Living in a World of Nanobioinfotechnology

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07.09.12
Invited Talk
Invitrogen
Title: Living in a World of Nanobioinfotechnology
Carlsbad, CA

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  • Living in a World of Nanobioinfotechnology

    1. 1. 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
    2. 2. California’s Institutes for Science and Innovation A Bold Experiment in Collaborative Research California NanoSystems Institute UCSF UCB California Institute for Bioengineering, Biotechnology, and Quantitative Biomedical Research California Institute for Telecommunications and Information Technology Center for Information Technology Research in the Interest of Society UCSC UCD UCM www.ucop.edu/california-institutes UCSB UCLA UCI UCSD
    3. 3. Two New Calit2 Buildings Provide New Laboratories for “Living in the Future” <ul><li>“ Convergence” Laboratory Facilities </li></ul><ul><ul><li>Nanotech, BioMEMS, Chips, Radio, Photonics </li></ul></ul><ul><ul><li>Virtual Reality, Digital Cinema, HDTV, Gaming </li></ul></ul><ul><li>Over 1000 Researchers from 24 Departments </li></ul><ul><ul><li>Buildings Linked via Dedicated Optical Networks </li></ul></ul>UC Irvine www.calit2.net Preparing for a World in Which Distance is Eliminated… UC San Diego
    4. 4. Federal Agencies Have Funded $350 Million to Over 300 Calit2 Affiliated Grants Federal Agency Source of Funds Creating a Rich Ecology of Basic Research 50 Grants Over $1 Million Broad Distribution of Medium and Small Grants
    5. 5. In Spite of the Bubble Bursting, Calit2 Has Partnered with over 130 Companies Industrial Partners > $1 Million Over $80 Million From Industry So Far Broad Range of Companies More Than 80 Have Provided Funds or In-kind
    6. 6. Accelerator: The Perfect Storm-- Convergence of Engineering with Bio, Physics, & IT 2 mm HP MemorySpot Nanobio info technology 1000x Magnification MEMS 2 micron DNA-Conjugated Microbeads Human Adenovirus 400x Magnification NANO IBM Quantum Corral Iron Atoms on Copper 5 nanometers 400,000 x !
    7. 7. Calit2 is Creating a Nano-Bio-Info Innovation Laboratory Donald Bren School of Information and Computer Science
    8. 8. INRF Supports Researchers in Nano and BioMEMS BioMEMS and Medical Applications Nanotechnology / Nanofabrication Spray atomization of nano powders New methods of making arrays of nanowires Boron-based nanowires for novel circuits Carbon nanotubes for sensor and electronic applications Micromirror on a catheter for optical biopsy using coherence tomography Protein crystallization in nanovolumes 0 ms 200 ms 400 ms 600 ms Microfluidic devices for electrophoretic separations Microfluidic devices using droplets, CD microfluidics and magnetohydrodynamics
    9. 9. INRF Partners Companies with University Researchers: 70 Past and Current Collaborating Companies <ul><li>Advanced Customs Sensors Inc. </li></ul><ul><li>Agilient </li></ul><ul><li>Alpha Industry/Network Device Inc. </li></ul><ul><li>AXT/Alpha Photonics Incorporated </li></ul><ul><li>Alpine Microsystems Incorporated </li></ul><ul><li>Auxora, Inc. </li></ul><ul><li>Bethel Material Research </li></ul><ul><li>Broadcom </li></ul><ul><li>Broadley-James Corp. </li></ul><ul><li>Cito Optronics, Inc. </li></ul><ul><li>Coherent, Inc. </li></ul><ul><li>Conexant </li></ul><ul><li>Coventor </li></ul><ul><li>DRS Sensors </li></ul><ul><li>Endevco Friends USA </li></ul><ul><li>General Monitors </li></ul><ul><li>Global Communication Semiconductor </li></ul><ul><li>Hewlett Packard </li></ul><ul><li>Hitachi Chemical Research </li></ul><ul><li>IJ Research </li></ul><ul><li>Impco Technology </li></ul><ul><li>Intelligent Epitaxy Incorporated </li></ul><ul><li>International Technology Works </li></ul><ul><li>IOS </li></ul><ul><li>Irvine Sensors </li></ul><ul><li>Jazz Semiconductor </li></ul><ul><li>Linfinity Microelectronics </li></ul><ul><li>Maxwell Sensors </li></ul><ul><li>Metrolaser Incorporated Microtek Lab Incorporated </li></ul><ul><li>MicroWave Technology </li></ul><ul><li>Moog, Inc. </li></ul><ul><li>Network Device </li></ul><ul><li>Newport Opticom </li></ul><ul><li>NexGen Research Corporation </li></ul><ul><li>Northrop Grumman Corporation </li></ul><ul><li>Numerical Technologies Ormet Corp. </li></ul><ul><li>Oplink Communications </li></ul><ul><li>Optical Crossing </li></ul><ul><li>Optinetrics </li></ul><ul><li>Optiswitch Technology </li></ul><ul><li>Physical Optics Corp. </li></ul><ul><li>Printronix </li></ul><ul><li>ProComm Enterprises </li></ul><ul><li>Rainbow Communications </li></ul><ul><li>Raytheon Systems </li></ul><ul><li>Rockwell </li></ul><ul><li>RF Integrated Corp. </li></ul><ul><li>Sabeus Photonics </li></ul><ul><li>Saddleback Aerospace </li></ul><ul><li>SAIC Second Sight, LLC </li></ul><ul><li>Semco Laser Technology </li></ul><ul><li>Sequenom </li></ul><ul><li>Silicon Storage Technology, Inc. </li></ul><ul><li>Simax </li></ul><ul><li>Skyworks Solutions </li></ul><ul><li>SVT Associates </li></ul><ul><li>Tamarack Scientific, Inc. </li></ul><ul><li>Tanner Research, Inc. </li></ul><ul><li>Texas Instruments, Inc. </li></ul><ul><li>TRW </li></ul><ul><li>U Machines </li></ul><ul><li>Versa Technology </li></ul><ul><li>VSK Photonics </li></ul><ul><li>WIN Semiconductors </li></ul><ul><li>Xtal Technologies </li></ul><ul><li>Y Media Corporation </li></ul>40 UCI Faculty from a Dozen Departments
    10. 10. Calit2@UCI Nanobioinfotechnology “Innovation Pipeline” INRF Calit2 BiON Zeiss Center of Excellence Micro/Nano Materials and Devices Bio-Organic Nano Lab SEM, Advanced Characterization Three centers share a common infrastructure Photonics, RF, Chip Labs Integrate with Chips, Telecom Source: GP Li, Calit2
    11. 11. Example: Real-Time Electronic Readout from Single Biomolecule Sensors <ul><li>Carbon Nanotube Circuits Provide Nanoscale Connectivity </li></ul><ul><li>New Techniques Integrate Single-Molecule Attachments </li></ul><ul><li>Dynamics and Interactions With the Environment Can be Directly Measured </li></ul><ul><li>Electronic Readout Compatible With Hand-held, Low-power Devices </li></ul>Source: Phil Collins & Greg Weiss, Calit2@UCI 1 nm wiring 1 protein molecule … and without device in buffer with reagents Schematic & SEM Image of Carbon Nanotube-based Device
    12. 12. Lifechips--Merging Two Major Industries: Microelectronic Chips & Life Sciences LifeChips: the merging of two major industries, the microelectronic chip industry with the life science industry LifeChips medical devices 65 UCI Faculty
    13. 13. Calit2@UCSD Building Anchors “Bio-Nano-IT Convergence Quad” Calit2 Bioengineering Computer Science and Engineering
    14. 14. UCSD Jacobs School of Engineering NanoEngineering Department Proposal Proponents Faculty Leadership Team Sadik Esener Dept. of Electrical and Computer Engineering Michael Heller Dept. of Bioengineering Sungho Jin Dept. of Mechanical and Aerospace Engineering Jan Talbot Dept. of Mechanical and Aerospace Engineering - Chemical Engineering Program 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
    15. 15. Calit2 Nano3 Clean Rooms Helps “Jump Start” The New Jacobs School Dept. of Nanoengineering Nano3 Facility CALIT2.UCSD 10,000 sq. feet State-of-the-Art Materials and Devices Laboratory Source: Bernd Fruhberger, Calit2 http://nano3.calit2.net/ 45 Faculty with Nano Projects at Calit2@UCSD
    16. 16. Yu-Hwa Lo Research Group Electrical and Computer Engineering 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
    17. 17. Treatment, Understanding, and Monitoring of Cancer (UCSD, Burnham Institute, UCSB, UCR, UCI --PI: Sadik Esener)
    18. 18. Nano-Structured Porous Silicon Applied to Cancer Treatment Michael J. Sailor Research Group Chemistry and Biochemistry Nanostructured “Mother Ships” for delivery of cancer therapeutics. Nanodevices for In-vivo Detection & Treatment of Cancerous Tumors Porous Photonic Crystals for Cell-based Biosensor Human epithelial (HeLa) cells on a photonic crystal. The colors observed can be used to monitor the physiological status of the cells.
    19. 19. 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 100 nm 100 nm Silica gel wall 5 nm thick 100 nm cavity
    20. 20. Cancer Nanotechnology Kummel / Trogler / Schuller Cancer Center Project Single Cancer Cell Isolated on Engineered Surface for Phenotyping and Genotyping Hoechst Nuclear Stain (Blue), Nano-bead Membrane Dye (Green), Surface AttachmentSite (Red). Devices for Fast and Automated Detection of Single Cancer Cells in Tissue Margins Advanced Staining Procedures Allows Us to Distinguish Epithelial Cells (Cancerous) From Non-Epithelial Cells Developing Small Molecule and Quantum Dot Cell Staining Procedures to Identify Single Cancer Cells in Otherwise Normal Tissue Green : Cancer Specific Stain II Red : Cancer Specific Stain I Blue : Hoechst Nucleus Stain Finding the Needle in the Haystack
    21. 21. Quantum Dot Staining of Filled Cells: Light Microscopy astro volume (gray); perimeter cx43 (red); internal cx43 (yellow) 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 Immuno-Labelling of Cx43 with Quantum Dots Allows for Correlated LM and EM of cx43 on the Dye-Filled Astrocyte. Source: B. Smarr, M. Ellisman, UCSD NCMIR
    22. 22. Calit2 Brings Computer Scientists and Engineers Together with Biomedical Researchers <ul><li>Some Areas of Concentration: </li></ul><ul><ul><li>Algorithmic and System Biology </li></ul></ul><ul><ul><li>Bioinformatics </li></ul></ul><ul><ul><li>Metagenomics </li></ul></ul><ul><ul><li>Cancer Genomics </li></ul></ul><ul><ul><li>Human Genomic Variation and Disease </li></ul></ul><ul><ul><li>Proteomics </li></ul></ul><ul><ul><li>Mitochondrial Evolution </li></ul></ul><ul><ul><li>Computational Biology </li></ul></ul><ul><ul><li>Multi-Scale Cellular Imaging </li></ul></ul><ul><ul><li>Information Theory and Biological Systems </li></ul></ul><ul><ul><li>Telemedicine </li></ul></ul>UC Irvine UC Irvine Southern California Telemedicine Learning Center (TLC) National Biomedical Computation Resource an NIH supported resource center
    23. 23. Calit2 Facilitated Formation of the Center for Algorithmic and Systems Biology http://casb.ucsd.edu/
    24. 24. UCI’s IGB Develops a Suite of Programs and Servers for Protein Structure and Structural Feature Prediction www.igb.uci.edu/tools.htm Source: Pierre Baldi, UCI Sixty Affiliated IGB Labs at UCI e.g.:
    25. 25. Information Theorists Working with Bio, IT, and Nano Researchers Will Radically Transform Our View of Living Systems &quot;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 Loewenstein The Touchstone of Life (1999) Calit2’s Information Theory and Applications Center http://ita.ucsd.edu
    26. 26. PI Larry Smarr Paul Gilna Ex. Dir. Announced January 17, 2006 $24.5M Over Seven Years
    27. 27. Marine Genome Sequencing Project – Measuring the Genetic Diversity of Ocean Microbes Sorcerer II Data Will Double Number of Proteins in GenBank! Plus 155 Marine Microbial Genomes Specify Ocean Data Each Sample ~2000 Microbial Species
    28. 28. Enormous Increase in Scale of Known Genes Over Last Decade 6.3 Billion Bases 5.6 Million Genes 1.8 Million Bases 1749 Genes ~3300x 1995 First Microbe Genome 2007 Ocean Microbial Metagenomics
    29. 29. CAMERA 1.1 is Up and Running!
    30. 30. Can We Create a “Facebook” for Science Researchers? Microbial Metagenomics as a Cyber-Community 1300 Registered CAMERA Users From 45 Countries
    31. 31. From Microbial Genomes To Human Disease <ul><li>Microbes Have a Much Simpler Genome Than Humans </li></ul><ul><li>However, Microbes Share Many of the Core Components of the Molecular Signaling Machinery Used by Humans </li></ul><ul><li>Understand Both the Evolution and Regulation of Signaling Systems, First in Microbes and Then in Humans </li></ul><ul><li>We Illustrate This Using the Protein Kinase Superfamily That is Implicated in Numerous Human Diseases </li></ul>Source: Susan Taylor, SOM, UCSD Identified 15,000 New Kinases In Venter Global Ocean Sampling Data
    32. 32. Medically Relevant Metagenomic Data Sets Are Rapidly Being Accumulated <ul><li>“ A majority of the bacterial sequences corresponded to uncultivated species and novel microorganisms.” </li></ul><ul><li>“ We discovered significant inter-subject variability.” </li></ul><ul><li>“ Characterization of this immensely diverse ecosystem is the first step in elucidating its role in health and disease.” </li></ul>“ Diversity of the Human Intestinal Microbial Flora” Paul B. Eckburg, et al Science (10 June 2005) 395 Phylotypes
    33. 33. Full Genome Sequencing is Exploding: Most Sequenced Genomes are Bacterial www.genomesonline.org >100 Metagenomes First Genome 1995 6 Genomes/ Year 2000 1600 Genomes 2007
    34. 34. 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
    35. 35. DOE Genomic Encyclopedia of Bacteria and Archaea (GEBA) / Bergey Solution: Deep Sampling Across Phyla Source: Eddie Rubin, DOE JGI 2007 Goal: Finish ~100 Bacterial and Archaeal Genomes from Culture Collections Project Lead -- Jonathan Eisen (JGI/UC Davis) Acidobacteria Bacteroides Fibrobacteres Gemmimonas Verrucomicrobia Planctomycetes Chloroflexi Proteobacteria Chlorobi Firmicutes Fusobacteria Actinobacteria Cyanobacteria Chlamydia Spriochaetes Deinococcus-Thermus Aquificae Thermotogae TM6 OS-K Termite Group OP8 Marine GroupA WS3 OP9 NKB19 OP3 OP10 TM7 OP1 OP11 Nitrospira Synergistes Deferribacteres Thermudesulfobacteria Chrysiogenetes Thermomicrobia Dictyoglomus Coprothmermobacter Well sampled phyla No cultured taxa
    36. 36. The Bioinformatics Core of the Joint Center for Structural Genomics is Housed in the Calit2@UCSD Building Extremely Thermostable -- Useful for Many Industrial Processes (e.g. Chemical and Food) 173 Structures (122 from JCSG) <ul><ul><li>Determining the Protein Structures of the Thermotoga Maritima Genome </li></ul></ul><ul><ul><li>122 T.M. Structures Solved by JCSG (75 Unique In The PDB) </li></ul></ul><ul><ul><li>Direct Structural Coverage of 25% of the Expressed Soluble Proteins </li></ul></ul><ul><ul><li>Probably Represents the Highest Structural Coverage of Any Organism </li></ul></ul>Source: John Wooley, UCSD
    37. 37. Interactive Exploration of the Proteins of the Marine Microbe Thermatoga
    38. 38. Building Genome-Scale Models of Living Organisms <ul><li>E. Coli </li></ul><ul><ul><li>Has 4300 Genes </li></ul></ul><ul><ul><li>Model Has 2000! </li></ul></ul>Source: Bernhard Palsson UCSD Genetic Circuits Research Group http://gcrg.ucsd.edu JTB 2002 JBC 2002 <ul><li>in Silico Organisms Now Available 2007: </li></ul><ul><li>Escherichia coli </li></ul><ul><li>Haemophilus influenzae </li></ul><ul><li>Helicobacter pylori </li></ul><ul><li>Homo sapiens Build 1 </li></ul><ul><li>Human red blood cell </li></ul><ul><li>Human cardiac mitochondria </li></ul><ul><li>Methanosarcina barkeri </li></ul><ul><li>Mouse Cardiomyocyte </li></ul><ul><li>Mycobacterium tuberculosis </li></ul><ul><li>Saccharomyces cerevisiae </li></ul><ul><li>Staphylococcus aureus </li></ul>
    39. 39. Biochemically, Genetically and Genomically (BiGG) Genome-Scale Metabolic Reconstructions H. influenzae H. pylori S. aureus S. typhimurium <ul><li>M. barkeri </li></ul><ul><li>619 Reactions </li></ul><ul><li>692 Genes </li></ul><ul><li>S. cerevisiae </li></ul><ul><li>1402 Reactions </li></ul><ul><li>910 Genes </li></ul><ul><li>E. coli </li></ul><ul><li>2035 Reactions </li></ul><ul><li>1260 Genes </li></ul><ul><li>S. aureus </li></ul><ul><li>640 Reactions </li></ul><ul><li>619 Genes </li></ul><ul><li>Mitoc. </li></ul><ul><li>218 Rxns </li></ul><ul><li>H. sapiens </li></ul><ul><li>3311 Reactions </li></ul><ul><li>1496 Genes </li></ul><ul><li>S. typhimurium </li></ul><ul><li>898 Reactions </li></ul><ul><li>826 Genes </li></ul><ul><li>H. pylori </li></ul><ul><li>558 Reactions </li></ul><ul><li>341 Genes </li></ul><ul><li>H. influenzae </li></ul><ul><li>472 Reactions </li></ul><ul><li>376 Genes </li></ul><ul><li>M. tuberculosis </li></ul><ul><li>939 Reactions </li></ul><ul><li>661 Genes </li></ul>Systems Biology Research Group http://systemsbiology.ucsd.edu <ul><li>RBC </li></ul><ul><li>39 Rxns </li></ul>
    40. 40. With Nanobioinfo Devices Everywhere, How Can We Handle the Data Flows? <ul><li>Mobile Broadband </li></ul><ul><ul><li>0.1-0.5 Mbps </li></ul></ul><ul><li>Home Broadband </li></ul><ul><ul><li>1-5 Mbps </li></ul></ul><ul><li>University Dorm Room Broadband </li></ul><ul><ul><li>10-100 Mbps </li></ul></ul><ul><li>Calit2 Global Broadband </li></ul><ul><ul><li>1,000-10,000 Mbps </li></ul></ul>100,000 Fold Range All Here Today! “ The future is already here, it’s just not evenly distributed” William Gibson, Author of Neuromancer
    41. 41. The OptIPuter Project: Defining a High Performance Collaboration Infrastructure for Eng-Med Picture Source: Mark Ellisman, David Lee, Jason Leigh Calit2 (UCSD, UCI) and UIC Lead Campuses—Larry Smarr PI Univ. Partners: SDSC, USC, SDSU, NW, TA&M, UvA, SARA, KISTI, AIST Industry: IBM, Sun, Telcordia, Chiaro, Calient, Glimmerglass, Lucent $13.5M Over Five Years Scalable Adaptive Graphics Environment (SAGE)
    42. 42. My OptIPortal TM – Affordable Termination Device for the OptIPuter Global Backplane <ul><li>20 Dual CPU Nodes, Twenty 24” Monitors, ~$50,000 </li></ul><ul><li>1/4 Teraflop, 5 Terabyte Storage, 45 Mega Pixels--Nice PC! </li></ul><ul><li>Scalable Adaptive Graphics Environment ( SAGE) Jason Leigh, EVL-UIC </li></ul>Source: Phil Papadopoulos SDSC, Calit2
    43. 43. OptIPuter Scalable Displays Are Used for Multi-Scale Biomedical Imaging Green: Purkinje Cells Red: Glial Cells Light Blue: Nuclear DNA Source: Mark Ellisman, David Lee, Jason Leigh Two-Photon Laser Confocal Microscope Montage of 40x36=1440 Images in 3 Channels of a Mid-Sagittal Section of Rat Cerebellum Acquired Over an 8-hour Period 200 Megapixels!
    44. 44. Scalable Displays Allow Both Global Content and Fine Detail
    45. 45. Allows for Interactive Zooming from Cerebellum to Individual Neurons
    46. 46. Interactive Exploration of Marine Genomes Using 100 Million Pixels Ginger Armburst (UW), Terry Gaasterland (UCSD SIO)
    47. 47. Nearly One Half Billion Pixels in Calit2 Extreme Visualization Project! Connected at 2,000 Megabits/s! UC Irvine UC San Diego UCI HIPerWall Analyzing Pre- and Post- Katrina Falko Kuester, UCSD; Steven Jenks, UCI
    48. 48. An Emerging High Performance Collaboratory for Microbial Metagenomics NW! CICESE UW JCVI MIT SIO UCSD SDSU UIC EVL UCI OptIPortals OptIPortal UC Davis UMich
    49. 49. 3D OptIPortal Calit2 StarCAVE Telepresence “Holodeck” 60 GB Texture Memory, Renders Images 3,200 Times the Speed of Single PC Source: Tom DeFanti, Greg Dawe, Calit2 Connected at 200 Gb/s 30 HD Projectors!
    50. 50. Countries are Aggressively Creating Gigabit Services: Interactive Access to CAMERA Data System www.glif.is Created in Reykjavik, Iceland 2003 Visualization courtesy of Bob Patterson, NCSA.

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