High-throughput Crystallization Imaging System

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Three dimensional structures of health-related proteins and their complexes are indispensable to identify proper protein function. The gold standard for three-dimensional protein structure determination is X-ray crystallography. With advances in data collection and structure determination, protein crystallization represents the major bottleneck that impedes the entire structure determination process and significantly inhibits research progress.******This application requests funding for a state-of-the-art, high-capacity crystallization “hotel” and imaging suite (“RockImager”). The proposed equipment will allow researchers to grow protein crystals in a tightly controlled environment, automatically screen and image thousands of crystallization conditions using visible/UV light optics and analyze results from their office or home computers. The system is urgently needed to replace antiquated protein crystallization facilities at Western, accelerate the crystal discovery process and create a high throughput, open-access environment that will give our research groups an internationally competitive edge.******The proposed equipment will support NSERC-funded researchers from more that 20 research groups at Western and surrounding institutes in the London region. It will expedite crystallization of proteins involved in calcium-signalling, protein degradation, energy coupling and plant development. The ensuing X-ray structures will provide atomic level details of proteins and complexes involved in Parkinson's disease, cancer, antibiotic development and disease-causing fungal toxins. Examination of these three-dimensional shapes are the foundation for understanding how these systems function in healthy and diseased states.******The proposed equipment will benefit multiple research programs by providing a modern, systematic approach that will alleviate the crystallization bottleneck and lead to increased X-ray structure productivity. The automated imaging system will provide PIs and HQP with huge time-savings allowing more efficient use of research time. Newly determined three-dimensional structures of proteins and complexes have the potential to be used as templates to design molecules that limit disease progression or combat agricultural pests and toxins, both heavy burdens on the Canadian economy. The equipment will also be central to training and recruitment of HQP where the RockImager will expose students to modern methods of crystallization required in the most competitive research environments. It will provide analytical and computational skills for HQP needed in academia, government agencies and biotechnology/chemical industries.******Overall the acquisition of this equipment, along with a recent Western-financed upgrade to our data collection instrument, is essential to gain fundamental insights into protein function with the potential for significant returns to the greater scientific community. *** **