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Designer Biology & Minimal Genome ‘OM’ICS • • • • • • • • Genomics Transcriptomics Proteomics Metablomics Cellomics Nutriomics Phenomics Pharmacogenomics Multidisciplinary • • • • • Artists engineering, chemistry, computer science, and molecular biology How does a Gene work? Adventures in Synthetic Biology Synthetic Biology is A) the design and construction of new biological parts, devices, and systems, and B) the re-design of existing, natural biological systems for useful purposes. Vision • rational assembly/ design of complex biologic systems by providing the foundations for classic engineering strategies Strategies • to limit the impact of manipulation of selected parts on the rest of the system, • strategies and parts to control complex system assemblies, such as genetic circuits; • providing the functional parts to implement artificial designs, e.g., obtained from freely re-assembling protein domains such as in polyketide synthesis • research to provide the technology for the implementation of complex system designs in the laboratory, • such as large scale de novo DNA design and the integration of complex protocols on microfluidic chips. Tools • • • • • • manipulating genes for decades; inserting, deleting, and changing them in various microbes Scissors- Restriction Enzymes Joining- Ligases Most Important Tools • • • • • • • RNA Regulation of gene expression Protein Ability to interact with small molecules Antisense technologies Plasmids E.coli- Favourite organism to manipulate Challenges for Synthetic Biology • • • • sustainable energy, protecting human health, creating new materials, and revealing the origin & fate of the universe Scope – Is it really defined for SB? • • • • Designing and constructing novel organisms biologically-inspired systems – or redesigning existing organisms and systems – to solve problems that natural systems cannot. Potential Scope BIODESIGN INDIA 1.0; October 8, 2010 Genetic Circuits An engineered cell Initiatives • • • • • • OpenWetWare Synthetic Genomics Study BioBricks The BioBricks Foundation Registry of Standard Biological Parts SynBERC Standard Part Registry • gene expression-based devices • i.e., PoPS, or polymerase per second (a term for quantifying the input/output signals in genetic circuits); • specifications for hierarchies for the Protein:DNA Parts (PDP) • Post-Translational Parts (PTP) families; • the first specification datasheet for a biological device. Projects • E. coli Automatic Directed Evolution Machine (E.ADEM) project • Engineering the Host/System Interface • Minimal Cell Project (MCP) • Rebuilding T7 • Synthetic E. coli genome project • Synthetic Mycoplasma genome project • Synthetic yeast genome project www.synbio.org Evolution is greater than God • automatically created, • from promoters, regulators, receptors, binding partners, enzymes and ribozymes, to sensors, logic devices, reporters, metabolic pathways, entire genomes, • and even solutions of mathematic problems. BIODESIGN INDIA 1.0; October 8, 2010 USA Source: www.synbioproject.org BIODESIGN INDIA 1.0; October 8, 2010 Source: www.synbioproject.org BIODESIGN INDIA 1.0; October 8, 2010 BIODESIGN INDIA 1.0; October 8, 2010 • • • • • • • • • • Biodream machines Synthetic Biology Designer Genome Computational Designs Playing God Hand made Biology Extreme Engineering Complexity of simplicity Custom made Tailor made Various Facets Information Reductionist Approach BIODESIGN INDIA 1.0; October 8, 2010 Craig Venter • Cynthia/Synthia • Mycoplasma laboratorium • I plan to show that we understand the software of life by creating true artificial life. And in this way I want to discover whether a life decoded is truly a life understood. • – A Life Decoded Craig Venter’s Synthia • • • • • • • • • • • • • Mycoplasma mycoides JCV1-syn1.0 "the first species.... to have its parents be a computer” Introduced in Mycoplasma capricolum Mycoplasma genitalium 482 genes comprising 582,970 base pairs 382 genes Single Cell Minimal Genome 1.8 Mbp Huge Financial Investments Bio-Energy and Drug Production Patent Application US 2007/0122826 and WO/2007/047148 BIODESIGN INDIA 1.0; October 8, 2010 Story of Cynthia/Synthia • http://www.youtube.com/watch?v=cXQhJPdlE lY Other Important Areas • Biofuels • Marine Biology -Natural Products -Biomimicking -Evolutionary Aspects Patterns Clean Technologies Other Areas • Creating genes from Junk DNA • Clipperton Project • Parsi Genome Project Synthetic Biology and Art • • • • • • • • • • BioART Synthetic Aesthetics Univ Edinburgh and Stanford University Art and Design- Science by Design Smell of earth after rain Srishsti Media Arts NCBS Algae tasting like beef Pattern studies and graphical designing Cheese smell Drug Discovery • Biofactories Artemisinin Case (Wormwood Tree) • • • • • • • Call for International Justice Artemisinic acid Artemisia annua Jay Keasling UC Berkley Commercialization Issues Dependence on developed countries Generic Drugs BIODESIGN INDIA 1.0; October 8, 2010 Open Access • • • • • Tools the analytical methods, design software, data will be available to the NON-profit research community • To Companies (that are members of the Center’s industrial consortium) Softwares available • Bio SPICE(Biological Simulation Program for Intra- and Inter-Cellular Evaluation), • a framework and software toolset for modeling & simulation of spatio-temporal processes in living cells • tools for the comparison of genome structure (operon, regulon, etc.) across sequenced microbes • Systems Biology Markup Language (SBML), a computer-readable format for representing models of biological processes. Drew Endy • Chassis Engineering • Interaction between Chassis and System • engineering of biological systems with predictable behavior – Biggest Challenge • Design of standard interface between biological systems and host cell (chassis) Minimal Genome • Chemical Self Assembly • reconstitution of DNA, RNA and protein syntheses from pure components • self-assembly occurs in a definite sequence and is generally energetically favored, obviating the need for enzymes and an energy source. Assembling some type of cell (i.e. a selfreplicating, membrane-encapsulated collection of biomolecules) • Core is cellular replication machinery • Forster and Church • initially define the components sufficient for each subsystem, • allow detailed kinetic analyses • lead to improved in vitro methods for synthesis of biopolymers, therapeutics and biosensors. • Completion would yield a functionally and structurally understood self-replicating biosystem • 113 kbp • 151 genes http://www.nature.com/msb/journal/v2/n1/fig_tab/msb4100090_F1.html Issues • Do I Understand What I Can Create? Biosafety Issues in Synthetic Biology • IPRs • Socio-ethical • Dual Use • Use- Misuse • Bioterrorism • Biosafety • Risk/impact Assessment • Should we learn from GM crops Facts and Forward looking • • • • • • • • Current Market $600 M May rise to $3.5 B Chemical Industry 1.8T (1/5th) Public Awareness 9 to 26% Security Concerns 27% Moral Concerns 25% Health Consequence (-ve) 25% Damage to Environment (13%) Source: www.synbioproject.org The Pros and Cons BIODESIGN INDIA 1.0; October 8, 2010