Synthetic Biology Genetic Engineering

What is it?

Genetic Engineering + Engineering

Synthetic Biology The construction of completely novel biological entities, and the re-design of already existing ones.

Where does it fit?

Systems Biology Merger of Systems and Control Theory with Molecular and Cell Biology. Aims to explain emergent properties of complex biological systems arising from interactions among their parts. Is about quantitative, predictive and dynamic biology.

SynBio and SysBio For systems biology important to discover design principles common in physics and engineering, but so far elusive in biology. If design principles discovered will be able to design biological systems having desired properties – synthetic biology

Technology Impact

Basic Tools from GE Recombinant DNA PCR Automated Sequencing

Basic Tools - New Automatic Construction Abstraction Standardization Reliable Behavior

ComputingGenetics Digital CodeA, T, G, C Open StandardCodons Modular CodeGenes Error ProtectionDNA Repair Data CompressionOverlapping ORFs Redundant BackupDouble Helix, Copy Number Self-diagnosticsApoptosis Operating SystemRibosomes Genetics as Computing

Scientific MethodEngineering Design Process State QuestionDefine Problem Gather Background Information Formulate Hypothesis, Identify Variables Specify Requirements, Design Criteria Design Experiment, Establish Procedures Prepare Preliminary Designs, Choose Best One Perform ExperimentBuild Prototype Analyze Results and Draw Conclusions Verify, Test and Redesign as Necessary Present Results Science versus Engineering

“ What I cannot create, I do not understand.” - Richard Feynman

Synthetic Biology Space

SynBio Subfields DNA-based biological circuits Minimal genome/minimal life Protocells DNA chemical synthesis machines Orthogonal biological systems

DNA-based biological circuits

Computer Engineering Inspired Hierarchy

Electric Circuit

Biological NOT gate

Biological NAND gate

BioBrick Parts DNA sequences of defined structure and function that share a common interface and designed to be incorporated into living cells to construct new biological systems

Parts

Inverter Device

Inverter with PoPs

Biobrick Hierarchy

Standardization

Molecular Computing

Minimal genome/minimal life Protocells and

Orthogonal biological systems (Xenobiology - XNA)

Xeno nucleotides

Playing God?

SynBio Applications

Two Novel Entities

Societal aspects of SynBio

“Half-pipe of Doom” PromisePeril Safety and Security of Biotechnology

Ethical Assessment Principles Public Beneficence Responsible Stewardship Intellectual Freedom and Responsibility Democratic Deliberation Justice and Fairness

Social and Ethical Challenges of SynBio Biosafety Environmental release Bioterrorism Scientific and economic monopolies Exacerbating global inequalities in trade Creating artificial life

Current Status of SynBio

Five Hard Truths Many Parts Undefined Circuitry Unpredictable Complexity Unwieldy Many Parts Incompatible Variability Crashes System Five Hard Truths for Synthetic Biology - Nature Jan 2010

SynBio – June 2011 Synthesize an enzyme but not design a protein Synthesize a chromosome but not predictably engineer a circuit Unknown how to engineer on a whole genome basis Unknown how to interface with inorganic material Synthetic Biology 5.0: The Fifth International Meeting on Synthetic Biology,

SynBio Grand Challenge Areas Building Block Biology Characterization Systems Engineering

Building Block Challenges Synthesize the full genome of a bacterium Design and manufacture a minimal cell Design bacteria that hunt and kill tumors Enhance the photosynthesis process in plants Expand model organism culturing capability from E. coli and yeast to the vast number of microbes

Bio Characterization Challenges Understand the key interactions of band gap material in a cell Understand the multigenic epistasis of thousands of genes in heterologous systems Understand contact from a cellular basis Figure out how to create programmatic control of complex development steps (for example, body plan) Define how many changes are necessary to create a new species

Systems engineering challenges Define designs and specifications that can be predictably and reliably verified and constructed Improve challenges in the synthesis, design, analysis of existing systems Engineer for the open systems of the real world, beyond closed-environment bioreactors Improve tools for computer-based circuit, genome, and chromosome design

Systems engineering challenges 2 Develop theoretical frameworks to scale synbio to bigger questions; envision the future beyond putting a lot of small pieces of DNA together more quickly and cheaply Develop effective means to design, generate, and test recombinant organisms in the environment (for example, injestable bacteria in humans like an organism that cures cancer or probiotic bacteria for Crohn’s disease)

Gartner Hype Cycle SynBio

What if we figure it all out?