Antibiotic Breakthrough

Oh, by the way, did you see this story about a new breakthrough in antibiotics? For a while now, we have been hearing from the scientific community about how antibiotics were abused over these last many decades and as a result, many classes of the drug no longer work on new, resistant bacteria. This very important discovery could change everything and it is great news!

From BBC:

Antibiotics: US discovery labelled 'game-changer' for medicine
By James Gallagher
Health editor, BBC News website

The decades-long drought in antibiotic discovery could be over after a breakthrough by US scientists.

Their novel method for growing bacteria has yielded 25 new antibiotics, with one deemed "very promising". The last new class of antibiotics to make it to clinic was discovered nearly three decades ago.

The study, in the journal Nature, has been described as a "game-changer" and experts believe the antibiotic haul is just the "tip of the iceberg".

The heyday of antibiotic discovery was in the 1950s and 1960s, but nothing found since 1987 has made it into doctor's hands. Since then microbes have become incredibly resistant. Extensively drug-resistant tuberculosis ignores nearly everything medicine can throw at it.

The researchers, at the Northeastern University in Boston, Massachusetts, turned to the source of nearly all antibiotics - soil. This is teeming with microbes, but only 1% can be grown in the laboratory. The team created a "subterranean hotel" for bacteria. One bacterium was placed in each "room" and the whole device was buried in soil. It allowed the unique chemistry of soil to permeate the room, but kept the bacteria in place for study.

The scientists involved believe they can grow nearly half of all soil bacteria. Chemicals produced by the microbes, dug up from one researcher's back yard, were then tested for antimicrobial properties.

The lead scientist, Prof Kim Lewis, said: "So far 25 new antibiotics have been discovered using this method and teixobactin is the latest and most promising one.

"[The study shows] uncultured bacteria do harbour novel chemistry that we have not seen before. That is a promising source of new antimicrobials and will hopefully help revive the field of antibiotic discovery."

Tests on teixobactin showed it was toxic to bacteria, but not mammalian tissues, and could clear a deadly dose of MRSA in tests on mice.

The researchers also believe that bacteria are unlikely to develop resistance to teixobactin. It targets fats which are essential for building the bacterial cell wall, and the scientists argue it would be difficult to evolve resistance. "Here is an antibiotic that essentially evolved to be free of resistance," said Prof Lewis. "We haven't seen that before. "It has several independent different tricks that minimise resistance development."

There are limits to the discovery of the antibiotic teixobactin, which has yet to be tested in people. It works on only Gram-positive bacteria; this includes MRSA and mycobacterium tuberculosis. It cannot penetrate the extra layer of protection in Gram-negative bacteria such as E. coli. But even if their method does mark a new era of antibiotic discovery there are big questions. Sir Alexander Fleming, who discovered penicillin, warned of the dangers of resistance back in his Nobel prize speech in 1945. Yet even now prescriptions in England are rising, with half deemed "inappropriate" and contributing to the problem.

But can we be trusted with new antibiotics? Or will we make the same mistakes again?

http://www.bbc.com/news/health-30657486

Bio-Computers!

This reminds me of the David Cronenberg film "eXistenZ"...

This incredible piece of scientific news yesterday comes from Stanford School of Medicine. The possibilities are mind-boggling.

Biological transistor enables computing within living cells, study says
BY ANDREW MYERS

When Charles Babbage prototyped the first computing machine in the 19th century, he imagined using mechanical gears and latches to control information. ENIAC, the first modern computer developed in the 1940s, used vacuum tubes and electricity. Today, computers use transistors made from highly engineered semiconducting materials to carry out their logical operations.

And now a team of Stanford University bioengineers has taken computing beyond mechanics and electronics into the living realm of biology. In a paper published March 28 in Science, the team details a biological transistor made from genetic material — DNA and RNA — in place of gears or electrons. The team calls its biological transistor the “transcriptor."

“Transcriptors are the key component behind amplifying genetic logic — akin to the transistor and electronics,” said Jerome Bonnet, PhD, a postdoctoral scholar in bioengineering and the paper’s lead author.

The creation of the transcriptor allows engineers to compute inside living cells to record, for instance, when cells have been exposed to certain external stimuli or environmental factors, or even to turn on and off cell reproduction as needed.

“Biological computers can be used to study and reprogram living systems, monitor environments and improve cellular therapeutics,” said Drew Endy, PhD, assistant professor of bioengineering and the paper’s senior author.

In electronics, a transistor controls the flow of electrons along a circuit. Similarly, in biologics, a transcriptor controls the flow of a specific protein, RNA polymerase, as it travels along a strand of DNA.

“We have repurposed a group of natural proteins, called integrases, to realize digital control over the flow of RNA polymerase along DNA, which in turn allowed us to engineer amplifying genetic logic,” said Endy.

Using transcriptors, the team has created what are known in electrical engineering as logic gates that can derive true-false answers to virtually any biochemical question that might be posed within a cell.

They refer to their transcriptor-based logic gates as “Boolean Integrase Logic,” or “BIL gates” for short.

Transcriptor-based gates alone do not constitute a computer, but they are the third and final component of a biological computer that could operate within individual living cells.

Despite their outward differences, all modern computers, from ENIAC to Apple, share three basic functions: storing, transmitting and performing logical operations on information.

Last year, Endy and his team made news in delivering the other two core components of a fully functional genetic computer. The first was a type of rewritable digital data storage within DNA. They also developed a mechanism for transmitting genetic information from cell to cell, a sort of biological Internet.

It all adds up to creating a computer inside a living cell.

Digital logic is often referred to as “Boolean logic,” after George Boole, the mathematician who proposed the system in 1854. Today, Boolean logic typically takes the form of 1s and 0s within a computer. Answer true, gate open; answer false, gate closed. Open. Closed. On. Off. 1. 0. It’s that basic. But it turns out that with just these simple tools and ways of thinking you can accomplish quite a lot.

“AND” and “OR” are just two of the most basic Boolean logic gates. An “AND” gate, for instance, is “true” when both of its inputs are true — when “a” and “b” are true. An “OR” gate, on the other hand, is true when either or both of its inputs are true.

In a biological setting, the possibilities for logic are as limitless as in electronics, Bonnet explained. “You could test whether a given cell had been exposed to any number of external stimuli — the presence of glucose and caffeine, for instance. BIL gates would allow you to make that determination and to store that information so you could easily identify those which had been exposed and which had not,” he said.

By the same token, you could tell the cell to start or stop reproducing if certain factors were present. And, by coupling BIL gates with the team’s biological Internet, it is possible to communicate genetic information from cell to cell to orchestrate the behavior of a group of cells.

“The potential applications are limited only by the imagination of the researcher,” said co-author Monica Ortiz, a PhD candidate in bioengineering who demonstrated autonomous cell-to-cell communication of DNA encoding various BIL gates.

To create transcriptors and logic gates, the team used carefully calibrated combinations of enzymes — the integrases mentioned earlier — that control the flow of RNA polymerase along strands of DNA. If this were electronics, DNA is the wire and RNA polymerase is the electron.

“The choice of enzymes is important,” Bonnet said. “We have been careful to select enzymes that function in bacteria, fungi, plants and animals, so that bio-computers can be engineered within a variety of organisms.”

On the technical side, the transcriptor achieves a key similarity between the biological transistor and its semiconducting cousin: signal amplification.

With transcriptors, a very small change in the expression of an integrase can create a very large change in the expression of any two other genes.

To understand the importance of amplification, consider that the transistor was first conceived as a way to replace expensive, inefficient and unreliable vacuum tubes in the amplification of telephone signals for transcontinental phone calls. Electrical signals traveling along wires get weaker the farther they travel, but if you put an amplifier every so often along the way, you can relay the signal across a great distance. The same would hold in biological systems as signals get transmitted among a group of cells.

“It is a concept similar to transistor radios,” said Pakpoom Subsoontorn, a PhD candidate in bioengineering and co-author of the study who developed theoretical models to predict the behavior of BIL gates. “Relatively weak radio waves traveling through the air can get amplified into sound.”

To bring the age of the biological computer to a much speedier reality, Endy and his team have contributed all of BIL gates to the public domain so that others can immediately harness and improve upon the tools.

“Most of biotechnology has not yet been imagined, let alone made true. By freely sharing important basic tools everyone can work better together,” Bonnet said.

The research was funded by the National Science Foundation and the Townshend Lamarre Foundation.

Information about Stanford’s Department of Bioengineering, which also supported the work, is available at http://bioengineering.stanford.edu. The department is jointly operated by the School of Engineering and the School of Medicine.

Original story at Stanford Medicine website:
http://med.stanford.edu/ism/2013/march/bil-gates.html