@krknrm
2003 2008 2010 2014 2016 2018
BSc Biochemistry
UAM
Madrid, Spain
MSc Mol Bio
UAM
Madrid, Spain
FPU Fellow
CNIO/UAM
Madrid, Spain
Research
Fellow
WCMC
NYC, US
Wushu Martial Arts
3rd at Spanish Nationals
(Traditional Styles)
Running
PB Marathon: 3h 47m
EMBO-LT
& MSCA
Fellow
UoE
Edinburgh, UK
PhD!
Environmental Volunteer
SEO Birdlife
15M Economy
Working Group
Technician at
Ciencia En El Parlamento
(Cybersecurity, Open Data
and E-Democracy)
ECUSA-NY
Career Dev Director
Fostering Grads
ECUSA Mentor
Excellence in
Academic Performance
(CAM)
Miguel Foronda
Keywords: Cancer research, genome editing, aging, stem
cells, regeneration, telomeres, WNT, colorectal cancer,
epithelial cancer, Cybersecurity, Open Data, E-Democracy
@krknrm
www.linkedin.com/in/miguelforonda/
WHO IS THIS GUY?
Links between Biology & Computation
SPACE + ENERGY = OBSOLESCENCE
Fav Quote: Biology IS the next computation (Unknown source L )
…when this baby runs, it can store up to ONE song or photo (1956 rant)!!
We are constantly miniaturizing our data storage devices (and we need this)…
…yet, this leads to an almost instant obsolescence for everything digital
DNA digital data storage
So, what’s with DNA data storage?
THE REQUIREMENTS OF DNA DATA STORAGE
TTCATG…
0100011…
TTCATG…
0100011…
The requirements of ANY data storage device
Some numbers:
- Each nucleotide = 0.34Å (0.34x10-9 m)
- Each cell = 6 billion nt (6x109) = 1.8 m DNA
- Each human = 3.72x1013 cells
DNA STRUCTURE AND COMPOSITION
What is this thing called DNA? Deoxyribonucleic acid, structure and function
…G A T T A C A…
… G A T T A C A …
… 1 0 0 0 0 1 0 …
A, T = 0
C, G = 1
Shannon information capacity of DNA = 1
(More flexibility in coding)
DNA *IS* A DIGITAL DATA STORING SYSTEM
Depending on the encoding method, we can achieve different capacities
(Shannon information capacity index calculation for DNA)
Erlich Y et al, Science 2017
…G A T T A C A…
… G A T T A C A …
…10 00 11 11 00 01 00…
A = 00
C = 01
G = 10
T = 11
Shannon information capacity of DNA = 2
(Biological constraints à ~1.58)
DNA *IS* A DIGITAL DATA STORING SYSTEM
Depending on the encoding method, we can achieve different capacities
(Shannon information capacity index calculation for DNA # 2)
Erlich Y et al, Science 2017
DNA *IS* A DIGITAL DATA STORING SYSTEM
Nature has its own ways of encoding information in DNA
(nucleotide triplets=aminoacids)
Erlich Y et al, Science 2017
DNA Fountain à Densidad de información: 215 PB/g DNA
DNA *IS* A DIGITAL DATA STORING SYSTEM
DNA Fountain,
or how to store ALL the information in just one minivan
Erlich Y et al, Science 2017
DNA Fountain?
The arrival of a train at La Ciotat, 1896
EXCHANGING INFORMATION USING DNA: HIGH FIDELITY
DNA Fountain, does it work, really?
Spoiler: yes, it does!
Hoshika S et al, Science 2019
Nature 566, 436 (2019)
4 SYNTHETIC BASES TO EXPAND THE CODING POTENTIAL OF DNA
DNA constraints,
Do we have enough with just FOUR letters? Let’s make some more!
Kate Rubins, NASA, 2016
SEQUENCING DNA IS READING IN A FOUR LETTER ALPHABET
Sequencing modalities, speed and precission:
With nanopore technologies, sequencing needs just an USB drive-like device
THE PRICE OF SEQUENCING: PLUMMETTING SINCE 2001
Sequencing DNA,
Can we really afford this? The cost of sequencing, then and now.
Erlich Y et al, Science 2017
Veces que se podría reproducir “Despacito”
1.5x1015*
(* tal vez más)
HOW MANY TIMES CAN WE RETRIEVE DATA FROM THE SAME DNA FILE?
How many times can we reproduce data from DNA?
The “Despacito” Paradigm – we can have as much as we need
1 Ma 12 Ka 5 Ka
PLEISTOCENO H.Neol
HOLOCENO
DNA IS ***VERY*** STABLE
Time Scale of DNA stability
…It really lasts long
DNA IS ***VERY*** STABLE
Yuka mammoth
~28.000 years
Yamagata et al Sci Rep 2019
Time Scale of DNA stability
…It really lasts long
Time Scale of DNA stability
…and some cool stuff that has been successfully sequenced !
A (POTENTIAL) DNA-BASED TIME CAPSULE
Svalbard Global Seed Vault
Arctic World Archive
DNA STORAGE ONLY REQUIRES (SOME) COLD
Arctic World Archive
(PIQL)
GUESS WHOSE INFO STORAGE STRATEGY IS “PICKLED”?
Current strategies to preserve data are “pickled”
i.e., they didn’t use DNA but photographic film L
1970s 1980s 1990s 2000s
THE EVOLUTION OF DATA STORAGE PARALLELS THAT OF CHER’S HAIRSTYLE
You can change your style, but you can’t change your soul
Things become eventually obsolete and useless -but DNA
àAs long as there are human beings, we’ll be able to read DNA data
…ABOUT THIS THING IN YOUR TRUNK??
“Have some pickles innit, mate?”
Organick L et al, Nat Biotechnology 2017
Vs.
RANDOM ACCESS CAN BE EMBEDDED IN THE ENCODING METHOD
…About random access…it’s just proper encoding!
DNA-based
Magnetic-based
2019
Costperbit
???
=$7000
MAKE DNA (GREAT AGAIN)
Eventually, the costs of DNA synthesis
will match or surpass magnetic data recording
CRISPR molecular recording
OR: can we make living recorder organisms using their DNA and CRISPR?
Francis Mojica
THE ORIGINS OF CRISPR ARE IN ALICANTE (NOT A JOKE!)
The discovery of CRISPR and the importance of basic research
PublicationsPerYear
4000
3000
2000
1000
0
2018
2010
2015
2016
2017
2014
2013
2012
2011
2004
2009
2008
2007
2006
2005
CUSTOM (FAST, PRECISE)
GENOME MANIPULATION
CRISPR IS TO GENOME EDITING LIKE QUANTUM IS TO COMPUTING
Some ethics involved here, don’t edit
your babies at home (or your lab)
See Lluis Montoliu for reference @LluisMontoliu
Source: The Doudna Lab (www.doudnalab.org )
CRISPR IS A TWO-STEP BACTERIAL IMMUNITY MECHANISM
How CRISPR was intended to be used in nature?
Source: The Doudna Lab (www.doudnalab.org )
CRISPR IS A TWO-STEP BACTERIAL IMMUNITY MECHANISM
Foronda et al, Unpublished
Tang W et al, Science 2018
GENOME EDITING CAN BE TRACED: A SIMPLE MOLECULAR RECORDER
CRISPR as molecular recorders of different sorts – including from our lab!
Source: The Doudna Lab (www.doudnalab.org )
CRISPR IS THE BLOCKCHAIN OF BACTERIAL IMMUNITY
“Pixets” are sets of pixels encoded in oligonucleotides
Where the 1st 4 nucleotides encode pixet ID,
position within the oligont encodes pixel positions
and triplets encode gray scale
Acquiring pixets along a time frame resolves into a GIF!
Encoded GIF (36x26 pixels)
Human and animal locomotion (Eadweard Muybridge)
Frame 1 Frame 2 Frame 3 Frame 4 Frame 5
RECORDING GIFS IN BACTERIAL POPULATIONS
IMAGEN ORIGINAL RECONSTRUCCIÓN
A PARTIR DE BACTERIAS
Source: Shipman SL et al, Science 2016
Shipman SL et al, Nature 2017
RECORDING GIFS IN BACTERIAL POPULATIONS
Acquiring pixets along a time frame resolves into a GIF!
WARNING: real data J
Molecular machines
Molecular machines for embedded computational functions
DNA ORIGAMI AS A SCAFFOLDING FOR BIOLOGICAL MACHINES
DNA origami: Why fold DNA into specific structures?
Rothemund, Nature 2006
DNA ORIGAMI AS A SCAFFOLDING FOR BIOLOGICAL MACHINES
DNA origami requires a lot of computation (and design!)
Chao et al, Nature Materials 2018
Chatterjee et al, Nature Nanotech, 2017
SINGLE-MOLECULE DNA NAVIGATORS
Example: single-molecule DNA navigators to solve mazes…
DNA ORIGAMI-BASED MAZES – like nodes in a graph
…because each node in the maze can be visualized as a graph
node (decision tree)…
Chao et al, Nature Materials 2018
PARALLEL-DEPTH FIRST SEARCH USING DNA NAVIGATORS
…allowing us to solve the maze by retrieving ALL THE POSSIBLE
SOLUTIONS AT ONCE (how about that, quantum computing?)
SI TE HAS DORMIDO EN LA CHARLA:
1.- El DNA ES un Sistema de almacén digital de datos estable, robusto y
energéticamente eficiente (y caro) (por ahora)
2.- CRISPR sirve como grabadora molecular analógica y digital (además de
muchas otras cosas)
3.- Los DNA navigators son capaces de PDFS, generando materiales
moleculares con funciones computacionales embebidas
DNA ROCKS!
DOW Lab
CEEP Family

Miguel Foronda T3chfest

  • 1.
  • 2.
    2003 2008 20102014 2016 2018 BSc Biochemistry UAM Madrid, Spain MSc Mol Bio UAM Madrid, Spain FPU Fellow CNIO/UAM Madrid, Spain Research Fellow WCMC NYC, US Wushu Martial Arts 3rd at Spanish Nationals (Traditional Styles) Running PB Marathon: 3h 47m EMBO-LT & MSCA Fellow UoE Edinburgh, UK PhD! Environmental Volunteer SEO Birdlife 15M Economy Working Group Technician at Ciencia En El Parlamento (Cybersecurity, Open Data and E-Democracy) ECUSA-NY Career Dev Director Fostering Grads ECUSA Mentor Excellence in Academic Performance (CAM) Miguel Foronda Keywords: Cancer research, genome editing, aging, stem cells, regeneration, telomeres, WNT, colorectal cancer, epithelial cancer, Cybersecurity, Open Data, E-Democracy @krknrm www.linkedin.com/in/miguelforonda/ WHO IS THIS GUY?
  • 3.
    Links between Biology& Computation SPACE + ENERGY = OBSOLESCENCE Fav Quote: Biology IS the next computation (Unknown source L )
  • 4.
    …when this babyruns, it can store up to ONE song or photo (1956 rant)!! We are constantly miniaturizing our data storage devices (and we need this)…
  • 5.
    …yet, this leadsto an almost instant obsolescence for everything digital
  • 6.
    DNA digital datastorage So, what’s with DNA data storage?
  • 7.
    THE REQUIREMENTS OFDNA DATA STORAGE TTCATG… 0100011… TTCATG… 0100011… The requirements of ANY data storage device
  • 8.
    Some numbers: - Eachnucleotide = 0.34Å (0.34x10-9 m) - Each cell = 6 billion nt (6x109) = 1.8 m DNA - Each human = 3.72x1013 cells DNA STRUCTURE AND COMPOSITION What is this thing called DNA? Deoxyribonucleic acid, structure and function
  • 9.
    …G A TT A C A… … G A T T A C A … … 1 0 0 0 0 1 0 … A, T = 0 C, G = 1 Shannon information capacity of DNA = 1 (More flexibility in coding) DNA *IS* A DIGITAL DATA STORING SYSTEM Depending on the encoding method, we can achieve different capacities (Shannon information capacity index calculation for DNA) Erlich Y et al, Science 2017
  • 10.
    …G A TT A C A… … G A T T A C A … …10 00 11 11 00 01 00… A = 00 C = 01 G = 10 T = 11 Shannon information capacity of DNA = 2 (Biological constraints à ~1.58) DNA *IS* A DIGITAL DATA STORING SYSTEM Depending on the encoding method, we can achieve different capacities (Shannon information capacity index calculation for DNA # 2) Erlich Y et al, Science 2017
  • 11.
    DNA *IS* ADIGITAL DATA STORING SYSTEM Nature has its own ways of encoding information in DNA (nucleotide triplets=aminoacids)
  • 12.
    Erlich Y etal, Science 2017 DNA Fountain à Densidad de información: 215 PB/g DNA DNA *IS* A DIGITAL DATA STORING SYSTEM DNA Fountain, or how to store ALL the information in just one minivan
  • 13.
    Erlich Y etal, Science 2017 DNA Fountain? The arrival of a train at La Ciotat, 1896 EXCHANGING INFORMATION USING DNA: HIGH FIDELITY DNA Fountain, does it work, really? Spoiler: yes, it does!
  • 14.
    Hoshika S etal, Science 2019 Nature 566, 436 (2019) 4 SYNTHETIC BASES TO EXPAND THE CODING POTENTIAL OF DNA DNA constraints, Do we have enough with just FOUR letters? Let’s make some more!
  • 15.
    Kate Rubins, NASA,2016 SEQUENCING DNA IS READING IN A FOUR LETTER ALPHABET Sequencing modalities, speed and precission: With nanopore technologies, sequencing needs just an USB drive-like device
  • 16.
    THE PRICE OFSEQUENCING: PLUMMETTING SINCE 2001 Sequencing DNA, Can we really afford this? The cost of sequencing, then and now.
  • 17.
    Erlich Y etal, Science 2017 Veces que se podría reproducir “Despacito” 1.5x1015* (* tal vez más) HOW MANY TIMES CAN WE RETRIEVE DATA FROM THE SAME DNA FILE? How many times can we reproduce data from DNA? The “Despacito” Paradigm – we can have as much as we need
  • 18.
    1 Ma 12Ka 5 Ka PLEISTOCENO H.Neol HOLOCENO DNA IS ***VERY*** STABLE Time Scale of DNA stability …It really lasts long
  • 19.
    DNA IS ***VERY***STABLE Yuka mammoth ~28.000 years Yamagata et al Sci Rep 2019 Time Scale of DNA stability …It really lasts long
  • 20.
    Time Scale ofDNA stability …and some cool stuff that has been successfully sequenced !
  • 21.
    A (POTENTIAL) DNA-BASEDTIME CAPSULE Svalbard Global Seed Vault Arctic World Archive DNA STORAGE ONLY REQUIRES (SOME) COLD
  • 22.
    Arctic World Archive (PIQL) GUESSWHOSE INFO STORAGE STRATEGY IS “PICKLED”? Current strategies to preserve data are “pickled” i.e., they didn’t use DNA but photographic film L
  • 23.
    1970s 1980s 1990s2000s THE EVOLUTION OF DATA STORAGE PARALLELS THAT OF CHER’S HAIRSTYLE You can change your style, but you can’t change your soul Things become eventually obsolete and useless -but DNA àAs long as there are human beings, we’ll be able to read DNA data
  • 24.
    …ABOUT THIS THINGIN YOUR TRUNK?? “Have some pickles innit, mate?”
  • 25.
    Organick L etal, Nat Biotechnology 2017 Vs. RANDOM ACCESS CAN BE EMBEDDED IN THE ENCODING METHOD …About random access…it’s just proper encoding!
  • 26.
    DNA-based Magnetic-based 2019 Costperbit ??? =$7000 MAKE DNA (GREATAGAIN) Eventually, the costs of DNA synthesis will match or surpass magnetic data recording
  • 27.
    CRISPR molecular recording OR:can we make living recorder organisms using their DNA and CRISPR?
  • 28.
    Francis Mojica THE ORIGINSOF CRISPR ARE IN ALICANTE (NOT A JOKE!) The discovery of CRISPR and the importance of basic research
  • 29.
    PublicationsPerYear 4000 3000 2000 1000 0 2018 2010 2015 2016 2017 2014 2013 2012 2011 2004 2009 2008 2007 2006 2005 CUSTOM (FAST, PRECISE) GENOMEMANIPULATION CRISPR IS TO GENOME EDITING LIKE QUANTUM IS TO COMPUTING Some ethics involved here, don’t edit your babies at home (or your lab) See Lluis Montoliu for reference @LluisMontoliu
  • 30.
    Source: The DoudnaLab (www.doudnalab.org ) CRISPR IS A TWO-STEP BACTERIAL IMMUNITY MECHANISM How CRISPR was intended to be used in nature?
  • 31.
    Source: The DoudnaLab (www.doudnalab.org ) CRISPR IS A TWO-STEP BACTERIAL IMMUNITY MECHANISM
  • 32.
    Foronda et al,Unpublished Tang W et al, Science 2018 GENOME EDITING CAN BE TRACED: A SIMPLE MOLECULAR RECORDER CRISPR as molecular recorders of different sorts – including from our lab!
  • 33.
    Source: The DoudnaLab (www.doudnalab.org ) CRISPR IS THE BLOCKCHAIN OF BACTERIAL IMMUNITY
  • 34.
    “Pixets” are setsof pixels encoded in oligonucleotides Where the 1st 4 nucleotides encode pixet ID, position within the oligont encodes pixel positions and triplets encode gray scale
  • 35.
    Acquiring pixets alonga time frame resolves into a GIF!
  • 36.
    Encoded GIF (36x26pixels) Human and animal locomotion (Eadweard Muybridge) Frame 1 Frame 2 Frame 3 Frame 4 Frame 5 RECORDING GIFS IN BACTERIAL POPULATIONS
  • 37.
    IMAGEN ORIGINAL RECONSTRUCCIÓN APARTIR DE BACTERIAS Source: Shipman SL et al, Science 2016 Shipman SL et al, Nature 2017 RECORDING GIFS IN BACTERIAL POPULATIONS Acquiring pixets along a time frame resolves into a GIF! WARNING: real data J
  • 38.
    Molecular machines Molecular machinesfor embedded computational functions
  • 39.
    DNA ORIGAMI ASA SCAFFOLDING FOR BIOLOGICAL MACHINES DNA origami: Why fold DNA into specific structures?
  • 40.
    Rothemund, Nature 2006 DNAORIGAMI AS A SCAFFOLDING FOR BIOLOGICAL MACHINES DNA origami requires a lot of computation (and design!)
  • 41.
    Chao et al,Nature Materials 2018 Chatterjee et al, Nature Nanotech, 2017 SINGLE-MOLECULE DNA NAVIGATORS Example: single-molecule DNA navigators to solve mazes…
  • 42.
    DNA ORIGAMI-BASED MAZES– like nodes in a graph …because each node in the maze can be visualized as a graph node (decision tree)…
  • 43.
    Chao et al,Nature Materials 2018 PARALLEL-DEPTH FIRST SEARCH USING DNA NAVIGATORS …allowing us to solve the maze by retrieving ALL THE POSSIBLE SOLUTIONS AT ONCE (how about that, quantum computing?)
  • 44.
    SI TE HASDORMIDO EN LA CHARLA: 1.- El DNA ES un Sistema de almacén digital de datos estable, robusto y energéticamente eficiente (y caro) (por ahora) 2.- CRISPR sirve como grabadora molecular analógica y digital (además de muchas otras cosas) 3.- Los DNA navigators son capaces de PDFS, generando materiales moleculares con funciones computacionales embebidas DNA ROCKS!
  • 45.