Applying structural biology to drug discovery, for the most part, has meant NMR spectrometry or high-throughput X-ray crystallography (consider the buzz surrounding companies like Structural Genomix or Astex Technology for their work over the last several years elucidating the structures of promising drug targets). But now electron tomography, a relative upstart, is making a run at challenging the dominance of NMR and X-ray crystallography in big pharma research. Hans Johansson, the new CEO of Stockholm-based Sidec Technologies, thinks his company has the technical prowess to do it.
A spin-off from Sweden’s Karolinska Institute, four-year-old Sidec has its origins in the lab of Ulf Skoglund, a structural chemist in the department of cell and molecular biology. Electron tomography, which involves reconstructing a series of photographs taken by an electron microscope into a 3-D image, is a relatively well-defined tool, but Skoglund had the idea of applying some clever mathematics to boost the resolution of the 3-D images. Relying on a mathematical formulation developed in the 1950s known as constrained maximum entropy, Skoglund managed to reduce the noise associated with the 3-D images, thereby significantly improving their quality. In 1996 his group filed patents and published on their work in the Journal of Structural Biology. [Skoglund, U., Öfverstedt, L.-G., Burnett, R. and Bricogne, G. (1996). Maximum-entropy three-dimensional reconstruction with deconvolution of the contrast transfer function: a test application with adenovirus. Journal of Structural Biology, 117, 173-188.]
[Skoglund, U., Öfverstedt, L.-G., Burnett, R. and Bricogne, G. (1996). Maximum-entropy three-dimensional reconstruction with deconvolution of the contrast transfer function: a test application with adenovirus. Journal of Structural Biology, 117, 173-188.]
In 2000, Skoglund founded Sidec to commercialize his research with initial financing from the Karolinska Investment Fund and the Swedish Industrial Development Fund. The first couple years of the company’s existence involved scaling up the technology for industrial applications, says Johansson, who joined Sidec as CEO this past September. Now, Johansson, a chemical engineer by training with management experience at Biotage and Personal Chemistry, has plans to expand beyond the EU, where most of its 10 big pharma and biotech customers reside, and focus on breaking into the market for structural biology services in the US. Earlier this year, Sidec established a one-man outpost in San Diego.
Despite the challenges to convincing big pharma of the benefits to trying out a new technology, Johansson thinks he has a few selling points. Compared to X-ray crystallography, which requires that proteins under investigation be frozen in one configuration, electron tomography can generate images of proteins in situ, he says. Furthermore, electron tomography — unlike NMR — is not constrained by an upper limit on the size of proteins it can visualize, Johansson adds. “Our technology is more suited to studying interactions,” he says. “In that way we’re closer to what the cell biologists want.”
— John S. MacNeil