Living in a World of Nanobioinfotechnology

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Living in a World of Nanobioinfotechnology

• Invited Talk
• Invitrogen
• Carlsbad, CA
• September 12, 2007

Dr. Larry Smarr Director, California Institute
for Telecommunications and Information
Technology Harry E. Gruber Professor, Dept. of
Computer Science and Engineering Jacobs School of
Engineering, UCSD
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Californias Institutes for Science and
Innovation A Bold Experiment in Collaborative
Research
California Institute for Bioengineering,
Biotechnology, and Quantitative Biomedical
Research
Center for Information Technology Research in
the Interest of Society
UCD
UCM
UCB
UCSF
California NanoSystems Institute
UCSC
California Institute for Telecommunications and
Information Technology
www.ucop.edu/california-institutes
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Two New Calit2 Buildings Provide New
Laboratories for Living in the Future

• Convergence Laboratory Facilities
• Nanotech, BioMEMS, Chips, Radio, Photonics
• Virtual Reality, Digital Cinema, HDTV, Gaming
• Over 1000 Researchers from 24 Departments
• Buildings Linked via Dedicated Optical Networks

UC Irvine
www.calit2.net
Preparing for a World in Which Distance is
Eliminated
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Federal Agencies Have Funded 350 Million to
Over 300 Calit2 Affiliated Grants
50 Grants Over 1 Million
Broad Distribution of Medium and Small Grants
Creating a Rich Ecology of Basic Research
Federal Agency Source of Funds
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In Spite of the Bubble Bursting, Calit2 Has
Partnered with over 130 Companies
Over 80 Million From Industry So Far
Industrial Partners gt 1 Million
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Accelerator The Perfect Storm-- Convergence of
Engineering with Bio, Physics, IT
HP MemorySpot
2 mm
Nanobioinfotechnology
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Calit2 is Creating a Nano-Bio-Info Innovation
Laboratory
Donald Bren School of Information and Computer
Science
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INRF Supports Researchers in Nano and BioMEMS
Nanotechnology / Nanofabrication
BioMEMS and Medical Applications
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INRF Partners Companies with University
Researchers 70 Past and Current Collaborating
Companies

• Advanced Customs Sensors Inc.
• Agilient
• Alpha Industry/Network Device Inc.
• AXT/Alpha Photonics Incorporated
• Alpine Microsystems Incorporated
• Auxora, Inc.
• Bethel Material Research
• Broadcom
• Broadley-James Corp.
• Cito Optronics, Inc.
• Coherent, Inc.
• Conexant
• Coventor
• DRS Sensors
• EndevcoFriends USA
• General Monitors
• Global Communication Semiconductor
• Hewlett Packard
• Hitachi Chemical Research

• NexGen Research Corporation
• Northrop Grumman Corporation
• Numerical TechnologiesOrmet Corp.
• Oplink Communications
• Optical Crossing
• Optinetrics
• Optiswitch Technology
• Physical Optics Corp.
• Printronix
• ProComm Enterprises
• Rainbow Communications
• Raytheon Systems
• Rockwell
• RF Integrated Corp.
• Sabeus Photonics
• Saddleback Aerospace
• SAICSecond Sight, LLC
• Semco Laser Technology
• Sequenom

40 UCI Faculty from a Dozen Departments
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Calit2_at_UCI NanobioinfotechnologyInnovation
Pipeline
Photonics, RF, Chip Labs
ZeissCenter of Excellence
Calit2BiON
INRF
Integrate with Chips, Telecom
SEM,Advanced Characterization
Micro/Nano Materials and Devices
Bio-Organic Nano Lab
Three centers share a common infrastructure
Source GP Li, Calit2
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Example Real-Time Electronic Readout from
Single Biomolecule Sensors

• Carbon Nanotube Circuits Provide Nanoscale
  Connectivity
• New Techniques Integrate Single-Molecule
  Attachments
• Dynamics and Interactions With the Environment
  Can be Directly Measured
• Electronic Readout Compatible With Hand-held,
  Low-power Devices

1 nm wiring
1 protein molecule
Schematic SEM Image of Carbon Nanotube-based
Device
device in buffer with reagents
and without
Source Phil Collins Greg Weiss, Calit2_at_UCI
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Lifechips--Merging Two Major Industries
Microelectronic Chips Life Sciences
65 UCI Faculty
LifeChips the merging of two major industries,
the microelectronic chip industry with the life
science industry
LifeChips medical devices
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Calit2_at_UCSD Building Anchors Bio-Nano-IT
Convergence Quad
Calit2
Bioengineering
Computer Science and Engineering
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UCSD Jacobs School of Engineering NanoEngineering
Department Proposal Proponents
Faculty Leadership Team
Jan Talbot Dept. of Mechanical and Aerospace
Engineering - Chemical Engineering Program
Sadik Esener Dept. of Electrical and Computer
Engineering
Michael Heller Dept. of Bioengineering
Sungho Jin Dept. of Mechanical and
Aerospace Engineering
Kenneth Vecchio Dept. of Mechanical and
Aerospace Engineering
In the past five years alone, these five faculty
filed 51 patent applications and licensed 6
inventions to private companies
Corporate Supporters
GMT Ventures Invitrogen Pfizer Illumina
QUASAR Federal Systems ResMed Enterprise
Partners Venture Capital Varian Medical Systems
Sun Microsystems SAIC Intel
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Calit2 Nano3 Clean Rooms Helps Jump StartThe
New Jacobs School Dept. of Nanoengineering
Nano3 Facility CALIT2.UCSD
10,000 sq. feet State-of-the-Art Materials and
Devices Laboratory
45 Faculty with Nano Projects at Calit2_at_UCSD
http//nano3.calit2.net/
Source Bernd Fruhberger, Calit2
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Integrating Photonics and Microfluidics
Microfluidic Flow Cytometry Chip for Portable,
Low-cost Blood Analysis. The Chip Contains 12
Lenses and 6 Waveguides to Illuminate a Single
Cell and Collect the Light it Scatters
Yu-Hwa Lo Research Group Electrical and Computer
Engineering
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Treatment, Understanding, and Monitoring of
Cancer (UCSD, Burnham Institute, UCSB, UCR, UCI
--PI Sadik Esener)
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Nano-Structured Porous SiliconApplied to Cancer
Treatment
Nanodevices for In-vivo Detection Treatment of
Cancerous Tumors Porous Photonic Crystals for
Cell-based Biosensor
Nanostructured Mother Ships for delivery of
cancer therapeutics.
Human epithelial (HeLa) cells on a photonic
crystal. The colors observed can be used to
monitor the physiological status of the cells.
Michael J. Sailor Research Group Chemistry and
Biochemistry
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TEM Images of Hollow Silica Nanospheres for Drug
and Gene Delivery Applications
J. Yang, J. U. Lind, W. C. Trogler, Department
of Chemistry and Biochemistry and Calit2
Nanomedicine Laboratory
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Cancer NanotechnologyKummel / Trogler / Schuller
Cancer Center Project
Devices for Fast and Automated Detection
of Single Cancer Cells in Tissue Margins
Blue Hoechst Nucleus Stain
Finding the Needle in the Haystack
Red Cancer Specific Stain I
Green Cancer Specific Stain II
Developing Small Molecule and Quantum Dot Cell
Staining Procedures to Identify Single Cancer
Cells in Otherwise Normal Tissue
Single Cancer Cell Isolated on Engineered Surface
for Phenotyping and Genotyping Hoechst Nuclear
Stain (Blue), Nano-bead Membrane Dye (Green),
Surface AttachmentSite (Red).
Advanced Staining Procedures Allows Us to
Distinguish Epithelial Cells (Cancerous) From
Non-Epithelial Cells
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Quantum Dot Staining of Filled Cells Light
Microscopy
Source B. Smarr, M. Ellisman, UCSD NCMIR
Dye Filled Astrocytes in the Brain are
Immuno-Labeled with QDs for Connexin Proteins
(Cell-Borders in Yellow) Diffraction-Limit
Volumes Can Then be Acquired and the
Distribution of the Protein over the Cells Can
be Quantified and Analyzed
astro volume (gray) perimeter cx43 (red)
internal cx43 (yellow)
Immuno-Labelling of Cx43 with Quantum Dots Allows
for Correlated LM and EM of cx43 on the
Dye-Filled Astrocyte.
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Calit2 Brings Computer Scientists and Engineers
Together with Biomedical Researchers

• Some Areas of Concentration
• Algorithmic and System Biology
• Bioinformatics
• Metagenomics
• Cancer Genomics
• Human Genomic Variation and Disease
• Proteomics
• Mitochondrial Evolution
• Computational Biology
• Multi-Scale Cellular Imaging
• Information Theory and Biological Systems
• Telemedicine

UC Irvine
UC Irvine
Southern California Telemedicine Learning Center
(TLC)
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Calit2 Facilitated Formation of the Center for
Algorithmic and Systems Biology
http//casb.ucsd.edu/
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UCIs IGB Develops a Suite of Programs and
Servers for Protein Structure and Structural
Feature Prediction
Sixty Affiliated IGB Labs at UCI e.g.
www.igb.uci.edu/tools.htm
Source Pierre Baldi, UCI
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Information Theorists Working with Bio, IT, and
Nano Researchers Will Radically Transform Our
View of Living Systems
"Through the strong loupe of information theory,
we will be able to watch how such living
beings do what nonliving systems cannot do
extract information from their surrounds,
store it in a stable molecular form, and
eventually parcel it out for their creative
endeavors. ... So viewed, the information
circle becomes the unit of life. --Werner
LoewensteinThe Touchstone of Life (1999)
Calit2s Information Theory and Applications
Center http//ita.ucsd.edu
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Paul Gilna Ex. Dir.
PI Larry Smarr
Announced January 17, 2006 24.5M Over Seven Years
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Marine Genome Sequencing Project Measuring the
Genetic Diversity of Ocean Microbes
Plus 155 Marine Microbial Genomes
Sorcerer II Data Will Double Number of Proteins
in GenBank!
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Enormous Increase in Scale of Known Genes Over
Last Decade
1.8 Million Bases 1749 Genes
6.3 Billion Bases 5.6 Million Genes
3300x
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CAMERA 1.1 is Up and Running!
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Can We Create a Facebook for Science
Researchers? Microbial Metagenomics as a
Cyber-Community
1300 Registered CAMERA Users From 45 Countries
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From Microbial Genomes To Human Disease

• Microbes Have a Much Simpler Genome Than Humans
• However, Microbes Share Many of the Core
  Components of the Molecular Signaling Machinery
  Used by Humans
• Understand Both the Evolution and Regulation of
  Signaling Systems, First in Microbes and Then in
  Humans
• We Illustrate This Using the Protein Kinase
  Superfamily That is Implicated in Numerous Human
  Diseases

Identified 15,000 New Kinases In Venter Global
Ocean Sampling Data
Source Susan Taylor, SOM, UCSD
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Medically Relevant Metagenomic Data SetsAre
Rapidly Being Accumulated

• A majority of the bacterial sequences
  corresponded to uncultivated species and novel
  microorganisms.
• We discovered significant inter-subject
  variability.
• Characterization of this immensely diverse
  ecosystem is the first step in elucidating its
  role in health and disease.

395 Phylotypes
Diversity of the Human Intestinal Microbial
Flora Paul B. Eckburg, et al Science (10 June
2005)
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Full Genome Sequencing is ExplodingMost
Sequenced Genomes are Bacterial
First Genome 1995 6 Genomes/ Year 2000 1600
Genomes 2007
gt100 Metagenomes
www.genomesonline.org
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Moore Foundation Funded the Venter Institute to
Provide the Full Genome Sequence of 155 Marine
Microbes
Phylogenetic Trees Created by Uli Stingl, Oregon
State Blue Means Contains One of the Moore 155
Genomes
www.moore.org/microgenome/trees.aspx
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DOE Genomic Encyclopedia of Bacteria and Archaea
(GEBA) / Bergey Solution Deep Sampling Across
Phyla
2007 Goal Finish 100 Bacterial and Archaeal
Genomes from Culture Collections Project Lead --
Jonathan Eisen (JGI/UC Davis)
Source Eddie Rubin, DOE JGI
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The Bioinformatics Core of the Joint Center for
Structural Genomics is Housed in the Calit2_at_UCSD
Building
Extremely Thermostable -- Useful for Many
Industrial Processes (e.g. Chemical and Food)
173 Structures (122 from JCSG)

• Determining the Protein Structures of the
  Thermotoga Maritima Genome
• 122 T.M. Structures Solved by JCSG (75 Unique In
  The PDB)
• Direct Structural Coverage of 25 of the
  Expressed Soluble Proteins
• Probably Represents the Highest Structural
  Coverage of Any Organism

Source John Wooley, UCSD
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Interactive Exploration of the Proteins of the
Marine Microbe Thermatoga
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Building Genome-Scale Models of Living Organisms

• E. Coli
• Has 4300 Genes
• Model Has 2000!

JTB 2002
JBC 2002

• in Silico Organisms Now Available2007
• Escherichia coli
• Haemophilus influenzae
• Helicobacter pylori
• Homo sapiens Build 1
• Human red blood cell
• Human cardiac mitochondria
• Methanosarcina barkeri
• Mouse Cardiomyocyte
• Mycobacterium tuberculosis
• Saccharomyces cerevisiae
• Staphylococcus aureus

Source Bernhard Palsson UCSD Genetic Circuits
Research Group http//gcrg.ucsd.edu
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Biochemically, Genetically and Genomically (BiGG)
Genome-Scale Metabolic Reconstructions

• S. aureus
• 640 Reactions
• 619 Genes

• M. barkeri
• 619 Reactions
• 692 Genes

• H. sapiens
• 3311 Reactions
• 1496 Genes

• S. typhimurium
• 898 Reactions
• 826 Genes

• Mitoc.
• 218 Rxns

S. aureus
S. typhimurium
H. influenzae
H. pylori

• E. coli
• 2035 Reactions
• 1260 Genes

• H. pylori
• 558 Reactions
• 341 Genes

• S. cerevisiae
• 1402 Reactions
• 910 Genes

• M. tuberculosis
• 939 Reactions
• 661 Genes

• H. influenzae
• 472 Reactions
• 376 Genes

Systems Biology Research Group http//systemsbiolo
gy.ucsd.edu
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With Nanobioinfo Devices Everywhere, How Can We
Handle the Data Flows?

• Mobile Broadband
• 0.1-0.5 Mbps
• Home Broadband
• 1-5 Mbps
• University Dorm Room Broadband
• 10-100 Mbps
• Calit2 Global Broadband
• 1,000-10,000 Mbps

The future is already here, its just not
evenly distributedWilliam Gibson, Author of
Neuromancer
100,000 Fold Range All Here Today!
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The OptIPuter Project Defining a High
Performance Collaboration Infrastructure for
Eng-Med
Scalable Adaptive Graphics Environment (SAGE)
13.5M Over Five Years
Picture Source Mark Ellisman, David Lee, Jason
Leigh
Calit2 (UCSD, UCI) and UIC Lead CampusesLarry
Smarr PI Univ. Partners SDSC, USC, SDSU, NW,
TAM, UvA, SARA, KISTI, AIST Industry IBM, Sun,
Telcordia, Chiaro, Calient, Glimmerglass, Lucent
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My OptIPortalTM AffordableTermination Device
for the OptIPuter Global Backplane

• 20 Dual CPU Nodes, Twenty 24 Monitors, 50,000
• 1/4 Teraflop, 5 Terabyte Storage, 45 Mega
  Pixels--Nice PC!
• Scalable Adaptive Graphics Environment ( SAGE)
  Jason Leigh, EVL-UIC

Source Phil Papadopoulos SDSC, Calit2
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OptIPuter Scalable Displays Are Used for
Multi-Scale Biomedical Imaging
200 Megapixels!
Source Mark Ellisman, David Lee, Jason Leigh
Green Purkinje Cells Red Glial Cells Light
Blue Nuclear DNA
Two-Photon Laser Confocal Microscope Montage of
40x361440 Images in 3 Channels of a Mid-Sagittal
Section of Rat Cerebellum Acquired Over an 8-hour
Period
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Scalable Displays Allow Both Global Content and
Fine Detail
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Allows for Interactive Zooming from Cerebellum
to Individual Neurons
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Interactive Exploration of Marine Genomes Using
100 Million Pixels
Ginger Armburst (UW), Terry Gaasterland (UCSD SIO)
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Nearly One Half Billion Pixelsin Calit2 Extreme
Visualization Project!
UC San Diego
Connected at 2,000 Megabits/s!
UC Irvine
UCI HIPerWall Analyzing Pre- and Post- Katrina
Falko Kuester, UCSD Steven Jenks, UCI
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An Emerging High Performance Collaboratoryfor
Microbial Metagenomics
OptIPortals
UW
UMich
NW!
UIC EVL
MIT
UC Davis
JCVI
UCI
UCSD
SIO
OptIPortal
SDSU
CICESE
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3D OptIPortal Calit2 StarCAVE Telepresence
Holodeck
Source Tom DeFanti, Greg Dawe, Calit2
Connected at 200 Gb/s
30 HD Projectors!
60 GB Texture Memory, Renders Images 3,200 Times
the Speed of Single PC
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Countries are Aggressively Creating Gigabit
ServicesInteractive Access to CAMERA Data System
Visualization courtesy of Bob Patterson, NCSA.
www.glif.is Created in Reykjavik, Iceland 2003