Category: Molecular biology

Gangs of corrupted proteins spread through mouse brains and cause Parkinson’s-like symptoms

By Ed Yong | November 15, 2012 4:00 pm

This post contains material from an older one, updated based on new discoveries.

There are many things you don’t want gathering in large numbers, including locusts, rioters, and brain proteins. Our nerve cells contain many proteins that typically live in solitude, but occasionally gather in their thousands to form large insoluble clumps. These clumps can be disastrous. They can wreck neurons, preventing them from firing normally and eventually killing them.

Such clumps are the hallmarks of many brain diseases. The neurons of Alzheimer’s patients are riddled with tangles of a protein called tau. Those of Parkinson’s patients contain bundles, or fibrils, of another protein called alpha-synuclein. The fibrils gather into even larger clumps called Lewy bodies.

Now, Virginia Lee from the University of Pennsylvania School of Medicine has confirmed that the alpha-synuclein fibrils can spread through the brains of mice. As they spread, they corrupt local proteins and gather them into fresh Lewy bodies, behaving like gangs that travel from town to town, inciting locals into forming their own angry mobs. And as these mobs spread through the mouse brains, they reproduce two of the classic features of Parkinson’s disease: the death of neurons that produce dopamine, and movement problems.

This is the clearest evidence yet that alpha-synuclein can behave like prions, the proteins that cause mad cow disease, scrapie and Creutzfeld-Jacob disease (CJD). Prions are also misshapen proteins that convert the shape of normal peers. But there is a crucial distinction: prions are infectious. They don’t just spread from cell to cell, but from individual to individual. As far as we know, alpha-synuclein can’t do that.

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MORE ABOUT: Lewy, Parkinson's, synuclein

A network of molecules, building each other at the dawn of life

By Ed Yong | October 17, 2012 1:00 pm

Every time one of the cells in your body divides, it has to double its quota of DNA so that each daughter cell gets a complete set. DNA is a replicator—a molecule that can be accurately duplicated, admittedly with some help from proteins. DNA has been doing this for billions of years, well before there were humans, before animals existed, and probably before the first cells evolved.

But what came before DNA? Probably RNA, a related molecule. Certain types of RNA can store genetic information, just like DNA. And much like proteins, they can fold into three-dimensional shapes to speed up chemical reactions, among other functions—these are called ribozymes.

The dominant theory is that an “RNA world” preceded the origin of life. It’s possible that the Earth’s first true replicators were RNA molecules that could fold up to speed up their own replication. They copied themselves. They did so imperfectly, creating daughter molecules with slightly different sequences. Some of them copied themselves more efficiently, and left more descendants than their peers. Gradually, the entire population evolved towards ever more efficient replication.

But there’s a problem with this story. The RNA molecule we’re talking about would have been long and folded into a complex ribozyme. But the ribozymes that scientists can make today are simple, and made from very short pieces of RNA. You can imagine a simple molecule gradually growing and evolving into a more complex one, but that idea has problems too. Mathematical models predict that this burgeoning replicator would be unable to copy itself accurately enough, and would start accumulating errors. After a while, it would face an “error catastrophe”, where the build-up of mistakes crippled it.

But what if there wasn’t just one RNA replicator copying itself? What if, instead, there was a whole network of them? This idea was originally floated in 1971 by Nobel-winning chemist Manfred Eigen. “He came to the conclusion that an individual replicator couldn’t persist for very long, and came up with the idea of a hypercycle,” says Niles Lehman from Portland State University. That is, molecule A helps B to copy itself. B helps C, C helps D and so on, eventually looping back to A.

Eigen predicted the existence of hypercycles using mathematics. Now, Lehman has created something similar in a test tube. It’s a contrived set-up, and it doesn’t confirm that such networks were genuinely involved in the origin of life, but it shows that they can form, and that they become more complex over time. As James Attwater and Philipp Holliger from the University of Cambridge write in an accompanying piece, the study makes “a persuasive case for the benefits of cooperation even at this nascent stage of life. The first genes may not have been so selfish, after all.”

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CATEGORIZED UNDER: Molecular biology

Painkilling chemicals with no side effects found in black mamba venom

By Ed Yong | October 3, 2012 1:00 pm

The black mamba has a fearful reputation, and it’s easy to see why. It can move at around 12.5 miles (20 kilometres) per hour, making it one of the world’s fastest snakes, if not the fastest. Its body can reach 4.5 metres in length, and it can lift a third of that off the ground. That would give you an almost eye-level view of the disturbingly black mouth from which it gets its name. And inside that mouth, two short fangs deliver one of the most potent and fast-acting venoms of any land snake.

Combined with its reputation for aggression (at least when cornered) and you’ve got a big, intimidating, deadly, ornery serpent that can probably outrun you. It’s not the most obvious place to go looking for painkillers.

But among the cocktail of chemicals in the black mamba’s venom, Sylvie Diochot and Anne Baron from the CNRS have found a new class of molecules that can relieve pain as effectively as morphine, and without any toxic side effects. They’ve named them mambalgins.

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CATEGORIZED UNDER: Molecular biology, Reptiles, Snakes

Transformer protein changes from nunchucks to flower

By Ed Yong | July 19, 2012 1:50 pm

Your body is full of little pieces of origami. They’re proteins – the molecular machines that keep your cells ticking over. Each is a long sequence of amino acids that folds into a complicated three-dimensional shape. The classical view is that the shape is fixed, and set by the protein’s sequence.

But Bjorn Burmann from Ohio State University has found a bacterial protein that can refold into two radically different shapes, each with very different roles. While there are some other proteins that can change shape, none can do so to such a dramatic degree, and many that do cause disastrous brain diseases.

I’ve written about the study for The Scientist, so head over there for the details.

CATEGORIZED UNDER: Molecular biology

As oxygen filled the world, life’s universal clock began to tick

By Ed Yong | May 16, 2012 1:00 pm

The Earth’s earliest days were largely free of oxygen. Then, around 2.5 billion years ago, primitive bacteria started to flood the atmosphere with this vital gas. They produced it in the process of harnessing the sun’s energy to make their own nutrients, just as plants do today. The building oxygen levels reddened the planet, as black iron minerals oxidised into rusty hues. They also killed off most of the world’s microbes, which were unable to cope with this new destructive gas. And in the survivors of this planetary upheaval, life’s first clock began to tick and tock.

Today, all life on Earth runs on internal clocks. These ‘circadian rhythms’ are the reason we feel sleepy at night, and why our hormones, temperature and hunger levels rise and fall with a 24-hour cycle. They’re molecular metronomes that keep the events inside our bodies ticking in time with the world around us.

Until now, it seemed that the major branches of the tree of life each had their own timekeeping systems, evolved independently of the others. But Akhilesh Reddy and John O’Neill from the University of Cambridge have disproved that idea, by finding a universal clock that ticks in all kingdoms of life. “It’s exciting because it shows that circadian rhythms are likely as primitive as life on Earth,” says Erik Herzog from Washington University.

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CATEGORIZED UNDER: Evolution, Molecular biology

Synthetic XNA molecules can evolve and store genetic information, just like DNA

By Ed Yong | April 19, 2012 2:00 pm

Out of all the possible molecules in the world, just two form the basis of life’s grand variety: DNA and RNA. They alone can store and pass on genetic information. Within their repetitive twists, these polymers encode the stuff of every whale, ant, flower, tree and bacterium.

But even though DNA and RNA play these roles exclusively, they’re not the only molecules that can. Vitor Pinheiro from the MRC Laboratory of Molecular Biology has developed six alternative polymers called XNAs that can also store genetic information and evolve through natural selection. None of them are found in nature. They are part of a dawning era of “synthetic genetics”, which expands the chemistry of life in new uncharted directions.

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Scientists transform scar tissue into beating heart muscle

By Ed Yong | April 18, 2012 1:00 pm

In an act of transformation worthy of any magician, scientists have converted scar tissue in the hearts of living mice into beating heart cells. If the same trick works in humans (and we’re still several years away from a trial), it could lead us to a long-sought prize of medicine – a way to mend a broken heart.

Our hearts are made of several different types of cell. These include muscle cells called cardiomyocytes, which contract together to give hearts their beats, and connective cells called cardiac fibroblasts, which provide support. The fibroblasts make up half of a heart, but they become even more common after a heart attack. If hearts are injured, they replace lost cardiomyocytes with scar tissue, consisting of fibroblasts. In the short-term, this provides support for damaged tissue. In the long-term, it weakens the heart and increases the risk of even further problems.

Hearts can’t reverse this scarring. Despite their vital nature, they are terrible at healing themselves. But Deepak Srivastava from the Gladstone Institute of Cardiovascular Disease can persuade them to do so with the right chemical cocktail. In 2010, he showed that just three genes – Gata4, Mef2c and Tbx5 (or GMT)– could transform fibroblasts into new cardiomyocytes.

This only worked in cells growing in a laboratory dish, but it was a start. Srivastava’s team have now taken the next step. By injecting living mice with GMT, they turned some of the rodents’ fibroblasts into cardiomyocytes. Since hearts are already loaded with fibroblasts, Srivastava’s technique simply conscripts them into muscle duty. Best of all, the technique worked even better in the animals than in isolated cells. No transplants. No surgeries. No stem cells. Just add three genes, and watch sick hearts turn into healthier ones.

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OpenLab: The Renaissance Man, and how to become a scientist over and over again

By Ed Yong | December 29, 2011 10:00 am


I originally wrote this feature about the amazing Erez Lieberman Aiden back in June. It’s been one of the most popular posts on Not Exactly Rocket Science over the past year, and it was recently nominated for inclusion in the latest edition of Open Lab, the anthology of the world’s best science blogging. For that reason, I’m giving it another airing.

*******

Erez Lieberman Aiden is a talkative witty fellow, who will bend your ear on any number of intellectual topics. Just don’t ask him what he does. “This is actually the most difficult question that I run into on a regular basis,” he says. “I really don’t have anything for that.”

It is easy to understand why. Aiden is a scientist, yes, but while most of his peers stay within a specific field – say, neuroscience or genetics – Aiden crosses them with almost casual abandon. His research has taken him across molecular biology, linguistics, physics, engineering and mathematics. He was the man behind last year’s “culturomics” study, where he looked at the evolution of human culture through the lens of four per cent of all the books ever published. Before that, he solved the three-dimensional structure of the human genome, studied the mathematics of verbs, and invented an insole called the iShoe that can diagnose balance problems in elderly people. “I guess I just view myself as a scientist,” he says.

His approach stands in stark contrast to the standard scientific career: find an area of interest and become increasingly knowledgeable about it. Instead of branching out from a central speciality, Aiden is interested in ‘interdisciplinary’ problems that cross the boundaries of different disciplines. His approach is nomadic. He moves about, searching for ideas that will pique his curiosity, extend his horizons, and hopefully make a big impact. “I don’t view myself as a practitioner of a particular skill or method,” he tells me. “I’m constantly looking at what’s the most interesting problem that I could possibly work on. I really try to figure out what sort of scientist I need to be in order to solve the problem I’m interested in solving.”

It’s a philosophy that has paid dividends. At just 31 years of age, Aiden has a joint lab at MIT and Harvard. In 2010, he won the prestigious $30,000 MIT-Lemenson prize, awarded to people who show “exceptional innovation and a portfolio of inventiveness”. He has seven publications to his name, six of which appeared the world’s top two journals – Nature and Science. His friend and colleague Jean-Baptiste Michel says, “He’s truly one of a kind. I just wonder about what discipline he will get a Nobel Prize in!”

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How coral snakes cause excruciating pain

By Ed Yong | November 16, 2011 1:00 pm

Everyone has felt pain, and many experience it daily. But for such a universal sensation, it is still a mysterious one. We are only starting to understand the molecules that produce a painful sensation. Nature, however, is well ahead of us. Many animals are armed with chemicals that hijack the nervous systems of their targets, producing feelings of intense pain. They are unknowing neuroscientists, and by studying their weapons, we can better understand how pain manifests in our bodies.

Take the Texas coral snake. This brightly coloured serpent, clad in warning hues of red, black and yellow, usually shies away from confrontation. When it’s threatened, it defends itself with venom that can cause excruciating and unremitting pain.

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MORE ABOUT: coral snake, pain, venom

Extending healthy life by getting rid of retired cells

By Ed Yong | November 2, 2011 2:00 pm

As we get older, many of the cells in our bodies go into retirement. Throughout our lives, they divided time and again, all in the face of radiation bombardments and chemical attacks. Slowly but surely, their DNA builds up damage to that threatens to turn them into tumours. Some repair the damage; others give up the ghost. But some cells opt for a third strategy – they shut down. No longer growing or dividing, they enter a state called senescence.

But they aren’t idle. Senescent cells still secrete chemicals into the body, and some scientists have suggested that they’re responsible for many of the health problems that accompany old age. And the strongest evidence for this claim comes from a new study by Darren Baker from the Mayo Clinic College of Medicine.

Baker has developed a way of killing all of a mouse’s senescent cells by feeding them with a specific drug. When he did that in middle age, he gave the mice many more healthy years. He delayed the arrival of cataracts in their eyes, put off the weakening of their muscles, and held back the loss of their body fat. He even managed to reverse some of these problems by removing senescent cells from mice that had already grown old. There is a lot of work to do before these results could be applied to humans, but for now, Baker has shown that senescent cells are important players in the ageing process.

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