University of California, Los Angeles

This project will develop tools having the potential to better understand cells in health and disease by providing precise pictures of the interacting molecules. Nano X-ray diffraction can reveal the 3D atomic structure of intracellular organelles and aggregates that mediate the metabolism and pathology of cells. In contrast, nearly all present information on the atomic structure of cellular constituents has come from purified molecules, removed from cells. The research group will exploit recent advances in the production of highly focused (nano) X-ray beams and free electron lasers, directing these beams onto biological cells and subcellular organelles, prepared by new methods for X-ray examination, and devise methods for collecting and interpreting the diffraction data. One application will be to learn the atomic structure of the carboxysome, the organelle that removes CO2 from the atmosphere, a process that is critical to sustaining life on earth as we know it. A second application will be to learn which types of cells contain aggregates of protein in the amyloid state, a state similar to the deposits formed in Alzheimer’s and Parkinson’s diseases, but in some cases apparently part of normal function. The same tools will be applied to microcrystals and microdomains of larger crystals with the potential to gain significantly more information than is presently possible.