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08.29.2012

using HIV to fight cancer

A model of HIV.

HIV, like other viruses, mutates rapidly in response to changes in its environment. This ability to rapidly change gives them the ability to evade the natural defense mechanisms our bodies trigger once we are infected. Researchers have found a way to exploit this property of HIV to generate proteins that will help fight cancer. From Popular Science:

As HIV replicates, it creates slightly new versions of itself over successive generations – this allows it to readily resist most of the drug cocktails and anti-viral treatments developed to fight it. But it could also allow HIV to serve as a sort of molecule factory, creating new iterations of compounds that work in slightly different ways.

The CNRS team modified the genome of HIV by inserting a human gene for a protein called deoxycytidine kinase (dCK). This protein is found in all cells and is important for activating anti-cancer drugs. Researchers would like to make a more potent form of dCK that would allow cancer drugs to work more effectively, which could in turn require less of them, causing fewer side effects and less toxicity.

The team multiplied this mutant HIV through several generations, yielding an entire library of mutant dCK proteins, about 80 in all. Ultimately, they found a variant that induces tumor cells to die. With just 1/300th the dose of cancer-killing drugs, this one-two protein punch is just as effective at stopping tumor growth.

For more read here. For the original research paper from PLoS Genetics go here.

04.20.2012

DNA, RNA, XNA

A DNA helix

DNA & RNA genetic information to be stored and propagated through the generations. Now researchers have created new molecules called XNAs by replacing the sugar molecules on the DNA or RNA phosphate backbone with an analog. From Science News:

The researchers, led by Philipp Holliger of the MRC Laboratory of Molecular Biology in Cambridge, England, did make completely new genetic molecules. In the backbone of every DNA molecule there are repeating units of deoxyribose sugar, in the RNA backbone it’s ribose sugar. Instead of those sugars, the various XNAs have different molecules in their backbones: a five-carbon sugar called arabinose in ANA, the ringed structure anhydrohexitol in HNA, and threose, a four-carbon sugar in TNA. The scientists also created XNA molecules called FANA (2´-fluoroarabinose), CeNA (cyclohexene) and LNA (“locked” ribose analog).

In a second bioengineering feat, the researchers created special enzymes for the XNAs so that they could evolve. This requires enzymes that can “read” the order of molecular components in a strand of XNA and use that information to build a complementary strand of DNA. Working with an enzyme from a sulfur-loving microbe, the team selected for versions that could “read” each of the XNAs. The researchers also made enzymes that could do the reverse: read DNA and use that information to build XNA.

Because the XNAs can’t copy themselves without help from DNA, it’s not truly synthetic life, says Joyce. But the molecules do undergo good old-fashioned evolution. With HNA, for example, the researchers created a random population of HNA molecules, then exposed them to a bunch of target molecules (such as proteins or RNA) for the HNA to attach to. Most of the HNAs didn’t do diddly-squat, but a fraction were slightly better at connecting to the target molecules.

More here and here.

04.12.2012

resistant bacteria are as old as time

Inside the Lechuguilla cave

Antibiotic resistant bacteria are an increasing threat to our health care system. Because antibiotics are over-prescribed and also administered to livestock in their feed, bacteria have developed mechanisms to withstand antimicrobial drugs. As bacteria evolve to evade current antibiotics they become harder and harder to treat. While this may appear to be a problem created by modern medicine, there is evidence that the ability to develop drug resistance mechanisms is hard wired in bacteria. A group of scientist have uncovered species of drug resistant bacteria in a 4 million year old cave. From Scientific American:

But the capacity to fend off antibiotics might actually be lodged deep in bacteria’s evolutionary history. A new study has uncovered dozens of species of bacteria in a 4 million-year-old cave that harbor resistance to both natural and synthetic antibiotics.

A team of researchers descended to 400 meters in distant, untrafficked reaches of Lechuguilla Cave in New Mexico to collect samples of bacteria. Few people have entered the cave’s deepest regions since its discovery in 1986, and surface water takes thousands of years to percolate through the nearby dense Yates Formation rock down to the cave. As a consequence, the area is a prime place to study naturally occurring antibiotic resistance, noted the researchers, whose results were published online April 11 in PLoS ONE.

…

Wright and his colleagues found that of the 93 bacterial strains tested from the cave, most were resistant to more than one of the 26 different antimicrobials. And some bacteria were resistant to more than a dozen antibiotics used by doctors, such as telithromycin, ampicillin and daptomycin, which is currently a treatment of last resort to combat resistant infections. The cave bacteria were not likely to cause infection in humans, but could provide the genetic traits that confer resistance to that are.

Check out the research article on PLoS ONE.

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