DNA transistors

Several media outlets have been reporting on the topic of DNA transistors, which use genetic material as a type of switch inside of a cell. NPR has a pretty good description of the project and a link to a YouTube video:

Transistors are simple on/off switches. Computers are made of many millions of these switches. And to program a cell, you need a biological version. As Endy reports this week in Science, he managed to make one out of DNA.

His switch, which he calls a “transcriptor,” is a piece of DNA that he can flip on and off, using chemicals called enzymes. Endy put several of these DNA switches inside his bacteria. He could use the switches to build logic circuits that program each cell’s behavior. For example, he could tell a cell to change color in the presence of both enzyme A and enzyme B. That’s a simple program: IF enzyme A AND enzyme B [are present] THEN turn green. For an in-depth look, check out Endy’s own explanation on YouTube.

There is also the following graphical explanation:

The enzymes turn on the switch and allow the transcription of a DNA sequence into RNA. This transcription will then lead to some observable cellular phenomenon.

The research appears in Science.

DNA from HeLa cells is sequenced

HeLa cells viewed under a light microscope

Nature magazine reports that a German lab has sequenced the DNA of HeLa cells. Like cells from most tumors, there are multiple copies of many genes. Excerpt:

Previous work showed that HeLa cells, like many tumors, have bizarre, error-filled genomes, with one or more extra copies of many chromosomes. To get a closer look at these alterations, a team led by Lars Steinmetz, a geneticist at the EuropeanMolecular Biology Laboratory in Heidelberg, Germany, sequenced the popular ‘Kyoto’ version of the cell line and compared the sequence with that of a reference human genome. The team’s results are published in G3.

Steinmetz’s team confirmed that HeLa cells contain one extra version of most chromosomes, with up to five copies of some. Many genes were duplicated even more extensively, with four, five or six copies sometimes present, instead of the usual two.  Furthermore, large segments of chromosome 11 and several other chromosomes were reshuffled like a deck of cards, drastically altering the arrangement of the genes.

Without the genome sequence of Lacks’ healthy cells or that of her original tumor, it is difficult to trace the origin of these alterations. Steinmetz points out that other cervical tumors have massive rearrangements on chromosome 11, so the changes in the HeLa cell may have contributed to Lacks’ tumor.

HeLa cells have been the subject of many biological studies as they are easy to culture and replicate very fast. The cells were originally isolated from an African American woman named Henrietta Lacks, and have been cultured for over 60 years. There is also a fascinating book about the origin of these cells called The Immortal Life of Henrietta Lacks.

strawberry dna

Strawberries

If you have kids and have some time to spare this weekend try this fun science experiment from Scientific American, extracting DNA from strawberries.

dna data storage

DNA, RNA and their bases

In the January 23rd edition of Nature a team of scientists report using DNA to store poems, a picture and a recorded speech. From Science News:

Led by Nick Goldman, researchers from the European Bioinformatics Institute in England began by converting the five files into bits (technically, “trits” — they used a triplet code comprising zero, one and two). Then they translated that code into one made of As, Cs, Gs and Ts, the “letters” of DNA. So TAGAT replaces the “T” that begins line two of Shakespeare’s sonnet 18: “Thou art more lovely and more temperate.”  The team also incorporated a way to index the data — sort of a DNA version of the Dewey Decimal System — and an error correction code to keep the data clean.

Then the researchers sent their code to the instrumentation company Agilent Technologies in Santa Clara, Calif. There scientists read the code and used it to build millions upon millions of DNA molecules, which they sent back to the researchers via FedEx in a test tube inside a cardboard box.

When the test tube, about the size of a pinkie finger, arrived, Goldman and his colleagues sequenced the DNA, the same way researchers read the DNA of organisms, reconstructing the original files. The translation from data to DNA and back was free of errors, says Goldman.

DNA storage offers the potential of holding vastly more data in a smaller amount of space. It might also potentially be cheaper as the cost of DNA synthesis and sequencing continues to become less costly.

"junk" dna not so junky

Junk DNA

From the New York Times:

The human genome is packed with at least four million gene switches that reside in bits of DNA that once were dismissed as “junk” but that turn out to play critical roles in controlling how cells, organs and other tissues behave. The discovery, considered a major medical and scientific breakthrough, has enormous implications for human health because many complex diseases appear to be caused by tiny changes in hundreds of gene switches.

The findings are the fruit of an immense federal project, involving 440 scientists from 32 labs around the world. As they delved into the “junk” — parts of the DNA that are not actual genes containing instructions for proteins — they discovered it is not junk at all. At least 80 percent of it is active and needed.

The result is an annotated road map of much of this DNA, noting what it is doing and how. It includes the system of switches that, acting like dimmer switches for lights, control which genes are used in a cell and when they are used, and determine, for instance, whether a cell becomes a liver cell or a neuron.

More here.

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.

cloning a woolly mammoth

Its a story straight out of Jurassic Park! But for some reason, I’m highly doubtful that this will work.

Mammoth remains were uncovered in thawed Siberian permafrost, and scientists around the world have been trying to extract DNA from the remains. Previously, paleobiologists were able to reproduce mammoth blood protein, and Japanese researchers want to resurrect the mammoth within five years. This new project will move forward if the Russian institution, the North-Eastern Federal University of the Sakha Republic, can ship its mammoth remains to the Koreans.

[…]

The plan would work like previous cloning studies that successfully reproduced dogs, a cow, a cat, a pig, a wolf and coyotes. The nuclei of mammoth somatic cells would be implanted into the nuclei of donor elephant eggs, to produce elephant embryos with mammoth DNA. The embryos would then be implanted in elephant wombs, where they would gestate for 22 months. The team plans to use an Indian elephant for the cell nucleus transfer, according to AFP.

But I guess it’s worth a shot. What can go wrong, right? (Everything.) But how cool would a modern woolly mammoth be?

[Source] Popular Science

Aside: The researcher in charge of this project, Hwang Woo-suk, is quite controversial. He previously claimed to have cloned a human embryo and used the clone to generate stem cells. But his methods for obtaining the embryo was later called into question and his results turned out to have been falsified. He served a sentence for embezzlement and bioethics violations for his actions.