UCSF Drug Development Capabilities & Resources (10/19/04)

Research Facilities

1. CAT - Center for Advanced Technology
   Contact: Douglas Crawford, Douglas.Crawford@ucsf.edu

   The Center for Advanced Technology is a collection of equipment that enables laboratories at UCSF (and our collaborators from other institutions) to carry out high-throughput experiments. The focus and the major benefits of facility are to:
   
   

   • Enable the rapid completion of genomic and proteomic projects
   • Centralize the information related to these projects
   • Ensure that the information we provide is the most up-to-date
   • Provide training for performing genomic and proteomic experiments
   • Provide training on the related equipment
   • Provide training in the bioinformatics required for interpretation of genomic and proteomic experiments
   • Manage the use and sharing of the related equipment

   Equipment list:

   • Automated microarrayer is a linear servo motor-powered microarrayer, constructed according to the M-Guide. It will accommodate 261 1" glass slides and can be used with up to 48 printing tips.
   • Biomek FX - 96-channel pipetting robot with extensive plate handling capabilities.
   • Multimek performs 96-channel pipetting tasks, like the Biomek FX, but it has a smaller plate capacity.
   • CAPS colony arrayer is a three-axis gantry robot with a floating-pin head designed for mating and replicating yeast colonies. It will accommodate 20 rectangular agar plates or microtiter plates and uses a 384-tip replicator head.
   • HiGro incubator shaker can accommodate 24 deep-well 96-well plates. Each pod holds 6 plates and has independent temperature control, so it will accommodate multiple simultaneous runs.
   • Tetrad PCR machines - each will accommodate 4 96-well PCR plates.
   • Oligo Synthesizer performs the parallel synthesis of 96 oligonucleotides up to 60 bases in length

2. BASC - Bay Area Screening Center
   Contact: Gregg Kyle, gkyle@research.ucsf.edu

   The primary mission of BASC is to enable biological research by providing access to the knowledge, equipment, and reagents needed to carry out high throughput screening in biochemical and cellular assay systems. BASC seeks to provide an environment in which one can carry out appropriate projects that utilize high throughput screening techniques without heavy investment in infrastructure or purchase of extensive libraries.
   
   

   • Design of Libraries. BASC provides access to a number of computational tools for focusing libraries for screens.
   • Chemical Libraries. BASC currently holds a library of approximately 78,000 highly diverse small molecules suitable for cellular and biochemical screens against a variety of targets
   • Screening Methodologies. BASC is capable of carrying out assays in a variety of formats. Both biochemical and cellular assays can be fully automated for purposes of a screen

3. CCD - Center for Chemical Diversity
   Contact: Gregg Kyle, gkyle@research.ucsf.edu

   The CCD is UCSF's campus-wide facility for the design and synthesis of focused parallel libraries.

   Current Procedures

   • Spatial Arrays / Parallel Libraries
   • Manual Addition of Reagents
   • Compound purification
   • Structure verification
   • Library Sizes of 50 - 1000's

4. LSD - Large Scale Docking - Virtual Screens
   Contact: Gregg Kyle, gkyle@research.ucsf.edu

   Large Scale Docking is a software pipeline for automated protein structure modeling and ligand docking. This pipeline will integrate modules for (i) automated comparative protein structure modeling; (ii) identification and annotation of protein functional sites based primarily on homology considerations; (iii) refinement of comparative protein structure models by molecular mechanics methods; (iv) building of virtual libraries of ligands; (v) docking of the ligand libraries against the refined protein structure models; (vi) assessment of the accuracy of the complex models and predicted ligands; and (vii) storing the computational results in a database with a web-based graphical interface for flexible access to the data. This pipeline will be optimized for a cluster of processors, and will allow automated docking calculations for thousands of proteins and hundreds of thousands of ligands.

5. GMP Cell Facility - UCSF Diabetes Center
   Contact: Greg Szot, 415.514.2108 (Bluestone Lab)

   The UCSF Diabetes Center hosts a facility where donor pancreases are processed to harvest islet cells for transplantation into diabetic patients. The GMP facility was designed with a unidirectional workflow, including a preparation area, sterile room (class 100), three independent suites, and a decontamination room. Of the three suites, two currently have space available: a 200 sq. ft. self-contained negative pressure space that is suitable for viral vector studies; a 300 sq. ft. space that is partially available. Facility managers are available to ensure that users can write and follow proper cGMP protocols.

6. Drug Product Services Laboratory - UCSF Clinical Pharmacy
   Drug Product Services Laboratory: http://www.ucsf.edu/dpsl/
   Contact: Joanne Whitney, Director, whitney@itsa.ucsf.edu, 415.476.1444

   The Drug Product Services Laboratory provides investigators with drug dosage forms not available commercially. For many years, it was registered with the FDA but now operates as a licensed compounding pharmacy owned by the Department of Clinical Pharmacy. Good Manufacturing Procedures are still used for the compounding of products. The laboratory makes parenteral preparations and ointments, gels, suppositories, suspensions, oral solutions and capsules for patient use and for research studies.

   The Drug Product Services Laboratory is expert in preparing active and placebo capsules for clinical drug studies. Tablets can be reduced to powders where powdered USP grade drugs are unavailable, transferred to capsules and weight matched with placebo capsules. Sustained released tablets can be encapsulated whole and weight matched with tablet placebos. Sustained release capsules can be made.

   Drug Product Services offers consultation on the management of medications and placebo forms needed for clinical drug studies. The laboratory supplies investigators with information of how much medication is needed and in what form. The laboratory calculates and formulates the procedures ensuring the production of optimum number and structure of dosage forms for the study. The laboratory also determines how these dosage forms can best be prepared and packaged to ensure success of the project. The laboratory is expert at choosing and preparing the best placebo preparation for the study and handles all the logistics involved in their preparation and packaging. Drug Product Services also insures that investigators obtain drugs and chemicals used in the compounding of dosage forms at the lowest prices. Blinding of active and placebo preparations of all dosage forms and maintenance of the blinded information is performed.

   Large or small quantities of drug dosage forms may be compounded. All packaging, sealing and labeling is performed to produce a quality product of pharmaceutical elegance.

7. Mouse Strain Rederivation Program
   Laboratory Animal Resource Center
   See: http://www.larc.ucsf.edu/services/serviceIndex.asp

   UCSF has established a new core facility to rederive mouse strains by embryo transfer, considered the most secure means for moving mouse strains from conventional facilities to specific pathogen-free facilities.