Thursday, September 28, 2023
9/28/2023
Project Summary This proposal aims to bring revolutionary next generation x-ray detector technology to the field of X-ray Free Electron Laser (FEL) based structural biology. X-ray FELs produce extremely short pulses of x-rays which can be exploited to obtain unique information about the structure and the dynamics of biological systems. These short bursts of x-rays allow data to be collected prior to the onset of radiation damage, resulting in higher resolution structural information compared to more traditional measurements. Additionally, the ultrashort pulses are ideal to study fast dynamics. Combined with data collection under ambient conditions, recently developed X-ray FEL methods of femtosecond crystallography provide unique capabilities to study biological dynamics under physiologically relevant conditions with high spatial and temporal resolution. Over the last 10 years the technique of femtosecond crystallography has evolved from its first demonstration in 2011 to a very useful tool for structural biology. Even though the field of femtosecond crystallography using FEL sources is still young, the detector technology has rapidly evolved since the start of operations of the Linac Coherent Light Source (LCLS). The detector system currently used at the Macromolecular Femtosecond Crystallography (MFX) instrument – the flagship instrument for bioscience research at LCLS – is significantly outdated and in great need of modernization. A large worldwide effort to develop new detector technology has produced paradigm-changing capabilities that are now available for scientific use. High dynamic range, fast (>2 kHz) detectors with single photon sensitivity and very low noise are now available. Such detectors are specifically designed for ultrashort pulses from X-ray FELs and can maximize the information collected from the single shots necessary for data collection prior to the onset of radiation damage. This proposal is to purchase a recently available Jungfrau 15M detector which will surpass by more than a factor of five the repetition rate and the dynamic range of the detector currently used for serial femtosecond crystallography at the MFX instrument at LCLS, while reducing the noise level. This will greatly improve the performance of LCLS femtosecond crystallography, allowing more access to the facility by providing higher quality data faster. It will also enable fundamentally new capabilities by allowing ever more challenging biological problems to be solved at LCLS. This detector will keep MFX instrument at LCLS at the forefront of X-ray FEL biology by continuing to provide a world-leading tool for solving uniquely challenging biological problems that conventional methods cannot solve. This will benefit important areas of biomedical research such as metallo- enzymes, membrane proteins, GPCRs and large protein complexes, as well as generally provide more broadly accessible capabilities to study the dynamics of biomolecules.
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