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Outline Outline What is synthetic biology? y gy How does - - PowerPoint PPT Presentation

Dec 20, 2023 223 likes •647 views

S YNTHETIC B IOLOGY AND D ATA D RIVEN S YNTHETIC D ATA -D RIVEN S YNTHETIC B IOLOGY FOR P ERSONALIZED M EDICINE AND C LEAN E NERGY E NERGY Russell Hanson OSCON D t OSCON Data July 25-27, 2011 J l 25 27 2011 Portland, OR Russell Hanson Russell

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SLIDE 1

SYNTHETIC BIOLOGY AND DATA DRIVEN SYNTHETIC DATA-DRIVEN SYNTHETIC BIOLOGY FOR PERSONALIZED MEDICINE AND CLEAN ENERGY ENERGY

Russell Hanson OSCON D t J l 25 27 2011 OSCON Data July 25-27, 2011 Portland, OR

Russell Hanson Russell Hanson Dec 27, 2004

TheCureIsNow.org

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SLIDE 2

Outline 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

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SLIDE 3

Outline, cont.

  • IP Issues in personalized medicine

IP Issues in personalized medicine

  • Pink Army and co-op, open-source biopharma
  • Non-profit clinical research organizations
  • Non profit clinical research organizations

(CRO’s)

  • Disease-management companies, broken

Disease management companies, broken business model

  • Big Data in electronic medical records,

Big Data in electronic medical records, personal genomics, biostatistics, hospitals, community health centers

OSCON Data – Portland, OR

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SLIDE 4

OSCON Data: This may not be a talk about a social web app and the pp database technologies used for that app, but truly, what would a social web, pp, y, ,

  • etc. app be without the life or biology
  • n that social graph

g p

OSCON Data – Portland, OR

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SLIDE 5

What is life? What is artificial life?

And, incidentally, what is consciousness?

Bernard Baars (1988) Igor Aleksander (1995) Bernard Baars (1988)

  • Definition and context setting
  • Adaptation and learning
  • Editing
  • Flagging and debugging

Igor Aleksander (1995)

  • Brain as state machine
  • Inner neuron partitioning
  • Conscious and unconscious states
  • Perceptual learning and memory
  • Flagging and debugging
  • Recruiting and control
  • Decision-making (executive function)
  • Analogy forming-function
  • Metacognitive and self monitoring
  • Perceptual learning and memory
  • Prediction
  • Self-Awareness
  • Representation and meaning
  • Learning utterances
  • Metacognitive and self-monitoring

function

  • Autoprogramming and self-maintenance

function

  • Definitional and context setting
  • Learning utterances
  • Learning language
  • Will
  • Instinct
  • Emotion

OSCON Data – Portland, OR

  • Definitional and context-setting

function

  • Emotion

from “When The Turing Test Is Not Enough,” by George Dvorsky

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SLIDE 6

We are open source We are open source Life is open source Life is open source We should have excellent tools We should have excellent tools to manage our source (code)

OSCON Data – Portland, OR

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SLIDE 7

OpenWetWare.org

OSCON Data – Portland, OR

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SLIDE 8

BioBricks Foundation

OSCON Data – Portland, OR

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SLIDE 9

iGEM

OSCON Data – Portland OR

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SLIDE 10

NextGen sequencing

OSCON Data – Portland, OR

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SLIDE 11

SNP Chips

OSCON Data – Portland, OR

Affymetrix 500K probe chip ~ $450USD

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SLIDE 12

Single nucleotide polymorphism (SNP) and gene expression arrays

C b fil

  • Copy number profile
  • Gene expression/over expression levels in

a tissue

  • Major copy proportion

j py p p

  • Machine learning on SNPs, SVM, Bayesian

networks, Markov chains networks, Markov chains

  • Biomarker identification, verification, and

development Biomarker for autism “lack

  • development. Biomarker for autism, lack
  • f empathy”

OSCON Data – Portland, OR

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SLIDE 13

Where are we? Where are we?

  • How much do we know about cellular

l ti processes, regulation, oncogenes, protein-protein interactions, microbiome i t ti ? interactions?

  • 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

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SLIDE 14

How to Access the Human Genome (and other sequenced genomes) seque ced ge o es)

  • ftp://ftp.ncbi.nih.gov

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

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SLIDE 15

“The second wave of synthetic biology: from modules to systems” biology: from modules to systems

“The second wave of synthetic biology: from y gy modules to systems,” Purnick PEM, Weiss R, Nature Reviews Molecular Cell Biology, Vol 10 Iss 6 P410-422 Jun 2009

OSCON Data – Portland, OR

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SLIDE 16

Using increasing abstraction, performance characteristics, datasheets -- like integrated circuits (IC’s)

OSCON Data – Portland, OR

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SLIDE 17

Graphical layout, design and ‘programming’ CellDesigner programming , CellDesigner

tutorial at: http://celldesigner.org/~funa/CellDesignerTutorial2007.pdf

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SLIDE 18

Graphical layout, design and ‘programming’ CellDesigner 2 programming , CellDesigner 2

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SLIDE 19

Nanobots to treat NK leukemia cells

DNA scaffolds and cell-surface receptors Software, etc. for DNA

  • rigami, scaffold design

OSCON Data – Portland OR

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SLIDE 20

23andMe, NextGen sequencing and SynBio get together SynBio get together

  • 23andMe version 3 uses

Illumina HumanOmniExpress BeadChip SNP chips BeadChip SNP chips ($250/sample)

  • Genome Wide Association
  • Genome Wide Association

Studies

  • --> At $250/sample,

genomic personalization is

OSCON DATA – Portland, OR

genomic personalization is very realizable

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SLIDE 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 ClothoCAD

  • RepRap – exponentially

scalable matter compiler /extruding 3D printer / g p

OSCON Data – Portland, OR

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SLIDE 22
  • Movie at:

http://www.molecularmovies.com/movi p // / es/berry_apoptosis.html

OSCON Data – Portland, OR

Apoptosis Maya Animation by Drew Berry

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SLIDE 23

Biological “simulators” Biological simulators

  • NAMD – and other molecular dynamics, etc.

NAMD and other molecular dynamics, etc.

  • Mixed Quantum Mechanics/Molecular

Mechanics (QM/MM/ ) Mechanics (QM/MM/…)

  • Biological pathway/chemical reaction

simulators/optimizers simulators/optimizers

  • Many projects on gene network analysis,

h i i l i stochastic simulation, etc.

OSCON Data – Portland, OR

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SLIDE 24

Design of bio/chemical devices from (1) fi t i i l d f ti l (1) first principles and functional abstractions and (2) from data

Data Bio/chem/phys first principles

OSCON DATA – Portland, OR

and functional abstractions

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SLIDE 25

How and where these data are used or made usable used, or made usable

  • Randomized clinical trials
  • Biomarker development, genomic tests

in CLIA certified labs in CLIA certified labs

  • Licensing to other companies for

marketing and development marketing and development

OSCON Data – Portland, OR

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SLIDE 26

Tools that are used to analyze these data these data

  • R (!), BioConductor

R (!), BioConductor

  • Biostatistics, Matlab

Python

  • Python
  • Chi-square tests,

permutation tests, Monte Carlo resampling

  • Parametric statistics, nonparametric

Parametric statistics, nonparametric statistics, generative statistics

  • Statistical learning theory online learning
  • Statistical learning theory, online learning

OSCON Data – Portland, OR

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SLIDE 27

Approval of processes for cellular therapies/treatments

FDA l f t f

  • FDA approval for process, not for

drug/biologic/device

“…progress on the development of a new experimental MCL treatment called immunotherapy, in which a patient’s own immune cells are collected from the bloodstream before ASCT, treated in the laboratory to have antitumor activity, and reintroduced into the body after ASCT. The goal of this immunotherapy is to reduce the likelihood of relapse after transplantation. A major challenge of immunotherapy is getting the transferred immune cells to persist in the body ft th t f I li i l t di D J d hi ll f d after the transfer. In preclinical studies, Dr. Jensen and his colleagues found that using a certain subset of immune cells called central memory T-cells in- creased the likelihood that the transferred T-cells will persist.”

OSCON Data – Portland, OR

Report from the Lymphoma Research Foundation, Spring 2010, Volume 8, Number 1

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SLIDE 28

Pink Army – a bi h biopharma co-op

  • You own your own cells, therapies based off your

You own your own cells, therapies based off your

  • wn cells should be yours in the co-op.
  • If a biopharma company cures your disease, they

If a biopharma company cures your disease, they lose a customer, who is cured. 2 weeks and 2 weeks and $1000 in lab resources

OSCON Data – Portland OR

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SLIDE 29

Cancer 5-year survival rates, US

OSCON Data – Portland, OR

Division of Cancer Control and Population Sciences, 2008

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SLIDE 30

Non-profit clinical research ( ’ )

  • rganizations (CRO’s)
  • Randomized trials
  • A melanoma trial with 1 000 patients
  • A melanoma trial with 1,000 patients

costs $60M in CRO expenses

  • A 10 000 patient chronic obstructive
  • A 10,000 patient chronic obstructive

pulmonary disease (COPD) costs $240- $250M in CRO expenses $250M in CRO expenses

OSCON Data – Portland, OR

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SLIDE 31

More medical foci of SynBio y

  • Oncolytic viruses

y

  • RNAi for HER2 in breast cancer (also an

iGEM team project) iGEM team project)

  • Designed, logic, and ‘programmed’

Not comp tational de ices b t se logic

  • Not computational devices but use logic

and/or procedures

OSCON Data – Portland OR

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SLIDE 32

Using data to engineer therapies

  • r cures for genetic diseases
  • r cures for genetic diseases

RNA AND AND RNA AND AND RNA AND AND RNA AND AND RNA IF IF ( ) ( ) THEN THEN RELEASE RELEASE PROTEIN PROTEIN INITIATING INITIATING APOPTOSIS APOPTOSIS IN IN THE THE TUMOR TUMOR CELL CELL

OSCON Data – Portland OR

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SLIDE 33

More biological nanobots

T t h d l b t d f bi l i l i

  • Tetrahedral robots, made from biological or organic

substrate: 12Tet Tetrahedral Rover Robot http://www.youtube.com/watch?v= txZMLS7YD6Q http://www.youtube.com/watch?v txZMLS7YD6Q

OSCON Data – Portland, OR

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SLIDE 34

More biological nanobots, 2

DNA O i i DNA Origami

OSCON Data – Portland, OR

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SLIDE 35

Energy biofules and bioreactors Energy, biofules, and bioreactors

‘The oil multinational, despised by green activists for its support of , p y g f pp f scientists skeptical of climate change, plans to invest $600 million (£370 million) in a joint venture with Mr Venter’s company, Synthetic Genomics. The thinking is that algae is a more efficient source of fuel than conventional biofuels, such as ethanol made from corn or sugar cane and biodiesel made from wheat or palm oil. Algae can be processed into fuels similar to petrol and diesel — and it consumes carbon dioxide as it grows. A di E h i ld f bi f l f l i 2 000 ll According to Exxon, the yield of biofuel from algae is 2,000 gallons per acre, more than three times that of biodiesel from palm oil and eight times the ethanol yield from corn. It is also believed to have the edge over other biofuels because of its suitability for use as a jet fuel “The real challenge to biofuels because of its suitability for use as a jet fuel. The real challenge to creating a viable, next-generation biofuel is the ability to produce it in large volumes,” Mr Venter said.’ via http://www.timesonline.co.uk/tol/news/environment/article6710846.ece

OSCON Data – Portland OR

via http://www.timesonline.co.uk/tol/news/environment/article6710846.ece

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SLIDE 36

Biological light sources

E.glowli: a bioluminescent future

U Cambridge, iGEM 2010 team

OSCON Data – Portland, OR

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SLIDE 37

Biological memory

CUHK, iGEM 2010 team

OSCON Data – Portland OR

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OSCON Data – Portland, OR

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SLIDE 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

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SLIDE 40

And so forth… and biology

  • PolySilicon and biology
  • SynBio in chemicals industry – cleaning
  • SynBio in chemicals industry – cleaning,

refinement, scalability, sensors, etc.

OSCON Data – Portland, OR

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SLIDE 41

Conclusions

  • Wide ranging implications to existing problems in

health, engineering, energy, manufacture P ti l l f h h lth i h

  • Particularly for human healthcare, genomic research
  • n diseases, data-aided design and testing
  • New manufacture processes for new biologically-

New manufacture processes for new biologically designed constructs

http://www.linkedin.com/in/russellhanson http://twitter.com/russell_hanson http://www russellhanson com/

OSCON Data – Portland OR

http://www.russellhanson.com/