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SoCoBio Student Publication: Jack Stubbs – Small but mighty: the power of microcrystals in structural biology

Scientists are making remarkable strides in structural biology by harnessing the power of microcrystals to study the intricate dynamics of biological molecules. Thanks to cutting-edge advancements, researchers can now analyse these structures with unprecedented detail using specialized techniques such as microcrystal electron diffraction (MicroED) and room-temperature (RT) crystallography.

Traditionally, structural studies required relatively large crystals, but improvements in X-ray sources and microfocus beamlines have enabled scientists to work with much smaller ones. This breakthrough is particularly valuable for samples that are difficult to crystallize, expanding the scope of structural investigations.

MicroED provides atomic-level insights into molecular structures, while RT crystallography combined with serial crystallography, allows researchers to observe molecules in their natural physiological states. However, preparing microcrystals remains a challenge, as there is no universal approach that works for all samples. Developing reliable techniques for generating and handling these tiny crystals is essential for obtaining high-quality data.

Another crucial factor is sample delivery; efficiently delivering microcrystals to the X-ray beam. Optimizing these methods will enhance the potential of techniques like time-resolved (TR) crystallography, which captures molecular movements in real time. Such advancements are not only deepening our understanding of biological processes but also paving the way for new breakthroughs in medicine and drug discovery.

A recent review paper, co-authored by Jack Stubbs (University of Southampton & Diamond Light Source, 4th Year SoCoBio Industry Co-funded PhD student) and Courtney Tremlett (University of Exeter, 4th Year SWBio DTP PhD student), explores methods for matching microcrystal preparation with sample delivery strategies. The review emphasizes the importance of establishing robust protocols to further unlock the potential of microcrystals in structural biology.

The research has been published in the International Union of Crystallography Journal
https://doi.org/10.1107/S2052252525001484
For more information, please contact Jack Stubbs (jrs1u21@soton.ac.uk).