dna computing and robotics: engineering (science?), fun, and applications milan n. stojanovic nsf...
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DNA Computing and Robotics:
Engineering (Science?), Fun, and Applications
Milan N. StojanovicNSF Center for Molecular Cybernetics
Department of MedicineColumbia University
Suppose we have a set of primitives:
Sensor primitives: Computing primitives: Moving primitives:
? ? ?
??
?
Recipe for Computing Primitives:
ACAA
TGGA
CACA
TTGA
CTCT
AGA
Beacons (Tyagi and Kramer)
1. Take Recognition Regions,
2. Take Nucleic acid catalysts,
+ +
Phosphodiesterase (Joyce)
E S
Ligase (Szostak)
+ +
E S1
S2
+
0 1
3. And combine (for computing elements, at least) them in:
Cf. modular design (e.g. Breaker…)
0 1
I1
Stojanovic et al., ChemBioChem 2001Stojanovic et al., J. Am. Chem. Soc. 2002
0
50000
100000
150000
200000
250000
0 100 200 300 400t (min)
FU
Logic Gates: YES (Detector or Sensor Gate)
Joyce 1995, Breaker 1999, Tyagi, Kramer 1996
ACAA
TGGA
CACA
TTGA
TA C A C T FTrA
CTCTTC
TAGTGA
C
A
CG
G
GC
A GC
TC
GAA
T
AGAAG
G G
GA
CC
A
CG
G
GC
A GC
TC
GAA
T
AGAAG
CA TT AT AG CG CT
AGC
TA
TA
AT
AT
CG
TA
TA
TA
CACT
F
TrAG
AG
AGAG
R A*S*IA
TAT
ATGCTAGCAT
GA TA TG CA TG C
rAG
F
R
+
Cleavage
Inactive Form
Active Form
YES IA
A GG
AGG
IA
A
OF
S
IA
0 10 0
I2
I1I1
I20
I2
1
Switching Primitives (Logic Gates):
ANDNOT
0 00 01
I3 I3 I3
0
I3
00
I3
I2I2I1I1 I1
I2I1I2
Three-input Gates
c3
1
2
T
c2
1
3T
c1
2
3T
c1
3
2T
i1 i2 i3
SUM
i1ANDi2ANDi3
i1ANDNOTi2ANDNOTi3
i2ANDNOTi1ANDNOTi3
i3ANDNOTi2ANDNOTi1
i1ANDi2
1
2
F
1
3
F
i1ANDi3
3
2
F
i3ANDi2
i1 i2 i3
CARRY
Some demonstrations of molecular computing:
A. Full adder (Lederman et. al, Biochem. 2006) B. Maya-II (Macdonald et al. Nano Lett. 2006)
11 × 01 = 11 × 10 = 11 × 11 =
(3×1=3) (3×2=6) (3×3=9)
01 × 01 =
(1×1=1)
01 × 10 =
(1×2=2)
C. DNA Calculator (Macdonald) D. AND Hub with Beads (Rudchenko)(Yashin et al. JACS ~2007)
10A
7AND9 D10
7AND9 D10
6D7
3 41 25
3AND4A->D5
1D3 2D45A
Implementation of Naughts-and-Crosses Playing Algorithm with Deoxiribozymes: Molecular Array of YES and ANDANDNOT Gates (MAYA)
Stojanovic, Stefanovic, Nat. Biotech. 2003
9
7
4
7
8
4
4
6
9
1
2
6
1
7
6
1
6
4
9
6
7
2
7
9
1
8
9
1
2
6
7
9
2
1
4
2
9
4
3
9
4
7
9
4
8
9
1
3
6
1
8
6
1
9
6
6
8
7
6
9
7
1
4
F
X
Mg2+
-1
0
1
2
3
4
1 2 3 4 5 6 7 8 9
Wells
F
9
7
4
7
8
4
4
6
9
1
2
6
1
7
6
1
6
4
9
6
7
2
7
9
1
8
9
1
2
6
7
9
2
1
4
2
9
4
3
9
4
7
9
4
8
9
1
3
6
1
8
6
1
9
6
6
8
7
6
9
7
1
4
F
F
i4 i4 i4
i4i4i4
i4 i4 i4
XXOi4
-1
0
1
2
3
4
1 2 3 4 5 6 7 8 9
Wells
F
9
7
4
7
8
4
4
6
9
1
2
6
1
7
6
6
7
2
7
9
1
8
9
1
2
6
7
9
2
1
4
2
9
4
3
9
4
7
9
4
8
9
1
3
6
1
8
6
1
9
6
6
8
7
6
9
7
1
4
F
F
i4 i4 i4
i4i4i4
i4 i4 i4
i9 i9i9
i9 i9
i9 i9
i9
4
9F
i9
XX
OO
X
-1
0
1
2
3
4
1 2 3 4 5 6 7 8 9
Wells
F
i9 XXO
O
X
X
O
9
7
4
7
8
4
4
6
9
1
2
6
1
7
6
6
7
2
7
9
1
8
9
1
4
2
9
4
3
9
4
7
9
4
8
9
1
3
6
1
8
6
1
9
6
1
4
F
F
i4 i4 i4
i4i4i4
i4 i4 i4
i9 i9i9
i9 i9
i9 i9
i9
4
9F
i9
9
2
1
i2 i2 i2
i2 i2 i2
i2i2 i2
F
-1
0
1
2
3
4
1 2 3 4 5 6 7 8 9
Wells
F
i2
MAYA vs. Milan: Losing Game
Zn2+
The Simplest Moving Primitive:
Zn2+
But, what about multivalent design?
Pei et. al JACS, 2006
AFM Images of Spider at Starting Point
Kyle Lund, Hao Yan, video now: with Nadine Dabby, Erik Winfree
AFM images of Spider on Lanes of Substrates
Kyle Lund, Hao YanVideo with: Nadine Dabby, Erik Winfree
START
END
Center for Molecular Cybernetics Phase II?
A
B
C
D
START
START
END
A
B
END
Center Members & Friends
• Erik Winfree (CS)• Hao Yan (CHE)• Niles Pierce (ApM)• Paul Krapivsky (Phys)• Sergei Rudchenko (BPh)• Nils Walter (CHE)• Milan Mrksich (CHE)• Darko Stefanovic (CS/EE)• Milan Stojanovic (MEDSci)• Nadrian Seeman (CHE)
• Henry Hess (CHE/MATS)• William Shih (CHE)• Srboljub Mijailovich (ME)• Natasha Yonoska (MATH)• Satoshi Murata (CS/ME)• Friedrich Simmel (P-CHE)• Vojislav Stojkovic (CS)• Qiao Lin (ME)• Paul Rothemund (CHE/CS)
CHE
0533096
CHE
0533096
Chemical Bonding Center NSF (CHE-0533096)
• Postdocs: Steven Taylor, Renjun Pei, Dmitry Kolpashchikov, Joanne Macdonald• Tech’s: Stanka Semova, Erik Green, Payal Pallavi, Ma Li• High Shool Program: Harvey Lederman, Yang Lee, Marko Sutovic, Kiran Pendri,
Wengho Lu, Kirill Lebedov, Srikanth Damera, George Lederman, Kaitlin Kyi. • Tiffany Elizabeth Mitchell• Collaborators:• Sergei Rudchenko (HSS), Ruslan Yashin• Darko Stefanovic (UNM), Mark Olah• Nils Walter (UM, Ann Arbor), Tony Manzo, Chamaree De Silva• Vincent Butler (Columbia)• Milan Mrksich (Chicago), Haim Tsubery• Erik Winfree (Caltech), Georg Seelig, Nadine Dabby• Hao Yan (ASU), Kyle Lund
Current funding NSF (ITR, 3xEMT, and CBC), JDRF, NIH (NCI-R21)Lymphoma and Leukemia Society Scholarship
Previously: NASA, NSF QuBIC, NSF Biophotonics, NIH (NIBIB), Searle
Acknowledgments:
M1
M2
Cell Type I
AND CellDeath
M1
Cell Type II
AND Spare Cell
B.A.M1
M2
Cell Type III
ANDC.
M3NOT
Spare Cell
NOT NOT
Glucose
GG
GG
+ Insulin
Negative Feedback
1. Cell-death by Boolean Calculations:
2. Glucose-triggered movement of catalytic nanoassemblies:
Potential practical applications: