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Buffalo Center of Excellence in Bioinformatics Russ Miller Director, Center for Computational Research UB Distinguished Professor, Computer Science & Engineering Senior Research Scientist, Hauptman-Woodward Medical Inst

WNY Biomedical Advances PSA Test (screen for Prostate Cancer) Avonex: Interferon Treatment for Multiple Sclerosis Artificial Blood Nicorette Gum Fetal Viability Test Implantable Pacemaker Edible Vaccine for Hepatitis C Timed-Release Insulin Therapy Anti-Arrythmia Therapy Tarantula venom Direct Methods Structure Determination Listed on “Top Ten Algorithms of the 20th Century” Vancomycin Gramacidin A High Throughput  Crystallization Method: Patented NIH National Genomics Center: Northeast Consortium Howard Hughes Medical Institute: Center for Genomics & Proteomics

Animal Models and Preclinical Toxicology

Bioinformatics in Buffalo UB Center for Advanced Bioengineering & Biomedical Technologies $1M/yr NYS Med Tech for Product Dev & Commer. Center Disease Modeling & Therapy Discovery UB, HWI, RPCI, Kaleida $15.3M NYS Software, device development, and drug therapies Buffalo Center of Excellence in Bioinformatics UB, HWI, RPCI $61M NYS $3M Federal Government $151 Corporate Funding

Buffalo Center of Excellence in Bioinformatics Act as a research, development, education, and economic resource for industries based on bioinformatics, including information technology, biotech, and pharmaceuticals. Combine state-of-the-art computational facilities with high-throughput experimental facilities to enable the development of new medical treatments. Develop and exploit new algorithms for data acquisition, storage, management, and transmission.

BCOEB Partners Core Partners University at Buffalo Hauptman-Woodward Medical Research Institute Roswell Park Cancer Institute Corporate Partners Amersham Pharmacia, AT&T, Beckman Coulter, BioPharma Ireland, Bristol Myers Squibb, Confederation of Indian Industries, Dell, General Electric, Human Genome Sciences, HP, Immco, InforMax, Invitrogen, Pfizer Pharmaceutical,      Q-Chem, Sloan Foundation, SGI, Stryker,        Sun, 3M, Veridian, Wyeth Lederle, Zeptometrix WNY Business Community

Life Sciences Complex (Buffalo-Niagara Medical Campus) UB $52M CoE in Bioinformatics Research and business partners 225 employees and business associates 150,000 sq ft: 50% labs, 50% computational facilities

Experimental Facilities I Molecular Targeting Laboratory Screen 30-50K compounds every 3 months Apply compound to cell (different genes treated w fluor markers) Rapidly identify effect on specific gene expression pathways Gene Expression Laboratory High-throughput microarray and gene chip Discover new genes, their functions, and pathways Proteomics and Molecular Kinetics Lab Identify molecular targets found in Gene Expression Lab Disease Modeling Laboratory In vivo testing (flies, mice, baboons,…) Gene targeting and genetic mapping facilities

Experimental Facilities II Bioengineering Support Laboratory Capabilities in photonics and nano-tech research E.g., handheld devices to test for diseases Protein Scale-Up and Purification High-Throughput Robotic Combinatorial Chemistry/Parallel Synthetic Chemistry Capabilities Drugs created robotically; Tested for interaction with target protein Rapid identification of a large number of potential drugs Public Health and Molecular Pathology Tissue repositories; disease gene maps; medical informatics High-Throughput Search Process for Structural Biology Tests 1536 “chemical cocktails” to determine effective parameters for crystallization

Center for Computational Research High-Performance Computing and High-End Visualization 70 Research Groups in 27 Depts 25 Companies and Institutions Ext Fund: $108M; Vendor: $41M Sample Areas Computational Chemistry Ground Water Modeling Geophysical Mass Flows Urban Visualization and Simulation Medical Imaging Networked Multimedia Training Workshops; Courses Degree Programs

Computational Resources Dell Linux Cluster - #22 in world! 600 P4 Processors  (2.4 GHz) 600 GB RAM; 40 TB Disk Dell Linux Cluster - #187 in world 4036 Processors (PIII 1.2 GHz) 2TB RAM; 160TB Disk; 16TB RD

Visualization Resources Fakespace ImmersaDesk R2 Portable 3D Device VREX VR-4200 Stereo Imaging Projector Portable projector works with PC Tiled-Display Wall 20 NEC projectors; Dell PCs; Myrinet; 15.7M pixels Access Grid Node Group-to-Group Communication Commodity components SGI Reality Center 3300W Dual Barco’s on 8’´4’ screen

Antibiotics & Supercomputers Vancomycin solved with SnB (UB/HWI) SnB: “Top Algorithms of the Century” “Antibiotic of Last Resort” Original molecular structure required 5 months (Re)solved in a single day on CCR’s supercomputers Current Efforts: Grid, Collaboratory, Intelligent Learning

Protein Folding Ability of proteins to perform biological function is attributed to their 3-D structure. Protein folding problem refers to the challenge of predicting 3-D structure from amino-acid sequence. Solving the protein folding problem will impact drug design.

Protein Dynamics Dynamics of Hemoglobin (Example) 50 Days of Processing on 16 Processors (800 CPU Days) Key White – Heme Groups Red – Phe97 Red – Oxygen (in the subunit at bottom) Green – His 69 and 101 Blue – Tyr 72 Cyan (Ball) – Water Molecules Yellow – Helix E/F Interest Flip of the Phe97 ring at top Water movement around Phe97 Heme-heme relative movement

3D Medical Visualization App Collaboration with Children’s Hospital Leading miniature access surgery center Application reads data output from a CT Scan Visualize multiple surfaces and volumes Export images, movies or CAD representation of model

Multiple Sclerosis Project Collaboration with Buffalo Neuroimaging Analysis Center (BNAC) Developers of Avonex, drug of choice for treatment of MS MS Project examines patients and compares scans to healthy volunteers

Multiple Sclerosis Project Compare caudate nuclei between MS patients and healthy controls Looking for size as well as structure changes Localized deformities Spacing between halves Able to see correlation between disease progression and physical structure changes

Academic Programs Master’s Program in Bioinformatics (Sloan) Advanced Degrees under development Pharmacometrics, Biophotonics, Computational Chemistry, Molecular Biology School of Informatics (AT&T curr. dev.) UB-HWI Dept. of Structural Biology Complementary Degrees Canisius College and Niagara University

Contact Information miller@buffalo.edu www.ccr.buffalo.edu www.bioinformatics.buffalo.edu