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sabato 11 luglio 2015

Designer Bacteria

This illustration shows Bacteroides thetaiotaomicron (white) living on cells in the gut (large pink spheres) and being activated by chemical signals (small green dots) to express specific genes. The glowing bacteria are encoding light-generating proteins (Janet Iwasa)

UNO DEI BATTERI più comuni nell'intestino umano è stato riprogrammato geneticamente e dotato di sensori, circuiti e memorie artificiali che potranno essere usati per diagnosticare e curare 'in loco' patologie come il tumore del colon o le malattie infiammatorie intestinali. 

Questo risultato, pubblicato sulla rivista Cell Systems, porta la firma degli esperti di biologia sintetica del Massachusetts Institute of Technology (Mit) di Boston.

Il microrganismo riprogrammato si chiama "Bacteroides thetaiotaomicron" ed è un batterio 'buono' che vive stabilmente nell'intestino dell'uomo dove forma colonie molto numerose. 

La sua versione '2.0' è stata ottenuta manipolando il Dna con tecniche avanzate di biologia sintetica. In questo modo il microrganismo è stato dotato di strumenti innovativi come le memorie genetiche, che 'ricordano' i cibi ingeriti, e nuovi geni 'sensori', che si accendono o spengono in risposta a stimoli esterni (ad esempio il sanguinamento  intestinale). 

Una volta trasferito nell'intestino di topo, il batterio modificato si è replicato e ha formato nuove colonie capaci di 'ricordare' quello che l'animale mangiava. Un risultato importante, che apre la strada alla programmazione del microbioma intestinale

Researchers are still studying exactly how the microbiome — the billions of bacteria and other tiny critters that inhabit our bodies — impacts human health. 

But while they get on with that, engineers are assembling a tool kit that could build designer microbes: specially tailored bacteria that doctors could introduce into the microbiome to diagnose, monitor or even treat disease.

This week, a team at MIT said it had taken a step toward that goal by building tools that can program a common, helpful intestinal bacterium known as Bacteroides thetaiotaomicron. The group inserted custom DNA components into the microbe's genome much as software engineers insert code into an app, and then showed in mice that the genetic parts worked.

"Just as you'd program computers, we're starting to learn how to program cells by modifying their DNA," said Timothy Lu, a biological and electrical engineer at MIT and senior author of a study detailing the Bacteroides experiment, published Thursday in the journal Cell Systems.

Bacteroides thetaiotaomicron is present in large numbers in many people — 46% of us have it in our digestive tracts, according to background provided in the study.  Additionally, it and other Bacteroides species are very stable in the intestines, the authors wrote, making them particularly useful for medical treatments.

"If you're thinking of making a therapy, it's going to be useful to work in an organism that's there in the gut in large numbers," Lu said.

But while Bacteroides is everywhere, it hasn't been studied as widely as less-abundant bacteria like E. coli, for which scientists already have written many genetic components, Lu said.  That's because researchers only recently realized how important Bacteroides is for gut function and because it's trickier to cultivate in the lab.

Hoping to jump-start the work, Lu and MIT colleague Christopher Voigt led a team that designed several DNA-based components to control genes in Bacteroides. They built sensors, memory and circuits that allowed them to switch on and off special light-emitting genes they had introduced into the microbes. They used a gene-editing tool known as CRISPR to target two genes that were native to Bacteroides and switch them on and off as well.

To show that their tool kit had the potential to work as a therapy, the scientists administered the bacteria to laboratory mice and examined the animals' droppings for glowing and for DNA signals that would indicate that the tools functioned in the rodents.

By and large, the components worked, hinting that engineers might soon be able to craft Bacteroides organisms that might be able to live alongside their cousins in the human gut and help treat disease.

Lu said such bacteria could be useful for noninvasive diagnostics — sensing, for instance, when a patient with inflammatory bowel disease is about to have a flare up. It also might be possible to design a microbe that could administer drugs on an as-needed basis. But before the technology could be tested in people, he added, engineers would want to create and fine-tune Bacteroides sensors to detect inflammation, bleeding, cancers and the other conditions they hope to target. They'd also have to conduct animal trials.

Designer bacteria might also be useful in other parts of the body, such as the mouth, the skin or the female genital tract.

"Bacteria live everywhere," Lu said, adding that advances in gene editing are making it easier for engineers to construct genetic tool kits like this one.

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