Buffalo Center of Excellence in Bioinformatics

Russ Miller, Director

Center for Computational Research

Recent Biomedical Advances
(Buffalo, NY)

Edible Vaccine for Hepatitis C

PSA Test

Avonex: Interferon Treatment for Multiple Sclerosis

NIH National Genomics Center: Northeast Consortium

Howard Hughes Medical Institute: Center for Genomics & Proteomics

Artificial Blood

Fetal Viability Test

Anti-Arrythmia Therapy – tarantula venom

Direct Methods Structure Determination (Dr. Herbert Hauptman)

Listed on poster “Top Ten Algorithms of the 20^th Century”

Vancomycin

Gramacidin A

High Throughput Crystallization Method: patented

Timed release Insulin therapy

Bioinformatics

The use of HPC to analyze data generated by the Human Genome Project to improve medical treatment.

Precise sequence of ~30K human genes have been mapped

Critical to elucidate the function of each gene.

Leads to greater understanding of human development.

Potential to treat many diseases, including AIDS cancer, MS, and Alzheimer’s and provide personalized treatment.

From Human Genome

Locate genes (tens of thousands in human body)

Determine what protein a gene regulates (millions of proteins in body)

Determine structure

Determine protein function

Devise drugs to block or enhance protein function

Bioinformatics in Buffalo

WNY STAR Center for Advanced Medical Technologies

$1M NYS; UB & RPCI

Medical Technologies for Product Development and Commercialization

NYSTAR in Disease Modeling and Therapy Discovery

$15.3M NYS; UB, HWI, RPCI, Kaleida

Software, device development, and drug therapies

Buffalo Center of Excellence in Bioinformatics

$75M NYS, $3M US; UB, HWI, RPCI, Industry

www.bioinformatics.buffalo.edu

Goal: Develop New Treatments for Disease

Buffalo Center of Excellence
in Bioinformatics (BCOEB)

Act as a research, development, education, and economic resource for industries based on bioinformatics, including information technology, biotechnology, and pharmaceuticals.

Generate medically and biologically important information

Genomics: Identify Gene

Molecular Biology: Express protein (gene product)

Structural Biology: Determine shapes of protein

Indicates use of protein in body

Suggests drug designs to assist or inhibit protein action

Drugs interact strongly with proteins in structure-specific ways

BCOEB Facilities
(Computational)

Center for Computational Research

Top 10 Academic Supercomputing Center

High-Performance Computing & High-End Viz

High-Speed Communication

I2, vBNS, Abilene, NYSERNET

WNY Regional Fiber Network Initiative

UB, City of Buffalo, Erie County

BCOEB Facilities
(Analysis of Genetic Material and Functional Determination)

Molecular Targeting Laboratory

Screen 30-50K compounds every 3 mos

Determine effects on specific gene expression pathways

Gene Expression Laboratory

Dissection of target gene product & gene expression pathway

Proteomics and Molecular Kinetics Lab

Identify molecular targets found in Gene Ex. Lab

Disease Modeling Laboratory

Gene targeting and genetic mapping facilities

Bioengineering Support Laboratory

Capabilities in photonics and BioMEMs

Additional BCOEB Facilities

High-Throughput DNA Micro-Array

Full spectrum analysis of genomes and expression

Protein Scale-Up and Purification

High-Throughput Robotic Combinatorial Chemistry/Synthetic Chemistry Capabilities

High-Throughput Search Process for Structural Biology

Tests 1536 “chemical cocktails” to determine effective parameters for crystallization

BCOEB Partners

Matching Funds ($151M)

Amersham Pharmacia, AT&T, WNY Business Community, Compaq, Dell, InforMax, Sloan Foundation, SGI, Stryker, Sun, Q-Chem, Veridian

Research

Amersham, Bristol-Myers Squibb, Compaq, Human Genome Sciences, Immco, InforMax, Invitrogen, Pfizer Pharmaceutical, Wyeth Lederle, Zeptometrix

Support
(2001-2002)

New York State ($50M + $25M)

Federal ($3.1M + ?)

Proteomics ($1.5M)

Disease Pathogens and Physiology ($27M)

Drug Discovery ($6M)

Genomic and Proteomic Infra. ($1.8M)

Genomics ($4.7M)

Information Technology ($12.3M)

A New Economy

STOR: Office of Science, Tech Transfer, and Economic Outreach

Support product and business development

BuffLink: Private sector will promote commercialization of cutting-edge research

Venture Capital

Compaq ($10M)

Buffalo Business Community ($15M)

Corporate Partnerships

WNY Regional Fiber Network Initiative

Life Sciences Complex
(Buffalo-Niagara Medical Campus)

Buffalo Center of Excellence in Bioinformatics

$42M Building for research and business partners

200 employees and business associates

150,000 sq ft: 50% research labs, 25% computational facilities; 25% workforce training

Roswell Park Cancer Institute Research Bldg

$60M Building to replace outmoded facilities

60 PIs and 200 support staff

170,000 sq ft: 85% research labs and 15% support

Academic Programs in
Bioinformatics

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

Molecular Structure Determination

SnB Software by UB/HWI

“Top Algorithms of the Century”

Critical to Rational Drug Design

Important Link in Structural Biology

Antibiotics & Supercomputers

Vancomycin solved with SnB

“Antibiotic of Last Resort”

Original molecular structure required 5 months of computing to solve

(Re)solved in a single day on CCR’s supercomputers

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

Children’s Hospital CT

3D Reconstruction of CT Dataset

Created with the Visualization Toolkit (VTK) on a Linux Workstation

3D Isosurface Clearly Shows Structure that is Nearly Impossible to Determine from 2D Slices

Confocal Microscopy

3D Reconstruction of an Oral Epithelial Cell

Translucent White Surface Represents the Cell Membrane

Reddish Surface Represents Groups of Bacteria

CCR
Overview

Leading U.S. Academic Supercomputing Center

High-Performance Computing

High-End Visualization

Support ~80 Groups in ~25 Depts

Education/Outreach/Training

H.S. Summer Program

Work with Local Industry & Local Colleges

Hosts Meetings/Provides Tours

M.S. Certificate Program in Computational Science

Sample CCR-Supported Research (1)

Structural Biology

Molecular Structure Determination & DNA Sequence Analysis

Protein Folding

Computer simulations determine the 3D structure of proteins.

Environmentally Friendly Solvents

Study supercritical CO₂ as a solvent to reduce the need for toxic solvents.

Groundwater Modeling

Predict contaminant flow in groundwater & migration into streams and lakes.

Industrial Design Optimization

Design, modify, and perfect new products at reduced cost.

Fluid Dynamics

Modeling turbulent flows and combustion in order to improve design of chemical reactors, turbine engines, and airplanes.

Volcanology

Study of volcanoes for risk assessment. Modeling of lava flows and mudslides.

Sample CCR-Supported Research (2)

Financial Analysis

Datamining analaysis for prediction.

Dental Implant Design

Simulation and modeling of a dental implant in a jawbone to reduce failure rate.

Physiology

Flow & regulation in kidney. Flow altered by aneurysm.

Biophysics

Measure protein conformational dynamics.

Visualization & Multimedia

Peace Bridge, Buffalo Medical Corridor, CCR, Events. Networked media. Art.

Semiconductor Manufacturing

New processes & chemicals to improve the manufacturing of computer chips.

Classics

Digital reconstruction of Assyrian Palace.

CCR Computing (0.4TFlops)

SGI Origin2000

128 Processors (250 MHz)

32 GB RAM

400 GB Fibre Channel Disk Storage

IBM RS/6000 SP

78 Processors

26 GB Ram, 640 GB Disk Storage

Sun Microsystems Cluster

48 Sun Ultra 5 Workstations (333MHz)

32 Sunblades (750MHz)

Myrinet + 100BT Ethernet

SGI Intel Linux Cluster

150 Pentium III Processors (1 GHz)

75 GB RAM, 2.5 TB Disk Storage

Myrinet2000 + 100BT Ethernet

CCR Visualization

Manufacturing

Medical Imaging

Computational Science

Simulation & Modeling

Historical Reenactments

Multimedia Presentations

Future Acquisitions

Hardware

Cluster Computing: 2-6TFlops

ACCESS Grid

Commodity Viz Clusters

Portable Viz Systems

Additional Viz Workbench

Commodity Projection Systems

Software

Bioinformatics

Modeling and Simulation Packages

Database & Data Mining

Storage Management

"CCR Grand Opening"

CCR Grand Opening

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


	Edible Vaccine for Hepatitis C
	PSA Test
	Avonex: Interferon Treatment for Multiple Sclerosis
	NIH National Genomics Center: Northeast Consortium
	Howard Hughes Medical Institute: Center for Genomics & Proteomics
	Artificial Blood
	Fetal Viability Test
	Anti-Arrythmia Therapy – tarantula venom
	Direct Methods Structure Determination (Dr. Herbert Hauptman)
		Listed on poster “Top Ten Algorithms of the 20^th Century”
	Vancomycin
	Gramacidin A
	High Throughput Crystallization Method: patented
	Timed release Insulin therapy


	The use of HPC to analyze data generated by the Human Genome Project to improve medical treatment.
	Precise sequence of ~30K human genes have been mapped
		Critical to elucidate the function of each gene.
		Leads to greater understanding of human development.
		Potential to treat many diseases, including AIDS cancer, MS, and Alzheimer’s and provide personalized treatment.
	From Human Genome
		Locate genes (tens of thousands in human body)
		Determine what protein a gene regulates (millions of proteins in body)
		Determine structure
		Determine protein function
		Devise drugs to block or enhance protein function


	WNY STAR Center for Advanced Medical Technologies
		$1M NYS; UB & RPCI
		Medical Technologies for Product Development and Commercialization
	NYSTAR in Disease Modeling and Therapy Discovery
		$15.3M NYS; UB, HWI, RPCI, Kaleida
		Software, device development, and drug therapies
	Buffalo Center of Excellence in Bioinformatics
		$75M NYS, $3M US; UB, HWI, RPCI, Industry
		www.bioinformatics.buffalo.edu
	Goal: Develop New Treatments for Disease


Act as a research, development, education, and economic resource for industries based on bioinformatics, including information technology, biotechnology, and pharmaceuticals.
Generate medically and biologically important information
	Genomics: Identify Gene
	Molecular Biology: Express protein (gene product)
	Structural Biology: Determine shapes of protein
		Indicates use of protein in body
		Suggests drug designs to assist or inhibit protein action
Drugs interact strongly with proteins in structure-specific ways


Center for Computational Research
	Top 10 Academic Supercomputing Center
	High-Performance Computing & High-End Viz
High-Speed Communication
	I2, vBNS, Abilene, NYSERNET
	WNY Regional Fiber Network Initiative
		UB, City of Buffalo, Erie County


	Molecular Targeting Laboratory
		Screen 30-50K compounds every 3 mos
		Determine effects on specific gene expression pathways
	Gene Expression Laboratory
		Dissection of target gene product & gene expression pathway
	Proteomics and Molecular Kinetics Lab
		Identify molecular targets found in Gene Ex. Lab
	Disease Modeling Laboratory
		Gene targeting and genetic mapping facilities
	Bioengineering Support Laboratory
		Capabilities in photonics and BioMEMs


	High-Throughput DNA Micro-Array
		Full spectrum analysis of genomes and expression
	Protein Scale-Up and Purification
	High-Throughput Robotic Combinatorial Chemistry/Synthetic Chemistry Capabilities
	High-Throughput Search Process for Structural Biology
		Tests 1536 “chemical cocktails” to determine effective parameters for crystallization


	Matching Funds ($151M)
		Amersham Pharmacia, AT&T, WNY Business Community, Compaq, Dell, InforMax, Sloan Foundation, SGI, Stryker, Sun, Q-Chem, Veridian
	Research
		Amersham, Bristol-Myers Squibb, Compaq, Human Genome Sciences, Immco, InforMax, Invitrogen, Pfizer Pharmaceutical, Wyeth Lederle, Zeptometrix


	New York State ($50M + $25M)
	Federal ($3.1M + ?)
	Proteomics ($1.5M)
	Disease Pathogens and Physiology ($27M)
	Drug Discovery ($6M)
	Genomic and Proteomic Infra. ($1.8M)
	Genomics ($4.7M)
	Information Technology ($12.3M)


	STOR: Office of Science, Tech Transfer, and Economic Outreach
		Support product and business development
	BuffLink: Private sector will promote commercialization of cutting-edge research
	Venture Capital
		Compaq ($10M)
		Buffalo Business Community ($15M)
	Corporate Partnerships
	WNY Regional Fiber Network Initiative


	Buffalo Center of Excellence in Bioinformatics
		$42M Building for research and business partners
		200 employees and business associates
		150,000 sq ft: 50% research labs, 25% computational facilities; 25% workforce training
	Roswell Park Cancer Institute Research Bldg
		$60M Building to replace outmoded facilities
		60 PIs and 200 support staff
		170,000 sq ft: 85% research labs and 15% support


	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


	SnB Software by UB/HWI
		“Top Algorithms of the Century”
	Critical to Rational Drug Design
	Important Link in Structural Biology


	Vancomycin solved with SnB
		“Antibiotic of Last Resort”
		Original molecular structure required 5 months of computing to solve
		(Re)solved in a single day on CCR’s supercomputers


	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.


	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 Reconstruction of CT Dataset
	Created with the Visualization Toolkit (VTK) on a Linux Workstation
	3D Isosurface Clearly Shows Structure that is Nearly Impossible to Determine from 2D Slices


	3D Reconstruction of an Oral Epithelial Cell
	Translucent White Surface Represents the Cell Membrane
	Reddish Surface Represents Groups of Bacteria


	Leading U.S. Academic Supercomputing Center
		High-Performance Computing
		High-End Visualization
	Support ~80 Groups in ~25 Depts
	Education/Outreach/Training
		H.S. Summer Program
		Work with Local Industry & Local Colleges
		Hosts Meetings/Provides Tours
		M.S. Certificate Program in Computational Science


	Structural Biology
		Molecular Structure Determination & DNA Sequence Analysis
	Protein Folding
		Computer simulations determine the 3D structure of proteins.
	Environmentally Friendly Solvents
		Study supercritical CO₂ as a solvent to reduce the need for toxic solvents.
	Groundwater Modeling
		Predict contaminant flow in groundwater & migration into streams and lakes.
	Industrial Design Optimization
		Design, modify, and perfect new products at reduced cost.
	Fluid Dynamics
		Modeling turbulent flows and combustion in order to improve design of chemical reactors, turbine engines, and airplanes.
	Volcanology
		Study of volcanoes for risk assessment. Modeling of lava flows and mudslides.


	Financial Analysis
		Datamining analaysis for prediction.
	Dental Implant Design
		Simulation and modeling of a dental implant in a jawbone to reduce failure rate.
	Physiology
		Flow & regulation in kidney. Flow altered by aneurysm.
	Biophysics
		Measure protein conformational dynamics.
	Visualization & Multimedia
		Peace Bridge, Buffalo Medical Corridor, CCR, Events. Networked media. Art.
	Semiconductor Manufacturing
		New processes & chemicals to improve the manufacturing of computer chips.
	Classics
		Digital reconstruction of Assyrian Palace.


	SGI Origin2000
		128 Processors (250 MHz)
		32 GB RAM
		400 GB Fibre Channel Disk Storage
	IBM RS/6000 SP
		78 Processors
		26 GB Ram, 640 GB Disk Storage
	Sun Microsystems Cluster
		48 Sun Ultra 5 Workstations (333MHz)
		32 Sunblades (750MHz)
		Myrinet + 100BT Ethernet
	SGI Intel Linux Cluster
		150 Pentium III Processors (1 GHz)
		75 GB RAM, 2.5 TB Disk Storage
		Myrinet2000 + 100BT Ethernet


	Manufacturing
	Medical Imaging
	Computational Science
	Simulation & Modeling
	Historical Reenactments
	Multimedia Presentations


	Hardware
		Cluster Computing: 2-6TFlops
		ACCESS Grid
		Commodity Viz Clusters
		Portable Viz Systems
		Additional Viz Workbench
		Commodity Projection Systems
	Software
		Bioinformatics
		Modeling and Simulation Packages
		Database & Data Mining
		Storage Management