Students from Cambridge University, in England, engineered bacteria to produce pigments in all colors of the rainbow (shown above) as part of the International Genetically Engineered Machines Competition at MIT. Credit: Mike Davies

Bioengineering students from around the world converged on MIT this weekend in what has become an annual ritual in synthetic biology--iGEM, the international genetically engineered machines competition. Among the finalists this year were "GluColi", a new generation of glue made by bacteria, a biological version of an LCD screen made of yeast, and a multicolored menagerie of bacteria that might ultimately become part of a biological system designed to change color in response to toxins or other target compounds, providing an easy-to-read warning system.

By combining snippets of DNA, dubbed biological "parts", students build microbes designed to perform useful functions, such as producing medicines or detecting toxins. Each year "parts" built for the competition are entered into a biological library, so that next year's teams can use them to build even more sophisticated machines. As iGEM co-founder and MIT bioengineer Tom Knight explained in a previous piece, "The key idea here is to develop a library of composable parts which we think of in the same way as Lego blocks. These parts can be assembled into more-complex pieces, which in many cases are functional when inserted into living cells."

Entries into previous years have included yeast designed to produce beer with the health benefits of red wine, sweet-smelling E. coli, a commonly used research bacterium with a vile odor, and probiotic bacteria, like that found in yogurt, designed to fight cavities, produce vitamins, and treat lactose intolerance.

To make multicolored microbes, students from Cambridge University, in England, mined bacterial genomes for pigment-producing genes. They then engineered those genes into the harmless strain of E. coli used in genetic research. Carotinoid enzymes co-opted from Pantoea ananatis, a bacterium that can rot onions, generated red and orange pigments. A gene for melanin, an enzyme from the soil bacterium Rhizobium etli, produces brown. Chromobacterium violacein, a soil and water dwelling microbe offered genes capable of producing shades of violet, green and blue.

After five challenging years of searching, Hugh Rienhoff might be near the end of his quest. The bio-entrepreneur, a clinical geneticist by training, is trying to find the cause of an unusual collection of symptoms in his daughter Beatrice, including muscle weakness, curled fingers, and long limbs. About a year ago, Illumina, a California-based genomics company, sequenced parts Beatric's genome, along with that of Rienhoff and his wife. The determined father has spent the last twelve months searching through the data for mutations that only Beatrice possesses.

Her symptoms resemble those of a collection of rare genetic disorders, including Marfan's syndrome, a condition that leads to defective connective tissue and serious heart problems. So far, Beatrice doesn't have any of the mutations known to cause those diseases, and her heart looks healthy. But that has done little to assuage her father's worry. "My primary concern is that she is at risk for vascular disease," he says.

Rienhoff has focused his search on genes involved in the molecular pathway of transforming growth factor beta (TGF-β), a molecule that provides a common thread between different disorders with symptoms resembling Beatrice's. The protein is involved in different aspects of development, including that of smooth muscle. (Prior to the Illumina sequencing, Rienhoff had been doing his own genomic analysis. He bought equipment for amplifying DNA and began isolating genes involved in the TGF-beta molecular pathway from his daughter's blood, sending them out to be sequenced.)

With the help of Vincent Butty, a scientist at MIT, Rienhoff has compiled a list of genetic variations in Beatrice's genome, filtering out those found in both his and his wife's genomes. He is working on the assumption that the genetic culprit arose anew in Beatrice's DNA and would therefore be absent in her parents. Rienhoff and Butty presented the latest findings from their search at the Personal Genomes conference in Cold Spring Harbor this week--so far, they have identified approximately 80 genes that less active in Beatrice than her parents.

One of the biggest challenges, Rienhoff says, is the software available to analyze the data. "To ask the questions I want to ask would take an army," he says. "I'm trying to connect the dots between being a genomicist and a clinical geneticist. I don't think anyone here realizes how difficult that is. I'm willing to take it on because it matters to me."

Fortunately, Rienhoff has new help in his personal hunt. He sent the sequence information to George Church last week, a Harvard geneticist who heads the Personal Genomics Project. And Reinhart says he has now been approached by sequencing companies offering to do the families entire genome.

"I think there is a message--studying rare diseases is informative of common diseases," says Rienhoff. "If we look at the numbers of disorders related to TGF-beta and Marfan syndrome, we might be able to explain a good percentage of aortic aneurisms. The same drug that helps Marfan might help them."

According to a blog at Nature.com, Illumina plans to expand the sequencing project.

Because Illumina sequences from mRNA transcripts, Vincent Butty of the Massachusetts Institute of Technology -- who's been analyzing the data -- has been able to see direct relationships between the sequence of the genes and their expression levels. For example, he found a variant of CPNE-1 with a single base pair change. Both Rienhoff and his wife have one normal copy of the gene and one copy of the variant, but Beatrice inherited both copies of the variant, and her expression of the gene is drastically reduced compared to her parents. It's not clear yet if the variant is responsible for her condition, however, and there are many other leads to follow in the data.

Nevertheless, Illumina plans to perform this style of transcriptome profiling on up to nine more family trios, five of whom have children that have been diagnosed with Loyes Dietz syndrome, and four others with a variety of clinical presentations including autism, developmental delays and congenital heart failure.

Tiny, triangular DNA structures self-assemble on silicon. Credit: IBM

Artificial, self-assembling DNA structures may help make smaller and cheaper microchips, according to research presented in the latest issue of Nature Nanotechnology. Tinier microchips would allow faster computers and other electronics.

Researchers from IBM and the California Institute of Technology used a technique known as DNA origami, where a long strand of DNA is folded into a shape with many shorter strands dubbed staples, creating a three-dimensional shape. In the paper, the researchers demonstrated using DNA origami-shapes as a scaffold for carbon nanotubes--a trick that could eventually be used to create nanoscale microchips.

The DNA structures are tiny enough to have features measuring six nanometers--the current industry standard for microchips is 45 nanometers. The process could replace the expensive tools manufacturers currently use to make tiny chips, although IBM suggests that it could take up to 10 years to test and refine the process for manufacturing.