Bart De Moor - Van systeembiologie naar synthetische biologie

Van systeembiologie naar
synthetische biologie
Bart De Moor
ESAT-SCD
Katholieke Universiteit Leuven
A: Kasteelpark Arenberg 10, B-3001 Leuven
Belgium
T: +32(0)475 2 8 7052
W: www.esat.kuleuven.be/~demoor
E: [email protected]
Inhoud
- ICT: Van analyse naar design
- Bio(techno)logie: Van analyse naar inzicht
- Verdrinken in een tsunami van data
- Van systeembiologie naar synthetische biologie
- Maatschappelijke trends en opportuniteiten
2
1880: Maxwell’s laws (electro-magnetism)
1905: Quanta: Planck and Einstein
1910: Atom model Bohr
1930: Quantummechanics of Heisenberg, Schrödinger,…
1940: Computer (principle) of Turing and von Neumann
1948: Information theory of Shannon
1950: Transistor of Shockley, Bardeen,…
1960: First ‘mainframes’
1963: Moore’s law
1980: ‘A PC at every desk’ (Bill Gates)
1985: Software and databases
1990: Internet and World Wide Web
1995: Smartphones, tablets
2000: Social media
3
De wet van Gordon Moore
‘Understand’ ?
Operations/second
6 10 9
5 10 9
LUI
4 10 9
3D games
3 10
9
2 10 9
1 10 9
Audio
Bookkeeping
0
1975
1980
1985
1990
Video
1995
Year
2000
2005
2010
4
Computing power
Moore’s Law
Computing power doubles every 18 months
5
Connectivity
We are always
CONNECTED
and FAST!
6
Inhoud
- ICT: Van analyse naar design
- Bio(techno)logie: Van analyse naar inzicht
- Verdrinken in een tsunami van data
- Van systeembiologie naar synthetische biologie
- Maatschappelijke trends en opportuniteiten
7
1865: Mendel: Laws of inheritance from statistical inference
1944: Avery/MacLeod/McCarty: DNA = heriditary material
1953: Watson/Crick: DNA double helix
1965: Restriction enzymes: DNA ‘scissors’
1966: Nirenberg/Khorana/Holley: Determine genetic code
1972: Cohen/Boyer: Recombinant DNA, gene transfer in bacteria
1977: Sanger/Maxam/Gilbert: DNA sequencing methods
1982: Insuline by transgene bacteria
1985: Polymerase Chain Reaction (PCR)
1991: First transgene animal: Herman the bull
1994: GM tomatoes to market
1997: First cloned animal: Dolly
2001: Human Genome Completion announced
June 26, 2000
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Guanine
Adenine
Cytosine
Thimidine
9
Y
C
S
W
F
H
P
R
Q
L
N
I
T in DNA
U in RNA
S
T
K
R
M
V
A
D
G
E
-20 amino acids
-64 codons: Redundancy - robustness
Stop=UAA,UAG,UGA
Start=AUG
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February 16, 2001
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Een genoom voor 1000 dollar ?
•
•
Human genome project
– Initial draft: June 2000
– Final draft: April 2003
– 13 year project
– $300 million value
with 2002 technology
Personal genome
– June 1, 2007
– Genome of James Watson, codiscoverer of DNA double helix,
is sequenced
• $1.000.000
• Two months
•
€1000-genome
– Expected 2012-2020
1,00E+11
1,00E+10
1,00E+09
1,00E+08
1,00E+07
1,00E+06
1,00E+05
1,00E+04
1,00E+03
1,00E+02
1,00E+01
1,00E+00
1,00E-01
1,00E-02
1,00E-03
1,00E-04
1,00E-05
1,00E-06
1,00E-07
Cost per base pair
Genome cost
1990
1995
Year
2000
2002
2005
2007
2010
Cost per base pair
2015
Genome cost
1990
10
3E+10
1995
1
3.000.000.000
2000
0.2
600.000.000
2002
0.09
270.000.000
2005
0.03
90.000.000
2007
0.000333333
1.000.000
2010
3.33333E-06
10000
2015
0.0000001
300
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Group
Species
Genes
Genome
(Mbase)
Phages
Bacteriophage MS2
4
0.003560
Viruses
HIV Type 2
9
0.009671
Bacteria
Haemophilus influenzae (1995)
1760
1.83
Archaea
Methanococcus jannaschii
1735
1.74
Fungi
Saccaromyces cerevisiae (yeast) (1996)
5800
12.1
Protoctista
Oxytricha similis
12000
600
Arthropoda
Drosophila melanogaster (fruit fly) (2000)
12000
165
Nematoda
Caenorhabdiis elegans (Round worm)(1998)
14000
100
Mollusca
Loligo Pealii
35000
2700
Plantae
Arabidopsis thaliana (Mustard cress)(2000)
25000
70-145
Chordata
Homo Sapiens
30000
3000
Estimated 265-350 genes are required for ‘life’.
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Inhoud
- ICT: Van analyse naar design
- Bio(techno)logie: Van analyse naar inzicht
- Verdrinken in een tsunami van data
- Van systeembiologie naar synthetische biologie
- Maatschappelijke trends en opportuniteiten
14
Medical Imaging Research Center
Small animal imaging
micro-MRI
micro-PET
Hospital imaging
CT
MR
KU Leuven Core Facilities
Genomics Core
SyBioMa
Next Gen Sequencing GS FLX
– HiSeq 2000 - PacBio
Mass Spectrometry FT-ICR, LTQ,
MALDI, QTof
ACACATTAAATCTTATATGC
TAAAACTAGGTCTCGTTTTA
GGGATGTTTATAACCATCTT
TGAGATTATTGATGCATGGT
TATTGGTTAGAAAAAATATA
CGCTTGTTTTTCTTTCCTAG
GTTGATTGACTCATACATGT
GTTTCATTGAGGAAGGAAC
TTAACAAAACTGCACTTTTT
TCAACGTCACAGCTACTTTA
AAAGTGATCAAAGTATATCA
AGAAAGCTTAATATAAAGAC
ATTTGTTTCAAGGTTTCGTA
AGTGCACAATATCAAGAAG
ACAAAAATGACTAATTTTGT
TTTCAGGAAGCATATATATT
ACACGAACACAAATCTATTT
TTGTAATCAACACCGACCAT
GGTTCGATTACACACATTAA
ATCTTATATGCTAAAACTAG
GTCTCGTTTTAGGGATGTTT
ATAACCATCTTTGAGATTAT
TGATGCATGGTTATTGGTTA
GAAAAAATATACGCTTGTTT
TTCTTTCCTAGGTTGATTGA
genome
GS-FLX Roche
Applied Science 454
transcriptome proteome
metabolome
interactome
Prometa
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Biomedical data
Technological Revolution
increasing throughput & resolution
multichannel, wireless, mobile & realtime
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index of 20
million
Biomedical
PubMed
records
1 slice
mouse brain
MSI at 10
μm
resolution
81 GigaByte
raw NGS data
of 1 full
genome
sequencing all newborns
by 2020 (125k births /
year)
125 PetaByte / year
1 TeraByte
23 GigaByte
1 small
animal
image
1 CDROM
750
MegaByt
e
1 GigaByte
PACS UZ Leuven
1,6 PetaByte
Genomics core
HiSeq 2000 full
speed exome
sequencing
1 TeraByte /
week
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De kennis neemt snel toe
By 2010, 1/3 of all world data bases will consist of biomedical data
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Methodes om te clusteren
lengte
lang
Kenmerken
Clusters
Gelijkvormigheid
Beslissing
kort
zwart
blond
haarkleur
blauw
oranje
Kleur kleren
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Microarray data: genetic
fingerprints
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spin-off founded by Yves
Moreau & Bart De Moor
building on expertise in
big data & machine
learning
BENCH is used in ca. 50 accredited
genetic labs worldwide
Heverlee + US office
routine diagnostics
tools for non-IT users
first diagnostics grade solution
for Next Generation
Sequencing data based
diagnostics in the world
originating from research in
rare genetic disorders in close
collaboration with Centre
Human Genetics UZ Leuven 22
Inhoud
- ICT: Van analyse naar design
- Bio(techno)logie: Van analyse naar inzicht
- Verdrinken in een tsunami van data
- Van systeembiologie naar synthetische biologie
- Maatschappelijke trends en opportuniteiten
23
From Kepler to Newton
Kepler’s laws:
Law 1: Orbit is ellips with Sun in focus
Law 2: Joing line sweeps out
equal areas in equal time
Law 3:
From conic sections
to centripetal forces
and states
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Systems biology: Chemotaxis
‘high throughput ‘data
genome
transcriptome
proteome
metabolome
interactome
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http://www.igem.org/Main_Page
http://www.kuleuven.be/bioscenter/igem/2013/?go=home_2013
Synthetic Biology
Dr. Coli
The bacterial drug
delivery system
Leuven - BELGIUM
Multidisciplinary team
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Slimme bacterie
7 subsystems
 Global system
 Modeling
Input

Output
Reset
Memory
Filter
Cell Death
InverTimer
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in silico model Dr. Coli
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Dr. Coli aan het werk
Geneesmiddel
Celdoodregulator
Geneesmiddel
Geheugen aan: timer en celdood kunnen
gebruikt worden
Reset
Geheugen
uit
beginsituatie
Timer
Timer
ziekte
genezen
Celdood
ziekte
BioSCENTer - K.U.Leuven
genezen
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Inhoud
- ICT: Van analyse naar design
- Bio(techno)logie: Van analyse naar inzicht
- Verdrinken in een tsunami van data
- Van systeembiologie naar synthetische biologie
- Maatschappelijke trends en opportuniteiten
31
Meer aandacht voor gezondheidszorg
-De kwaliteit verbeteren van de gezondheidszorg
-Individuele dokter ondersteunen
-Aantal medische fouten verminderen
-‘Evidence Based Medicine’
-Informatie-uitwisseling tussen dokters
-‘doctor hopping’ vermijden
-1 medische dossier per patient
-Interoperabiliteit tussen ziekenhuizen – mobiliteit van de patient
-‘Empowerment’ van de patient
-4P: personalized, preventive, predictive, participatory
-Gepersonalizeerde therapien
-Transparantie en consistentie verhogen
- Steeds meer chronische patienten met welvaartziektes (hart, diabetes, kanker,…)
-Mobiliteit van de patienten verhoogt steeds meer
-Kosteneffectiviteit van het gezondheidszorgsysteem
-Verouderende bevolking
-EU 2050: 65+  +70%; 80+  +180%
-Vl. 2012: 60+  25 % of Vl.
-Overconsumptie tegengaan
-Detecteer abnormaliteiten in diagnoses, therapieen, voorschrijfgedrag,
-Zorgprogramma’s
-Werken in een tsunami van data
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Demography
1 in 4 Belgians will be over 65 by
2030
 rising health care costs!
Belgian population
[mio]
10
8
6
65+
4
15-64 yrs
2
0
2005
2030
2050
source: Itinera
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Patients make own health care choices
Customization
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Obama
But in order to lead in the global economy and to ensure that our businesses can grow and innovate, and our families
can thrive, we're also going to have to address the shortcomings of our health care system.
The Recovery Act will support the long overdue step of computerizing America's medical records, to reduce the
duplication, waste and errors that cost billions of dollars and thousands of lives. But it's important to note, these
records also hold the potential of offering patients the chance to be more active participants in the prevention and
treatment of their diseases. We must maintain patient control over these records and respect their privacy. At the
same time, we have the opportunity to offer billions and billions of anonymous data points to medical researchers
who may find in this information evidence that can help us better understand disease.
History also teaches us the greatest advances in medicine have come from scientific breakthroughs, whether the
discovery of antibiotics, or improved public health practices, vaccines for smallpox and polio and many other infectious
diseases, antiretroviral drugs that can return AIDS patients to productive lives,
pills that can control certain types of blood cancers, so many others.
Because of recent progress –- not just in biology, genetics and medicine, but also in physics, chemistry, computer
science, and engineering –- we have the potential to make enormous progress against diseases in the coming
decades. And that's why my administration is committed to increasing funding for the National Institutes of Health,
including $6 billion to support cancer research -- part of a sustained, multi-year plan to double cancer research in our
country. (Applause.)
http://www.whitehouse.gov/blog/09/04/27/The-Necessity-of-Science/
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