Acquisition of an automated crystal imager

ABSTRACT Funds are requested to acquire a JanSci UVEX-PS600 imaging system to visualize, interpret, evaluate and record crystallization experiments generated during high throughput screening to identify crystallization conditions for our biological macromolecules. UTMB has seven dedicated protein crystallography groups, as

well as a User Facility that serves researchers using protein crystallography as a secondary technique. Our researchers leverage structural biology to investigate targets involved in neuropsychiatric disorders, infectious diseases, immune defense, cancer, and diabetes-related disorders, as well as basic biological

mechanisms. The targets span a wide range of proteins, protein:protein complexes, protein:DNA complexes, protein:drug complexes, and viruses. Many of our targets are very challenging: for example, large multi-domain macromolecules, ternary protein complexes, glycosylated proteins and specific protein:drug complexes so that

we often need to screen thousands of crystallization conditions before promising hits are found which can be leveraged to grow crystals suitable for high resolution diffraction experiments. To enable structure determination, as well as speed up and decrease the cost of crystallizing our targets, we need an imaging

system that can efficiently identify successful crystallization conditions. The system must 1) drive the science forward by identifying crystalline vs amorphous protein precipitate, and protein vs salt crystals; 2) image and evaluate thousands of different crystallization experiments with high resolution and high speed; and 3)

handle a very large amount of crystallization data from many different projects in a multi-user environment. Currently, the structural biology groups at UTMB are generating ~1300+ crystallization plates per year (and rising) supported by $15M in NIH funding (9 R01s). We have no access to a working crystallization

plate imager at UTMB. Acquiring a UVEX-PS600 system and CrystalDetect/WebView software from Jan Scientific will enable us to image crystallization experiments efficiently and at high resolution using both visible and UV wavelengths to identity promising crystals, and provide enough imaging capacity to work with 628

crystallization plates at a time without manual intervention. The new instrument will be housed in the recently renovated Sealy Center for Structural Biology and Molecular Biophysics (SCSB) at UTMB, and will be supported by the SCSB. A Ph.D.-level X-ray Facility Manager, fully supported by the SCSB, will oversee the system. A

steering committee composed of a mix of users, as well as arm’s length experts, will provide oversight of the policies relating to access, training, and maintenance, and it will be overseen by an established advisory committee. The UVEX-PS600 system will serve our investigators carrying out NIH-funded projects at UTMB that

involve structural biology; access will also be provided to users at the SCSB and new faculty to facilitate their competition for NIH support. In addition, members of the Gulf Coast Consortium will have access to this equipment through the SCSB to perform pilot experiments on a wide range of structural biology projects.