This project aims to further develop the method of femtosecond nanocrystallography for the structure determination of membrane proteins. Membrane proteins have an overwhelming impact on human health; over 30% of human genes code for membrane proteins and 60% of all drugs target these proteins. Femtosecond crystallography is a new method for X-ray structure analysis of biological macromolecules, where hundreds of thousands of X-ray diffraction snapshots are collected from a stream of fully hydrated nano/microcrystals of proteins, using femtosecond X-ray pulses from a Free Electron Laser. The peak flux of an X-ray FEL is 109 times higher than the flux from a 3rd generation Synchrotron. While the X-ray pulses are so strong that they destroy any solid material, X-ray diffraction occurs before the biomolecules are destroyed. New developments in nanocrystal growth and characterization, together with development of new injector technology and data evaluation methods have progressed the new method of SFX at a very fast pace based on results from this project which has led to 16 publications, 9 of them in Nature of Science journals. The proposal is focused on four major aims which include the development of new methods for nanocrystal growth and characterization (aim 1), innovations on new crystal sorting and Injector technology (aim 2), further development of data analysis methods including de novo phasing of SFX data (aim 3) and determination of membrane protein structures with SFX and new avenues for time-resolved SFX (aim 4). The goal is to open a new era in Structural Biology, where SFX is developed and used to solve challenging membrane protein structures. The development of time resolved SFX will provide new milestones towards the final goal to determine molecular movies of membrane proteins in action.
|Effective start/end date||6/1/15 → 5/31/20|
- HHS-NIH: National Institute of General Medical Sciences (NIGMS): $1,465,922.00