WORLDS LARGEST DNA ORIGAMI CREATED

Researchers from North Carolina State University, Duke University and the University of Copenhagen have created the world's largest DNA origami, which are nanoscale constructions with applications ranging from biomedical research to nanoelectronics

"These origami can be customized for use in everything from studying cell behavior to creating templates for the nanofabrication of electronic components," says Dr. Thom LaBean, an associate professor of materials science and engineering at NC State and senior author of a paper describing the work.

DNA origami are self-assembling biochemical structures that are made up of two types of DNA. To make DNA origami, researchers begin with a biologically derived strand of DNA called the scaffold strand. The researchers then design customized synthetic strands of DNA, called staple strands. Each staple strand is made up of a specific sequence of bases (adenine, cytosine, thaline and guanine -- the building blocks of DNA), which is designed to pair with specific subsequences on the scaffold strand.

The staple strands are introduced into a solution containing the scaffold strand, and the solution is then heated and cooled. During this process, each staple strand attaches to specific sections of the scaffold strand, pulling those sections together and folding the scaffold strand into a specific shape.

The standard for DNA origami has long been limited to a scaffold strand that is made up of 7,249 bases, creating structures that measure roughly 70 nanometers (nm) by 90 nm, though the shapes may vary.

However, the research team led by LaBean has now created DNA origami consisting of 51,466 bases, measuring approximately 200 nm by 300 nm.

"We had to do two things to make this viable," says Dr. Alexandria Marchi, lead author of the paper and a postdoctoral researcher at Duke. "First we had to develop a custom scaffold strand that contained 51 kilobases. We did that with the help of molecular biologist Stanley Brown at the University of Copenhagen.

"Second, in order to make this economically feasible, we had to find a cost-effective way of synthesizing staple strands -- because we went from needing 220 staple strands to needing more than 1,600," Marchi says.

The researchers did this by using what is essentially a converted inkjet printer to synthesize DNA directly onto a plastic chip.

"The technique we used not only creates large DNA origami, but has a fairly uniform output," LaBean says. "More than 90 percent of the origami are self-assembling properly."

The research was supported by the National Science Foundation under grants CDI-0835794, OISE-1246799, and EPMD-1231888, and by the University of Copenhagen.

DESIGNER BARREL PROTEINS CREATED

Proteins are long linear molecules that fold up to form well-defined 3D shapes. These 3D molecular architectures are essential for biological functions such as the elasticity of skin, the digestion of food, and the transport of oxygen in blood.

Despite the wide variety of tasks that natural proteins perform, they appear to use only a limited number of structural types, perhaps just a few thousand or so. These are used over and over again, being altered and embellished through evolution to generate many different functions. This raises the question: are more protein structures possible than those used and presented to us by nature?

A team from Bristol's School of Chemistry and School of Biochemistry, headed by Professor Dek Woolfson, have addressed this by designing humanmade protein molecules from scratch.

Although the design principles used are learned from natural proteins, from which the team develops rules for assembling their proteins, some of the designed protein shapes are completely new and have not been observed in nature yet.

Specifically, the scientists have made proteins with central cavities, or channels, running through them. The team believes that these will be useful in designing new protein functions, such as catalysts for breaking down fats, or molecules that span cell membranes to allow new communications between cells.

Professor Woolfson said: "This is a really exciting time to be exploring what can be done with biological principles and building blocks to make new and useful molecules, but completely outside the context of biology itself. It is one aspect of the emerging field of synthetic biology, in which Bristol is taking a lead both nationally and internationally."

This work has been highly collaborative combining computational modelling, peptide chemistry, biophysics and protein X-ray crystallography across the Schools of Chemistry (Drew Thomson, Antony Burton, Gail Bartlett and Dek Woolfson) and Biochemistry (Richard Sessions and Leo Brady), and an South West Doctoral Training Partnership student (Chris Wood) working between the two Schools.