Tag Archives: Genetics

Electronic gene control could let us plug bacteria into devices

Pink bacterium with purple background

We don’t usually welcome bugs in digital technology, but that’s about to change. Researchers have developed a way to control bacterial genes at the flick of a switch using electricity.

Synthetic biologists are eager to find ways to connect engineered organisms to electronics, so we can make living components for devices.

The ability of custom-made microbes to sense the environment and make biological molecules would be particularly valuable for devices that work inside the body, says William Bentley at the University of Maryland.

“If you want to discover what’s going on in the gastrointestinal tract or the oral cavity, if you can connect to electronics you have a way of interpreting what’s going on and you may be able to manipulate it,” he says.

For example, a device could use an organism to sense chemicals produced by harmful bacteria in the body and secrete an antibiotic when it detects them.

To get specific genes in bacteria to respond to electrical stimulation, Bentley’s team took advantage of what are called redox molecules. These biological molecules are found in all cells and can pick up and pass on electrons. They are said to have a reduced state when they gain electrons, and an oxidised state when they lose electrons.

The team also made use of naturally occurring genetic components in E. coli that respond to oxidative stress, which occurs when too many molecules in the cell are o apply electrical input, the researchers submerged an electrode in a liquid containing the bacteria. When the electrode supplies a positive charge, certain redox molecules get oxidised and trigger the genetic mechanisms that respond to oxidative stress.

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Tiny, Vast Windows Into Human DNA by Carl Zimmer

In the history of biology, two little animals loom large.

In the early 1900s, scientists began studying Drosophila melanogaster, the common fruit fly. Research on these fast-breeding insects revealed that genes lie on chromosomes, which turned out to be true for other animals, including us. For more than a century, scientists have continued to glean clues from the lowly fly to other mysteries of biology, like why we sleep and how heart disease develops.

In the 1960s, another unassuming animal joined biology’s pantheon: a tiny worm called Caenorhabditis elegans. The biologist Sydney Brenner realized that its body, made up of just a couple of thousand cells, offered an singular opportunity to learn how a single egg gives rise to a complete animal. Today, many scientists are studying the worm for clues to how our own brains are wired and why we age.

Now the two species are providing even deeper insights in biology. A team of hundreds of scientists has exhaustively recorded the choreography of their genes as the animals develop from eggs to adults.

“It’s not just this gene or that gene,” said Robert H. Waterston, a geneticist at the University of Washington who is among the scientists working on the project, called modENCODE. “We can get a picture of the whole.”

Dr. Waterston and his colleagues published overviews of the modENCODE results in five papers last week in Nature. In their initial analysis, they find a striking similarity between the choreography of genes in flies and worms and that of our own DNA. Exploring that similarity may provide scientists with new insights into genetic disorders and diseases like cancer.

In 1998, Dr. Waterston and a large group of fellow scientists cataloged all 19,000 protein-coding genes in C. elegans, along with a rough guide to the rest of its DNA. In 2000, researchers did the same for D. melanogaster. These two efforts were a huge help to scientists studying the biology of the animals. But these two efforts revealed little about what the genes actually do in an organism. It was as if they had inventoried all the instruments in an orchestra but weren’t able to see the sheet music.

A gene contains information that a cell can use to make a particular molecule. But an animal may only use a given gene at a particular time in its life, or in a particular organ.

Cellular DNA is coiled around spool-like molecules called histones. When DNA is tucked away, gene-reading molecules cannot reach it. By adding certain compounds, known as histone marks, to the histones, a cell opens up a stretch of DNA.

When a gene is exposed this way, a protein called a transcription factor latches onto it, recruiting other molecules to “read” it and produce a new protein or RNA molecule. Sometimes, a single transcription factor may switch on dozens of other genes. And sometimes, those genes encode transcription factors of their own, enabling a cell to produce hundreds of kinds of molecules at once.

The modENCODE team took on an enormous task: to create a detailed picture of this molecular dance. For the past five years, hundreds of biologists have been recording DNA activity in flies and worms, and systematically comparing the results to what they see in humans.

To study genes in humans, the scientists focused on a wide variety of cells, like neurons, blood cells and liver cells. In the experiments on flies and worms, the scientists examined the entire bodies of the animals as they matured from eggs.

The scientists cataloged the parts of the genome that cells were using. They also mapped the histone marks and located the transcription factors latching onto the DNA. Because the scientists used the same methods to gather data from all three species, they were able to compare them on a scale never before attempted.

Flies, worms and humans come from distant branches on the evolutionary tree. The last common ancestor lived 700 million years ago. Despite the tremendous differences among the three species, the modENCODE team found some striking parallels in the workings of their DNA.

In all three, it turned out, many genes tended to turn on and off in the same pattern, following a predictable rhythm. All told, the researchers found 16 such sets of genes, each containing hundreds of genes working together. While it’s not clear yet what these genes are doing in all three species, the scientists did observe that a dozen clusters were especially active at some stages of development in the worm and the fly. They may be essential for transforming an egg into an adult animal.

The scientists also found that histone marks control DNA in much the same way in all three species. If certain marks were present around a gene, the scientists usually could predict how active it was, whether fly, worm or human.

“The neat thing is that it works — it really works well,” Mark Gerstein of Yale University, a modENCODE team member, said of the group’s predictive model.

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How the zebra got its stripes, with Alan Turing

3.turing72-03 © Job Boot for Mosaic


n 1952 a mathematician published a set of equations that tried to explain the patterns we see in nature, from the dappled stripes adorning the back of a zebra to the whorled leaves on a plant stem, or even the complex tucking and folding that turns a ball of cells into an organism. His name was Alan Turing.

More famous for cracking the wartime Enigma code and his contributions to mathematics, computer science and artificial intelligence, it may come as a surprise that Turing harboured such an interest. In fact, it was an extension of his fascination with the workings of the mind and the underlying nature of life.

The secret glory of Turing’s wartime success had faded by the 1950s, and he was holed up in the grimly industrial confines of the University of Manchester. In theory he was there to develop programs for one of the world’s first electronic computers – a motley collection of valves, wires and tubes – but he found himself increasingly side-lined by greasy-fingered engineers who were more focused on nuts and bolts than numbers. This disconnection was probably intentional on Turing’s part, rather than deliberate exclusion on theirs, as his attention was drifting away from computing towards bigger questions about life.

It was a good time to be excited about biology. Researchers around the world were busy getting to grips with the nature of genes, and James Watson and Francis Crick would soon reveal the structure of DNA in 1953. There was also a growing interest in cybernetics – the idea of living beings as biological computers that could be deconstructed, hacked and rebuilt. Turing was quickly adopted into a gang of pioneering scientists and mathematicians known as the Ratio Club, where his ideas about artificial intelligence and machine learning were welcomed and encouraged.

Against this backdrop Turing took up a subject that had fascinated him since before the war. Embryology – the science of building a baby from a single fertilised egg cell – had been a hot topic in the early part of the 20th century, but progress sputtered to a halt as scientists realised they lacked the technical tools and scientific framework to figure it out. Perhaps, some thinkers concluded, the inner workings of life were fundamentally unknowable.

Turing viewed this as a cop-out. If a computer could be programmed to calculate, then a biological organism must also have some kind of underlying logic too.

He set to work collecting flowers in the Cheshire countryside, scrutinising the patterns in nature. Then came the equations – complex, unruly beasts that couldn’t be solved by human hands and brains. Luckily the very latest computer, a Ferranti Mark I, had just arrived in Manchester, and Turing soon put it to work crunching the numbers. Gradually, his “mathematical theory of embryology”, as he referred to it, began to take shape.

Like all the best scientific ideas, Turing’s theory was elegant and simple: any repeating natural pattern could be created by the interaction of two things – molecules, cells, whatever – with particular characteristics. Through a mathematical principle he called ‘reaction–diffusion’, these two components would spontaneously self-organise into spots, stripes, rings, swirls or dappled blobs.

In particular his attention focused on morphogens – the then-unknown molecules in developing organisms that control their growing shape and structure. The identities and interactions of these chemicals were, at the time, as enigmatic as the eponymous wartime code. Based on pioneering experiments on frog, fly and sea urchin embryos from the turn of the 20th century – involving painstakingly cutting and pasting tiny bits of tissue onto other tiny bits of tissue – biologists knew they had to be there. But they had no idea how they worked.


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