MIT Molecular Machines (Jacobson) Group Building a FAB for Synthetic Biology

Synthetic Biology to Program Cells to Become Factories to Make… Devices, Sensors, Pharmaceuticals, Renewable Chemicals & Fuels and Food Using Synthetic Genes… Tape Programming of the Mark I Computer Ribosome only 10 6 times smaller Like this

Cells as Chemical Factories 1,3 Propanediol modification.html

MB Elowitz MB and S Leibler (2000) A synthetic oscillatory network of transcriptional regulators.Nature.403 : Cells as Computers and Logic Ring Oscillators from Transcriptional-Translational Logic

Jeff Hasty - UCSD Bacterial Ring Oscillators

Silicon From Schematic Design To Fab To Working Chip To Product

The Tyranny of Numbers

DNA Synthesis Chemical Synthesis (Open Loop Protection Group) Biological Synthesis (Error Correcting Polymerase) Error Rate: 1:10 2 Throughput: 300 S per Base Addition Throughput Error Rate Product Differential: ~10 8 template dependant 5'-3' primer extension 5'-3' error-correcting exonuclease 3'-5' proofreading exonuclease Error Rate: 1:10 6 Throughput: 10 mS per Base Addition Beese et al. (1993), Science, 260, sm/xtal/teach/repl/klenow.html

A. Gene pathway sequence. B. Corresponding array of overlapping oligonucleotides C. Error correcting assembly in to low error rate pathways. D. Expression in cells BioFAB - From Bits to Cells A B C D

~ 1M Oligos/Chip Next Generation (Chip Based) DNA Synthesis Chow, Brian Y., Christopher J. Emig, and Joseph M. Jacobson. "Photoelectrochemical synthesis of DNA microarrays." Proceedings of the National Academy of Sciences (2009): Accurate multiplex gene synthesis from programmable DNA microchips Jingdong Tian, Hui Gong, Nijing Sheng, Xiaochuan Zhou, Erdogan Gulari, Xiaolian Gao and George Church Nature 432, (23 December 2004) doi: /nature03151 ~1000x Lower Oligonucleotide Cost

J. Jacobson – MIT CBA – M 10G 1T 100T Base Pairs 100M ~ 200 Mbp ~ 250 Mbp ~ 1.5 Gbp ~ 1.6 Gbp~ 3.2 Gbp Gbp ~ 200 Gbp G Transistors 97 Mbp ~1-13 Mb Scale Factors in DNA Synthesis & Applications Next Generation (Chip Based) DNA Synthesis 12.2 Mbp

Bio Parts for Synthetic Biology parts.igem.org

Digital Biology Creating a Fab for Biology Synthetic Biology Apps

The Genetic Code Life’s Operating System Genetically Recoded Organisms

The Genetic Code Currently Powering 8.7 Million Species on Earth Organisms Currently Running the Standard Genetic Code Organisms Running a Different Genetic Code hydrophobic hydrophilic Acetohalobium arabaticum Candida albicans Pterobranchia mitochondrial code

18 October 2013 Conferring New Function Phage Resistance

Years 1 2 Global Cumulative Unit Shipments (Millions) Cumulative Units with Android & iOS Installed Cumulative Units with GRO OS Installed Hours Android / iOS Roll Out VS. GRO - OS