Enablling protein structure with Protein Crystallogaphy in support of Drug Discovery.

• Managed two Research Associates and collaboratively produced an outstanding output of 8000 protein crystals, 1600 X-ray datasets, and 820 protein structures occupied with small molecule inhibitors from 2005 to 2010.• Enabled first elucidation of five new protein structures. • Developed large scale protein purification protocols using exploratory multi-variable analytical chromatography runs on BioCad instrument (from Perseptive Biosystems). • Validated acoustic liquid dispensing technology for application in the handling of nano liter volumes of protein thereby enabling a 10 fold reduction in protein consumption.• Wrote practical methods to acoustically dispense nanoliter aliquots of protein to thousands of experiments in crystal screen matrices.• Pioneered the integration of four stand alone instruments to deliver reliable completion of 48 crystallization experiments per minute. The integration included liquid dispenser (Cybio-ag.com), plate transfer (peakrobotics.com), plate sealer (abgene.com) and portable stackers for export into downstream imager.• Faciliated development of data export engine for the Matrix Maker liquid dispenser to export xml files destined for foreign databases such as that on the Crystal Farm imager. • Wrote and optimized custom liquid-dispensing programs for instruments Crystal Creator and CybiWell (Cybio-ag.com), Hummingbird (GenomicSolutions.com) and ATS100 acoustic dispenser (EDCbiosystems.com). • Initiated and managed collaboration with Corning, which resulted in the generation of one of today's best crystallography plates, Corning # 3785.• Designed the creation of a novel commercial crystal screen that features systematic presence of up to two precipitants in crystal screens (axygen.com). • Collaboratively impacted development of over a dozen protein production protocols by plotting alternate purification schemes as well as proposing specific mutants in support of protein crystallography an HTS.

• Thoroughly examined numerous variables affecting soluble expression of p38 mitogen-activated Protein Kinase (p38α) including sampling of ten E. coli strains, post induction temperature, growth medium and harvesting times. The end result was 40 mg of soluble protein per liter of culture.• Developed chromatography protocol to separate three phospho-species of p38α by hydrophobic interaction on Fast Protein Liquid Chromatography (FPLC) instrument.• Experimentally established robust and efficient 3-column FPLC protocols for the purification of catalytically active 15-Lipoxigenase (15-LO), p38α, and human macrophase elastase (HME).• Enabled HTS screening campaigns with stable supply of active 15-LO, p38α and HME.• Established purification of Cathepsin K in the presence of inhibitors by size exclusion.• Analyzed protein samples by Light Scattering for informed selection of buffer additives, and Mass Spec for characterization.