Membrane proteins are pretty awful molecules to work with. Unlike soluble proteins that often happily crystallise, the hydrophobic surfaces of membrane proteins make crystallisation a nightmare, and yet they are such important proteins for signal transduction and molecular transport that structural biologists are very keen to have a good look at them.

Only a handful of membrane protein structures have been elucidated, mainly using cryoelectron microscopy; the rest remain in the great unknown. While some researchers continue to refine X-ray crystallography techniques and electron microscopy to hunt down and uncover these recalcitrant molecules, others are looking at different approaches to the problem.

Possibly the most promising approach is to use coherent X-ray diffraction from single molecules. This technique is similar to X-ray crystallography in that a diffraction pattern is measured, however it has a major benefit - there is no need to crystallise the proteins. Instead, a coherent beam of x-rays - a targeted beam, like a laser - is shone at a single object and its diffraction pattern is measured.

At the ARC Centre of Excellence for Coherent X-ray Science (CXS), researchers have already used the technique to obtain images of cells and are working their way towards individual molecules. For example, biochemist Professor Leann Tilley from La Trobe University, who is also Deputy Director of CXS, has tested the technique on malaria parasite-infected red blood cells and come up with the goods.

"With higher and higher intensity sources, you may be able to get the structures of individual proteins just from their individual diffraction patterns," Tilley says. "The holy grail is to get molecular information about cell components without taking them out of that cellular environment. That is the promise of x-rays."

Tilley's colleague at La Trobe and leader of the Biological Sciences Program at CXS, Associate Professor Mike Ryan, is working on mitochondrial diseases and is particularly interested in some of the membrane proteins involved in disease processes. He too is interested in whether coherent diffraction imaging can give him structural information about essential membrane proteins without having to crystallise them.