September 16, 2023 pendari1090

Why Time-Resolved Cryo-EM?

 

Investigating the three-dimensional (3D) shapes of molecules such as proteins and nucleic acids enables us to understand their biological function, how therapeutic drugs interact with their targets, and how mutations may give rise to disease. A technology called cryo-electron microscopy (cryo-EM) enables us to do this through imaging biological molecules with electrons and reconstructing their 3D shapes and structures from the images. How we prepare molecules for cryo-EM is very slow compared to the rate at which they function in our bodies. Therefore, it is challenging to understand how molecules change their 3D architecture on the rapid timescales that they function with current cryo-EM technology. 

To overcome this barrier, we developed technology for time-resolved cryo-EM that we call cryo-EM Sample Preparation with light-Activated Molecules (C-SPAM). C-SPAM enables us to capture biological events for cryo-EM on very rapid timescales. Thus, we can use C-SPAM to understand how molecules change their shapes to function on the timescales that this occurs in our cells. Importantly, we will apply C-SPAM to investigate how drug candidates alter molecules on clinically-relevant timescales.

Our C-SPAM technology is fully open-source and open-access for the community. You can find more details here:

https://www.biorxiv.org/content/10.1101/2023.08.24.554704v1