme complexes along with other enzymes,” explains team member Yunfeng Lu, of the University of California, Los Angeles. “In consecutive reactions catalysed by multiple enzymes, such close confinement minimises the diffusion of intermediates among the enzymes, enhancing overall reaction efficiency and specificity. Meanwhile, toxic intermediates generated during a metabolic process are promptly eliminated by the nearby enzymes co-localised within the confined structures.”

Delivering a set of complex enzymes in the right order is very challenging, and typically implies  fabrication of delivery systems, such as liposomes or nano-carriers, first and then the enzymes are encapsulated into the carriers passively. In the method employed by the researchers, however, an alternate, more neat route is taken.

he required enzymes are tied together using a DNA tether before being coated in a thin layer of polyacrylamide © NPG

he required enzymes are tied together using a DNA tether before being coated in a thin layer of polyacrylamide © NPG

Lu and colleagues devised a way to bring various enzymes together and spin a sort of polymer cocoon around them. The first step is to identify inhibitors – molecules that will specifically attach to a given enzyme. A number of different inhibitors – each specific to its own enzyme – are then linked by a string of DNA. In the presence of the different enzymes, each inhibitor hooks its own enzyme, trapping them around the DNA scaffold and creating a complex. Gentle heating then removes the DNA scaffold and inhibitors, leaving the functioning enzymes encased within the polymer.

The concept was demonstrated with a complex of alcohol oxidase and catalase which can remove alcohol from the bloodstream – quite handy, I might add. The alcohol oxidase reacts with ethanol and oxidizes it into acetaldehyde and hydrogen perodixe. Now, the latter is toxic, so if you had only tried alcohol oxidase then you would have been in a lot of trouble. Luckily, the second enzyme, catalase, breaks up the hydrogen peroxide into oxygen and water.

The complex was tried in mice, subsequently fed with alcohol. Naturally, the animals became intoxicated rapidly and fainted within minutes. Some of the mice were injected with the complex and these were found to have recovered a lot faster than those who hadn’t been injected. More exactly, blood alcohol levels were reduced by around 35% over three hours. Neat trick isn’t it?

Now, don’t be fooled into thinking the scientists were just looking for ways to get drunk, sober, drunk, sober, and so on in a repeating fashion – thought this too might have been a goal. As well as providing a route for a possible antidote to alcohol poisoning, Lu says that the method can be generalised for different combinations of enzymes. ‘Through judicious choice of enzymes, we expect to be able to construct a novel class of complexes with programmable, complementary or synergistic functions.’

Findings were reported in the journal Nature Nanotechnology.

Genetic tweak makes plants produce enzyme-replacing drug

Culturing mammalian cells is currently the only way to make some complex proteins used in certain drugs; but growing such cultures is an extremely difficult and delicate job, because they can harbor human pathogens and must therefore be kept under strict temperature conditions.

It’s a difficult job, but it’s definitely worth it; take a look at the rare lysosomal storage disease mucopolysaccharidosis I, for example – it’s as dangerous as it sounds, and it’s only treated with enzyme-replacement therapy. The enzymes must be produced in cells and this brings up huge production costs, which means, of course, very high costs, going up to hundreds of thousands of dollars a year.

This is where Allison Kermode, a plant biologist at Simon Fraser University in Burnaby, Canada, stepped in. Her husband works with people who have lysosomal storage disorders, and she decided to find a way to manufacture the necessary enzymes in plants – maize (corn) to be more precise. The thing is, you can insert human enzymes in plants, but they will be ‘decorated’ with sugar molecules specific in plants – but Kermode and her colleagues found a way to avoid these decorations.

The team tweaked the genes responsible for the production of the protein, not to alter the production itself, but to prevent the proteins from moving into the Golgi complex, a structure where the problematic sugars are added. The Golgi apparatus, as it is already known packages proteins inside the cell before they are sent to their destination; it is particularly important in the processing of proteins for secretion. The approach has been described as ‘very elegant’ by biologists.

It has to be said, we are still pretty far away from putting these drugs on the shelves, but Kermode’s research has proven to be functional, even though the resulting enzymes haven’t been tested on humans. The team also needs to ensure that the seeds produce the protein in higher quantities, but if all goes well, and there’s no reason to believe it won’t, maize may one day become the go-to way to make complex protein drugs.

Source: Nature Commun

flatworm

Scientists prove ‘immortal worms’ can regenerate indefinitely and stay forever young

flatworm

University of Nottingham scientists spurred a slew of debate in 2008 when they claimed their object of study, the planaria or “flatworm”, might actually be immortal, possessing an indefinite ability to regenerate its cells and thus practically never grow old. In fact, an important distinction must be made, it’s not that the flatworm never grows old that’s interesting, it’s the fact that it stays forever young!

As you can imagine a discovery of such interest didn’t go unnoticed, and it wasn’t long before the essential question was put – how do you really know that they’re immortal? A simple question, with an extremely complicated answer. To answer this question, you must first define what makes an animal immortal in the first place. Simply standing by an allegedly immortal animal waiting for it to die is far from being practical at all, in scientific terms. The researchers identified a number of genetic criteria which need to be filled in order for an animal to be considered immortal. First of all, it needs to retain the ability of replacing old cells with new cells indefinitely, and this is what stem cells are for.

Most animal in the world gradually tend to lose this ability as they age, thus causing them to get older, function improperly and eventually die. The flatworm not only is able to regenerate its old, dead cells, but it can literary grow a new brain, gut or tail when severed in two. Both cut ends grow into a new individual. Over the course of their several year long research, Notthingham University scientists have cloned a few thousand individuals starting from one single flatworm that was cut in two, which were also at their own term cut in two, and so on so forth. Biologist Dr. Aziz Aboobaker, who heads the project explains:

“We’ve been studying two types of planarian worms; those that reproduce sexually, like us, and those that reproduce asexually, simply dividing in two,” said Dr. Aziz Aboobaker from the University’s School of Biology.

“Both appear to regenerate indefinitely by growing new muscles, skin, guts and even entire brains over and over again.

“Usually when stem cells divide — to heal wounds, or during reproduction or for growth — they start to show signs of aging. This means that the stem cells are no longer able to divide and so become less able to replace exhausted specialized cells in the tissues of our bodies.

“Our aging skin is perhaps the most visible example of this effect. Planarian worms and their stem cells are somehow able to avoid the aging process and to keep their cells dividing.”

The key lies in DNA

Each time a cell divides, the tip of its DNA, called the telomere, gets shorter. An enzyme called telomerase regenerates the telomores, however in most sexually reproductive organisms it is only active during the organism’s development. Once it reaches maturity, the enzyme stops functioning, and the telomeres become shorter and shorter until cell replication is made impossible, otherwise the DNA would become too severely damaged. An immortal animal is able to maintain telomere length indefinitely so that they can continue to replicate, and Dr. Aboobaker and colleagues were able to demonstrate that the flatworms actively maintain the ends of their chromosomes in adult stem cells, leading to theoretical immortality.

Doctoral student Thomas Tan performed a series of crucial experiments, as part of the project, in order to scientifically explain the worm’s fascinating, yet theoretical, immortality. A possible planarian version of the gene coding for the telomerase enzyme was identified, and had its activity turned off. Since the telomere shrank in size, it was thus confirmed to be the right gene. Armed with this new found knowledge, the scientists monitored and measured the gene and observed that asexual worms dramatically increase the activity of this gene when they regenerate, allowing stem cells to maintain their telomeres as they divide to replace missing tissues.

“It was serendipitous to be sandwiched between Professor Edward Louis’s yeast genetics lab and the Children’s Brain Tumour Research Centre, both University of Nottingham research centres with expertise in telomere biology. Aziz and Ed kept demanding clearer proof and I feel we have been able to give a very satisfying answer,” Dr. Tan stated.

From immortal worms to immortal humans

The same didn’t apply to sexual flatworms, though, which still, however, display the same apparently indefinite ability to regenerate. The researchers explain that either these flatworms will eventually shorten their telomeres, albeit very gradually, or they found a different way to maintain indefinite cell replication that doesn’t involve the telomerase  enzyme.

The researchers claim that the next natural step is to study how this might apply to more complex organisms, like humans.

“The next goals for us are to understand the mechanisms in more detail and to understand more about how you evolve an immortal animal,” said Aboobaker.

“The worms are a model system in which we can ask questions, like is it possible for a multicellular animals to be immortal and avoid the effects of aging?”

“If so, how does this animal do this in comparison to animals that don’t? Of course we hope that this impacts humans, that’s why we do it. But we aren’t planning on making any drugs or medicines… other people are, I’m sure.”

The findings were published in the journal PNAS. University of Nottingham PR

Enzyme allows mice to eat more, and gain less weight

Mice altered to express the IKKbeta enzyme (right column) in their fat had smaller globules of fat in their subcutaneous adipose tissue (top row) and in their liver (bottom row) than normal mice (left column). (Credit: Xu Lab)

Scientists have genetically engineered mice able to express a certain enzyme, which allows for an increased metabolic rate. The lab mice infussed with this enzyme in their fat tissue were able to eat more, but gain far less weight than their naturally bred brethren.

It’s generally acknowledged that obesity and inflammation cause insulin resistance, however it’s not perfectly understood why this happens. Embarking on a research that seeks to clarify how obesity and inflammation affect insulin resistance, Brown University researchers changed the sequence of events for transgenically engineered mice by inducing inflammation via the IKKbeta enzyme in their fatty tissue before they were obese.

They then procedeed in administrating a fatty diet to two groups of mice, one altered, the other natural, with all mice starting at the same weight. They observed that 22 weeks on a high-fat diet, however, altered male mice weighed less than 38 grams while unaltered male mice weighed more than 45 grams. After switching to a less fatty diet, the weight differences between the two groups weren’t as evident, however they remained statistically significant.

“Turning on this molecule has a very dramatic impact on lipid metabolism,” says Haiyan Xu, assistant professor of medicine at Brown University and corresponding author of a paper describing the research published online in the journal Endocrinology.

The altered mice not only managed to eat more and gain less weight, but due to their accelerated metabolism, researchers could observe they had lower sugar levels in their blood, after a glucose shot, than those of the control mice. An insulin shot was also administered, and researchers also remarkably observed how insulin was more effective.

Scientists are now trying to figure out the mechanisms through which IKKbeta enzyme can increase metabolic performance. One thing’s for certain for the researchers responsible for the study: obesity and inflammation are both promoters of insulin resistance, and obesity seems to be the worse one, Xu says. “Lower body weight is always a beneficial thing for influencing insulin sensitivity. Reduced adiposity wins over increased inflammation.”

source

Ingame screenshot of the Foldit interface.

Gamers solve decade old HIV puzzle in ten days

Scientists from the University of Washington have been struggling for the past decade to decipher the complex structure of an enzyme that exhibits  behavior similar to that of an enzyme key in the development of AIDS from an HIV infection, and which might hold a critical role in building a cure for the disease. Gamers playing spatial game Foldit have managed to collectively determine the enzyme’s structure in ten days.

Puzzled by the intricate structure of the M-PMV retroviral protein, an enzyme that plays a key role in the development of a virus similar to HIV, scientists have striven to find its chemical key for ten years now. Each enzyme has millions of possible combination in which it can fold its atom bonds, and determining its precise structure is a very laborious enterprise even for high-end computers with large processing power.

Ingame screenshot of the Foldit interface.

Ingame screenshot of the Foldit interface.

As a long-shot University of Washington biologists sent the virtual 3D model of the M-PMV to the online game Foldit, where gamers folded and turned it into a myriad of combinations. Eventually, and remarkably enough, the gamers obtained the optimum one – the state that needed the lowest energy to maintain.  Now unlocked, scientists have a concrete means of understanding how the enzyme works, and consequently how to attack it.

“This was really kind of a last-ditch effort. Can the Foldit players really solve it?” Firas Khatib, a biochemist at the University of Washington and the lead author on the recently published research paper told MSNBC. “They actually did it in less than 10 days.”

Foldit is a very simple game, which tackles biology’s biggest issue – folding proteins. To play the game you don’t need any biology background, just your native spatial reasoning skills. Motivation comes in the form of competition, and from this stand point, the game has been more than suitably designed. Basically you get scored for three factors: how well you pack the protein, how efficiently you hide the hydrophobics and how you clear the clashes.  Trust me, it’s a lot simpler than it sounds.

“Foldit attempts to predict the structure of a protein by taking advantage of humans’ puzzle-solving intuitions and having people play competitively to fold the best proteins,” states the game’s website.

“Since proteins are part of so many diseases, they can also be part of the cure.

Protein folding had proved to be one of the more popular uses for distributed computing
“Players can design brand new proteins that could help prevent or treat important diseases.”

The game allows players to chat with each other and collaborate, thus various gamers built up each others work and  collectively managed to crack the code for the most energy efficient enzyme structure – the most important structure to study.

The reason why computers haven’t been able to do this, despite their evidently superior processing capabilities, is that they’re still far from being capable of having human-like spatial reasoning. Interestingly enough, Foldit records the players’ actions and processes them in an algorithm which will eventually help the AI behind the game to someday be able to compile successful structures on its own.

Seth Cooper, a University of Washington computer scientist and lead designer and developer of Foldit, is hoping that more scientists send them problems that fit within the Foldit format.

“The critical role of Foldit players in the solution of the M-PMV [retroviral protease] structure shows the power of online games to channel human intuition and three-dimensional pattern-matching skills to solve challenging scientific problems,” said the study, which was published by Nature Structural & Molecular Biology. “Although much attention has recently been given to the potential of crowdsourcing and game playing, this is the first instance that we are aware of in which online gamers solved a longstanding scientific problem.”

Still, the breakthrough is amazing by all means. Next time somebody tells you you’re wasting time playing a video game, you can always show them this article and tell them you’re helping save the world.

Article revised 10/16/2013: 1. In the original draft, “Washington University” was mistakenly written instead of “University of Washington”

 2. Grammar fix

3. Initial paragraph was modified, better reflecting reality. 

How aging can be cured in the future – a scientist’s view

If we’re to guide ourselves after Aubrey de Grey‘s telling, according to his predictions the first person who will live to see their 150th birthday has already been born, and as science advances along the decades at the current pace it does, he claims people born soon after the latter mentioned birthday will live to be 1,000.

“I’d say we have a 50/50 chance of bringing aging under what I’d call a decisive level of medical control within the next 25 years or so,” de Grey said in an interview before delivering a lecture at Britain’s Royal Institution academy of science.

“And what I mean by decisive is the same sort of medical control that we have over most infectious diseases today.”

"The Fountain of Youth" painting by Lucas Cranach the Elder. Scientists are trying to prolong life by employing cell and gene treatments.

"The Fountain of Youth" painting by Lucas Cranach the Elder. Scientists are trying to prolong life by employing cell and gene treatments.

As living standards increase worldwide, so does the life expectancy. The world’s longest-living person on record lived to be 122, while in Japan alone there were more than 44,000 centenarians in 2010. This could be counter-acted, however, by the increasing obesity trend which is sweeping the world, which due to a high comfort level and sedentary life style has exposed people to other life treating issues.

As we age, molecular and cellular damage occurs in our body in brain, with minimum recovery. Some people manage to shelter themselves through out their lives from various sources of damage (hard physical labor, stress, diseases etc.), and live longer than the average individual. Dr. de Grey sees a time when people will go to regular maintenance checks, in which their cellular and molecular damage would be then treated through various means, like gene therapies, stem cell therapies, immune stimulation and a range of other advanced medical techniques to keep them in good shape.

“The idea is to engage in what you might call preventative geriatrics, where you go in to periodically repair that molecular and cellular damage before it gets to the level of abundance that is pathogenic,” he explained.

Part of the technology necessary to employ these sorts of longevity treatments are already existing, like stem cells treatment which is used for spinal cord injuries, as well as brain and heart related medical issues. Some, though, like heart-related failures are still extremely complicated to solve, and de Grey says there is a long way to go on these though researchers have figured out the path to follow.

The most common heart failure causing diseases surface as a result of byproducts of the body’s metabolic processes which our bodies are not able to break down or excrete. Scientists are now trying to identify enzymes that handle this process of cleansing in other species, and though gene therapy to dramatically lower the risk of a patient having a heart attack or stroke.

“The garbage accumulates inside the cell, and eventually it gets in the way of the cell’s workings,” he said.
“If we could do that in the case of certain modified forms of cholesterol which accumulate in cells of the artery wall, then we simply would not get cardiovascular disease,” de Gray went on.

It’s not about making the world of the future a viable place for the elderly zombies or vegetables. One could imagine a 150 year old man to be no more than some skin hanging on to a skeleton. Dr. de Gray argues that this kind of point isn’t on par with the idea of longevity – that of expanding one’s life span, while improving the health directly proportionally.

“This is absolutely not a matter of keeping people alive in a bad state of health,” he told Reuters. “This is about preventing people from getting sick as a result of old age. The particular therapies that we are working on will only deliver long life as a side effect of delivering better health.”

Dr. de Grey’s prospects sound terribly exiting and frightning at the same time, but his credibility has been challenged in recent past years, formally by a group of nine leading scientists who dismissed his work as “pseudo science.” In response, the MIT Technology Review journal which saw de Grey’s work as forward-thinking and based on ideas yet-to-be-tested by interesting enough for other scientists to follow, offered $20,000 in 2005 for any molecular biologist who showed that de Grey’s SENS theory was “so wrong that it was unworthy of learned debate”. The prize money has never been won to this date.

De Grey’s has been relunctant to give any precise predictions on how long people would be able to live in the future, but what’s very sure about is that in the future as technology and science advance we buy ourselves even more time.

“I call it longevity escape velocity — where we have a sufficiently comprehensive panel of therapies to enable us to push back the ill health of old age faster than time is passing. And that way, we buy ourselves enough time to develop more therapies further as time goes on,” he said.

“What we can actually predict in terms of how long people will live is absolutely nothing, because it will be determined by the risk of death from other causes like accidents,” he said.

“But there really shouldn’t be any limit imposed by how long ago you were born. The whole point of maintenance is that it works indefinitely.”