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Synthetic Biology and Data-Driven Synthetic Biology for Personalized Medicine and Clean Energy at O\'Reilly\'s OSCON Data in Portland, OR
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Synthetic Biology and Data-Driven Synthetic Biology for Personalized Medicine and Clean Energy at O\'Reilly\'s OSCON Data in Portland, OR


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A talk I gave at OSCON Data 2011 on how personalized medicine, data analysis, and open source synthetic biology can work together.

A talk I gave at OSCON Data 2011 on how personalized medicine, data analysis, and open source synthetic biology can work together.

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  • 2. Outline• What is synthetic biology? y gy• How does synthetic biology relate to genomic science/personalized medicine• “Open source” tools in science and bioengineering/synbio• Bio-Computer aided design (AutoCAD, etc.)• Mesoscopic Physics p y• Diff Eqs and parameter optimizations OSCON Data – Portland, OR
  • 3. Outline, cont.• IP Issues in personalized medicine• Pink Army and co-op, open-source biopharma• Non-profit clinical research organizations Non profit (CRO’s)• Disease-management companies, broken Disease management business model• Big Data in electronic medical records, personal genomics, biostatistics, hospitals, community health centers OSCON Data – Portland, OR
  • 4. OSCON Data: This may not be a talkabout a social web app and the ppdatabase technologies used for thatapp, but truly, what would a social web, pp, y, ,etc. app be without the life or biologyon that social graph g p OSCON Data – Portland, OR
  • 5. What is life? What is artificial life? And, incidentally, what is consciousness? Igor Aleksander (1995) Bernard Baars (1988) • Brain as state machine • Definition and context setting • Inner neuron partitioning • Adaptation and learning • Conscious and unconscious states • Editing • Perceptual learning and memory • Flagging and debugging • Prediction • Recruiting and control • Self-Awareness • Decision-making (executive function) • Representation and meaning • Analogy forming-function • Learning utterances • Metacognitive and self monitoring self-monitoring • Learning language function • Will • Autoprogramming and self-maintenance • Instinct function • Emotion • Definitional and context-setting context setting function OSCON Data – Portland, ORfrom “When The Turing Test Is Not Enough,” by George Dvorsky
  • 6. We are open source Life is open sourceWe should have excellent toolsto manage our source (code) OSCON Data – Portland, OR
  • 7. OSCON Data – Portland, OR
  • 8. BioBricks Foundation OSCON Data – Portland, OR
  • 9. iGEM OSCON Data – Portland OR
  • 10. NextGen sequencing OSCON Data – Portland, OR
  • 11. SNP ChipsAffymetrix 500K probe chip ~$450USD OSCON Data – Portland, OR
  • 12. Single nucleotide polymorphism(SNP) and gene expression arrays•CCopy number profile b fil• Gene expression/over expression levels in a tissue• Major copy proportion j py p p• Machine learning on SNPs, SVM, Bayesian networks, Markov chains• Biomarker identification, verification, and development. development Biomarker for autism “lack autism, lack of empathy” OSCON Data – Portland, OR
  • 13. Where are we?• How much do we know about cellular processes, regulation, oncogenes, l ti protein-protein interactions, microbiome interactions? i t ti ?• How much do we know about brain structure-function relationships, gene activation in neurons, memory, eletrophysiology, neuronal cognition, brainmaps from C. elegans, to Mus musculus, to Homo sapiens? OSCON Data – Portland, OR
  • 14. How to Access the Human Genome (and other seque ced genomes) sequenced ge o es)• hs_phs0.fna.gz Survey sequence (appr hs_phs1.fna.gz Unordered contigs (ea hs_phs2.fna.gz Ordered contigs (each hs_phs3.fna.gz Finished sequence 21C3 – Berlin
  • 15. “The second wave of synthetic biology: from modules to systems systems”“The second wave of synthetic biology: from y gymodules to systems,” Purnick PEM, Weiss R,Nature Reviews Molecular Cell Biology, Vol 10 OSCON Data – Portland, ORIss 6 P410-422 Jun 2009
  • 16. Using increasing abstraction, performance characteristics, datasheets -- like integrated circuits (IC’s) OSCON Data – Portland, OR
  • 17. Graphical layout, design and ‘programming’, CellDesigner programmingtutorial at:
  • 18. Graphical layout, design and‘programming’, CellDesigner 2 programming
  • 19. Nanobots to treat NK leukemia cellsDNA scaffolds andcell-surface receptorsSoftware, etc. for DNAorigami, scaffold design OSCON Data – Portland OR
  • 20. 23andMe, NextGen sequencing and SynBio get together• 23andMe version 3 uses Illumina HumanOmniExpress BeadChip SNP chips ($250/sample)• Genome Wide Association Studies• --> At $250/sample, genomic personalization is very realizable OSCON DATA – Portland, OR
  • 21. More new CAD/BioCAD software tools• ‘Matter compiler’• Thingiverse, cheap 3d printers, laser g , p p , cutters, Shapeways, personal fab technology, makerbot, etc. gy, ,• AutoDesk, EugeneCAD,ClothoCAD• RepRap – exponentiallyscalable matter compiler//extruding 3D p g printer OSCON Data – Portland, OR
  • 22. • Movie at: p // / es/berry_apoptosis.htmlApoptosis Maya Animation by Drew Berry OSCON Data – Portland, OR
  • 23. Biological “simulators” simulators• NAMD – and other molecular dynamics, etc.• Mixed Quantum Mechanics/Molecular Mechanics (QM/MM/…) (QM/MM/ )• Biological pathway/chemical reaction simulators/optimizers• Many projects on gene network analysis, stochastic simulation, etc. h i i l i OSCON Data – Portland, OR
  • 24. Design of bio/chemical devices from(1) first principles and functional fi t i i l df ti labstractions and (2) from data DataBio/chem/phys first principlesand functional abstractions OSCON DATA – Portland, OR
  • 25. How and where these data are used, used or made usable• Randomized clinical trials• Biomarker development, genomic tests in CLIA certified labs• Licensing to other companies for marketing and development OSCON Data – Portland, OR
  • 26. Tools that are used to analyzethese data• R (!), BioConductor• Biostatistics, Matlab• Python• Chi-square tests,permutation tests, Monte Carlo resampling• Parametric statistics, nonparametric statistics, generative statistics• Statistical learning theory, online learning theory OSCON Data – Portland, OR
  • 27. Approval of processes for cellular therapies/treatments • FDA approval for process, not f lf t for drug/biologic/device“…progress on the development of a new experimental MCL treatment calledimmunotherapy, in which a patient’s own immune cells are collected from thebloodstream before ASCT, treated in the laboratory to have antitumor activity,and reintroduced into the body after ASCT. The goal of this immunotherapy isto reduce the likelihood of relapse after transplantation. A major challenge ofimmunotherapy is getting the transferred immune cells to persist in the bodyafter the transfer. In preclinical studies, Dr. Jensen and his colleagues found ft th t f I li i l t di D J d hi ll f dthat using a certain subset of immune cells called central memory T-cells in-creased the likelihood that the transferred T-cells will persist.”Report from the Lymphoma Research Foundation, Spring 2010, Volume 8,Number 1 OSCON Data – Portland, OR
  • 28. Pink Army – a biopharma co-op bi h• You own your own cells, therapies based off your own cells should be yours in the co-op.• If a biopharma company cures your disease, they lose a customer, who is cured. 2 weeks and $1000 in lab resources OSCON Data – Portland OR
  • 29. Cancer 5-year survival rates, US OSCON Data – Portland, ORDivision of Cancer Control and Population Sciences, 2008
  • 30. Non-profit clinical research organizations ( (CRO’s) ’ )• Randomized trials• A melanoma trial with 1,000 patients 1 000 costs $60M in CRO expenses• A 10,000 patient chronic obstructive 10 000 pulmonary disease (COPD) costs $240- $250M in CRO expenses OSCON Data – Portland, OR
  • 31. More medical foci of SynBio y• Oncolytic viruses y• RNAi for HER2 in breast cancer (also an iGEM team project)• Designed, logic, and ‘programmed’• Not comp tational devices b t use logic computational de ices but se and/or procedures OSCON Data – Portland OR
  • 32. Using data to engineer therapies or cures for genetic diseasesIF ( RNA AND RNA AND RNA AND RNA AND RNA )THEN RELEASE PROTEIN INITIATING APOPTOSIS IN THE TUMOR CELL OSCON Data – Portland OR
  • 33. More biological nanobots• T t h d l robots, made from biological or organic Tetrahedral b t d f bi l i l i substrate: 12Tet Tetrahedral Rover Robot txZMLS7YD6Q OSCON Data – Portland, OR
  • 34. More biological nanobots, 2DNA O i Origami i OSCON Data – Portland, OR
  • 35. Energy, biofulesEnergy biofules, and bioreactors ‘The oil multinational, despised by green activists for its support of , p yg f pp fscientists skeptical of climate change, plans to invest $600 million (£370million) in a joint venture with Mr Venter’s company, Synthetic Genomics. Thethinking is that algae is a more efficient source of fuel than conventionalbiofuels, such as ethanol made from corn or sugar cane and biodiesel madefrom wheat or palm oil. Algae can be processed into fuels similar to petroland diesel — and it consumes carbon dioxide as it grows. According to Exxon, the yield of biofuel from algae is 2,000 gallons per A di E h i ld f bi f l f l i 2 000 llacre, more than three times that of biodiesel from palm oil and eight times theethanol yield from corn. It is also believed to have the edge over otherbiofuels because of its suitability for use as a jet fuel. “The real challenge to fuel Thecreating a viable, next-generation biofuel is the ability to produce it in largevolumes,” Mr Venter said.’via OSCON Data – Portland OR
  • 36. Biological light sourcesE.glowli: a bioluminescent future U Cambridge, iGEM 2010 team OSCON Data – Portland, OR
  • 37. Biological memory CUHK, iGEM 2010 team OSCON Data – Portland OR
  • 38. OSCON Data – Portland, OR
  • 39. Microbiome Engineering• Use the microbiome to produce therapies for existing diseases in controlled, continuous ways: insulin for diabetics, interleukin 10 for Crohn’s disease, etc.• Highly competitive environment: microbe needs orthogonal edge to survive g g OSCON Data – Portland, OR
  • 40. And so forth… and biology• PolySilicon and biology• SynBio in chemicals industry – cleaning cleaning, refinement, scalability, sensors, etc. OSCON Data – Portland, OR
  • 41. Conclusions• Wide ranging implications to existing problems in health, engineering, energy, manufacture• P ti l l for human healthcare, genomic research Particularly f h h lth i h on diseases, data-aided design and testing• New manufacture processes for new biologically- biologically designed constructs russellhanson com/ OSCON Data – Portland OR