The Center for Applied Structural Discovery (CASD) is a core member of the Biodesign Institute at Arizona State University. Its research complements the institute’s mission to overcome complex global challenges by unlocking life’s important secrets to create knowledge for improving human health, security and sustainability.
CASD is actively involved in the following research projects:
Femtosecond Nano-Crystallography of Membrane Proteins (NIH, NIGMS)
Femtosecond pulses of X-ray free electron lasers are used to investigate the structure of membrane proteins. The project aims to develop the method of femtosecond crystallography for the structure determination of membrane proteins, where X-ray structure analysis is based on hundreds of thousands of X-ray diffraction patterns from a stream of fully hydrated nano/microcrystals of membrane protein crystals. The determination of membrane proteins structures solved to date often involves a long process where it took years (or sometimes even decades) to grow large, well-ordered crystals suitable for X-ray structure determination. Furthermore, X-ray damage is a major problem for many membrane protein crystals, especially when they contain redox active cofactors, and it also imposes a limitation for X-ray diffraction on microcrystals, even under cryogenic conditions. This project aims to open an exciting new avenue for membrane protein crystallography, where hundreds of thousands of diffraction patterns can be collected in a few minutes from fully hydrated micro/nano crystals in their native conditions at room temperature, using X-ray laser pulses that are so short that no X-ray damage occurs during data collection. This method will be used to solve novel X-ray structures of membrane proteins.
MPID is a PSI:Biology center investigating the structures of viral, bacterial and human membrane proteins involved in pathogenesis. Under the leadership of the principal investigator, Petra Fromme, the MPID Center is trying to use the biological theme of membrane proteins in infectious diseases as the basis for the determination of novel membrane protein structures and to develop new technologies for high throughput membrane protein expression, isolation, functional characterization, crystallization and structure determination.
Membrane proteins represent > 60 percent of all drug targets and are also key players in the pathogenesis of infectious diseases. A critical step for the elucidation of the complex processes that are catalyzed by membrane proteins is an understanding of the structure, dynamics and function of membrane proteins. Our knowledge of processes catalyzed by membrane proteins suffers mainly from the lack of information concerning their structure as less than 300 different membrane protein structures are known at present. The MPID Center targets membrane proteins of important viral and bacterial pathogens, their infectious pathways, and molecules involved in host defense against the pathogens. The structural determination of each of the targets may provide important clues for the understanding of the infectious disease pathways and can therefore form the basis for the treatment and prevention of infectious diseases.
BioXFEL is a Science and Technology center using X-ray lasers to image biomolecular machines in motion. X-ray lasers provide snapshots of unprecedented clarity depicting the building blocks of life. The motions and arrangements of these blocks underlie all biological function. The mission of BioXFEL is:
To use X-ray lasers, to watch biomolecular machines in operation, the better to understand how life works at the molecular level.
To understand how these molecular machines support life on Earth.
To invent, discover, develop and provide new tools and training to bring X-ray laser technology to the wider scientific community
Center for Bio-Inspired Solar Fuel Production (BISfuel) (DOE)
BISfuel is an Energy Frontier Research Center with the mission to construct a complete system for solar-powered production of fuels such as hydrogen via water splitting. Design principles are drawn from the fundamental concepts that underlie photosynthetic energy conversion.
A major challenge facing humanity is developing a renewable source of energy to replace our reliance on fossil fuels. The ideal source will be abundant, inexpensive, environmentally clean, and widely distributed geographically. Energy from the sun meets these criteria. Unfortunately, practical, cost effective technologies for conversion of sunlight directly into useful fuels do not exist, and new basic science is required. A blueprint for storage of solar energy in fuels does exist, however, in photosynthesis. Indeed, all of the fossil-fuel-based energy we consume today derives from sunlight that was harvested by photosynthetic organisms.
Recognizing the need for new science, the DOE established the ASU Center for Bio-Inspired Solar Fuel Production in 2009. The Center involves 11 faculty from the Department of Chemistry and Biochemistry and is housed within the ASU Center for Bioenergy and Photosynthesis. The Solar Fuel Center consists of faculty, research associates, graduate students and undergraduate researchers dedicated to solving the renewable energy problem.