Director:
Center Association: Center for
Biophysical Sciences and Engineering (CBSE),
Established: 1975
The X-Ray Crystallography Shared Facility
provides CCC members, UAB investigators, and regional scientists access to a
premiere facility for protein crystal structure determinations for both aqueous
and membrane proteins. The facility
includes automated high throughput systems for crystallization screening
capable of preparing up to 10,000 crystallization experiments a day in
nanoliter to microliter volumes as well as other novel techniques to optimize
crystal growth in order to obtain the diffraction quality crystals necessary
for structure determination. The CBSE
facility maintains four operational bays for in-house diffraction data
collection along with access to two dedicated synchrotron beamlines at the
Argonne National Laboratory. Our
facility positions researchers with competitive advantages to rapidly determine
protein structures of interest.
Facility Description
The facility is located in The Center for
Biophysical Sciences and Engineering building and operated under the direction
of Dr.
1) High Throughput (HTP) protein crystallization
and Co-Crystallization screening facility.
This 680 square foot facility utilizes the following integrated platform
of systems:
·
A HTP automated system for rapid generation and optimization of
specialized solutions used in crystallization screens (Recipe Maker™).
·
A new (2008) Rigaku Phoenix RE Liquid Handling System for high
throughput low volume protein crystallization experimentation.
·
Two automated HTP liquid dispensing systems for submicroliter volumes
(the custom built NanoScreen™ and the commercial Cartesian HoneyBee™ System).
·
An automated microchip system for free interface diffusion
crystallization along with an automated imaging station for microchips (a.k.a.
the Fluidigm Topaz Microchip System™).
·
An automated HTP capillary counter diffusion system (the HoneyComb by
Genomic Solutions™).
·
A HTP automated system for optical recognition and scoring of crystals
(Crystal Score™).
·
A dynamically controlled crystal growth kinetic system for optimization
of crystal growth (Vapor Pro™).
·
Use of a virtual screening program (utilizing predictive algorithms) for
the optimization of crystallization conditions, thus reducing amount of sample
and number of experiments needed to define high quality crystal growth. This technology supports efforts to find new
or optimize present conditions that improve crystal growth for both soluble and
membrane proteins.
·
HTP Self Interaction Chromatography, a customized HPLC system for
accurate protein-protein interaction experiments for the determination of second
virial coefficient measurements of proteins. Improved crystallization parameters for proteins
as well as optimizing solutions for the stabilization of protein pharmaceutical
formulations represents examples of protein solution phenomena that can be
measured with thermodynamics measurements of protein-protein interactions. We can measure PPI through the determination
of the second virial coefficient. The
CBSE has developed a - HTP analytical method and automated system that allows
users to quickly determine optimal solutions.
2) Synchrotron X-ray source. Since 1997, UAB has been a member of the
Southeast Regional Collaborative Access Team (SERCAT) with dedicated access to
two of the most powerful beamlines at the Argonne National Laboratory in
3) Laboratory X-ray source. This 2,116 square foot facility maintains
four fully operational bays for in-house X-ray diffraction experiments. The CBSE has 12 PhD level crystallographers
in house.
4) Crystallography Computing. This 646 square foot computing facility
provides a central computing network system for data processing, data transfer,
structure determination, graphics, and database management in conjunction with
all the latest software modeling programs available. Remote access to a UAB
128-Beowulf Intel® processor-based Linux cluster allows “pipeline”
approaches to be used to automate and accelerate the structure determination
process.
Users of this facility can also contact the CBSE
for information on our Biomolecular Physics laboratory and the availability of
these complimentary techniques used by researchers to support crystallization
and compound development. The CBSE
Biomolecular Analysis Group currently uses biocalorimetry data and other
biophysical tools to enhance the design and optimization of lead
compounds. Isothermal Titration Calorimetry and Differential
Scanning Calorimetry can advance your research with applications in: 1) protein
engineering, detecting misfolded domains; 2) proteomics, energetic domain architecture;
3) optimization of crystallization conditions, 4) biopharmaceutical formulations;
5) drug discovery: developing universal assay for lead identification,
development; and 6) understanding the importance of functional groups,
salvation, hydrophobicity and conformation.
Research Information
The facility provides structural biology
support from cloning and expression through structure determination and
combinatorial chemistry for researchers interested in macromolecular
structure-function relationships and drug discovery via intelligent or
structure-based combinatorial design. Protein structural
information is used for the discovery and synthesis of complimentary compounds
that augment or inhibit the protein's biological activity for drug discovery
applications. Current drug development programs supported
by the facility focus on cancer, infectious diseases, cardiovascular disease,
bacterial infections, and immune response.
The CBSE has a particular interest in crystallizing and solving membrane
protein structures.
Contact Information
Core Director:
Email:
Delucas@cbse.uab.edu
Phone:
205-934-5329
Web site: http://www.cbse.uab.edu/
Approved by:
Date: March 18, 2008
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