Xiaodong Zou, Photo: Yi Luo/Stockholms universitet
Xiaodong Zou, Photo: Yi Luo/Stockholms universitet

 

Detailed examination of the biomolecule structure enables scientists to understand the biomolecules functions and chemical processes in biological systems. The information is also important in the design of new drugs. Ever more advanced structure determination techniques have revolutionized biology and life sciences. However, each new technique also has its limitations.

The most frequently used method – X-ray crystallography – gives the position of every atom in a substance, but it requires the sample to be presented in the form of fairly large crystals. This is challenging, particularly when analyzing biological macromolecules – giant molecules with thousands of atoms. These include proteins found in the human body, responsible for driving nearly all biological processes. Cryo-electron microscopy is another method, which works well for studying large protein molecules and viruses, but less well for smaller molecules.

An alternative approach to these two methods has been microcrystal electron diffraction (MicroED), which can study crystals that are 100 million times smaller than required for X-ray diffraction. Zou’s research group has also been internationally leading in the development of MicroED methods and successfully applied them for determination of more than 100 unknown inorganic and organic structures.

“With electron diffraction, we can now study crystals that are 100 million times smaller than those used in X-ray crystallography and it can be used in many areas, for example to study organic molecules including, among other things, medicines. Therefore, it is an important area to explore further", says Xiaodong Zou, professor of structural chemistry at Stockholm University and new Wallenberg Scholar.

“So far, I have researched inorganic chemistry and material chemistry. Getting a Wallenberg Scholar grant means that I can branch out to a new research area and develop and use electron crystallography for biomolecules, a dream I have had since I was a doctoral student 30 years ago", says Xiaodong Zou.

“We were among the first in the world to develop quantitative methods for electron diffraction, and in recent years there has been some spectacular developments. Now there are computer-controlled electron microscopes and extremely fast and precise cameras", says Xiaodong Zou

Structural determination with the help of electron diffraction has received a lot of attention in recent years and was appointed by the journal Science to "one of the ten breakthroughs of 2018".

Xiaodong Zou will now take on the challenge of developing MicroED to study protein structures. In addition, she will evaluate how well the technology works for determining the charge states in important biological macromolecules. The goal is to establish MicroED as a method that can give faster results and is readily available to Swedish researchers.

“The aim of our research project is to develop both new methods and software for data collection and structural determination. The project's long-term goal is to make MicroED an equally fast, feasible and precise technique as todays X-ray crystallography", Xiaodong Zou says.

 

About the Wallenberg Scholar Programme

The aim of the programme is for the researchers to be able to adopt a long-term approach to their work, with less time and effort expended on seeking external funding, and with higher ambitions, so that their research has an even greater international impact. The grants also enable researchers to commit to more challenging and longer-term projects.

The Knut and Alice Wallenberg Foundation awards grants to Wallenberg Scholars in the fields of medicine, science and technology. The Marianne and Marcus Wallenberg Foundation and the Marcus and Amalia Wallenberg Foundation award grants to Wallenberg Scholars in the social sciences and humanities.

Following this year’s grant awards, there are 63 active Wallenberg Scholars. The next cohort of Wallenberg Scholars will be chosen in 2023.