Transcript Digitally Programmed Cells

State university of New York at New Paltz
Electrical and Computer Engineering Department
Emerging Technologies
Dr. Yaser M. Agami Khalifa
Outlines
• Nanotech Goes to Work: DNA Computing
• Digitally Programmed Cells
• Evolvable Hardware
Definition
• Molecular nanotechnology: Thorough,
inexpensive control of the structure of matter
based on molecule-by-molecule control of
products and byproducts; the products and
processes of molecular manufacturing, including
molecular machinery.
Programmable Molecules
• The tweezers exploit the
complementary nature of the
two strands that make up the
famous double helix that is
DNA.
• A stretch of single-stranded
DNA will stick firmly to another
single strand only if their
sequences of bases match up
correctly.
How it Works
• The tweezers comprise three single
strands of synthetic DNA. Two
strands act as the arms; one strand
straddles the others and acts as a
kind of backbone and hinge holding
the whole V-shaped structure
together.



The tweezers comprise three single strands of synthetic DNA. Two
strands act as the arms; one strand straddles the others and acts as a
kind of backbone and hinge holding the whole V-shaped structure
together.
The arms extend far enough to leave a number of unpaired bases
dangling free beyond the backbone.
When a fourth DNA strand is added to the test tube, it grabs the
unpaired bases and zips the tweezers shut. Again, just a few bases are
allowed to hang unpaired, which permits a fifth strand to rip away the
Where is it going
• Dr Yurke said of his team's DNA tweezers: "This
may lead to a test-tube based nanofabrication
technology that assembles complex structures,
such as circuits, through the orderly addition of
molecules."
• The Bell Laboratories are already working to
attach DNA to electrically conducting molecules
to assemble rudimentary molecular-scale
electronic circuits.
How will nanotechnology improve our
lives?
• One of the first obvious benefits is the
improvement in manufacturing techniques. We
are taking familiar manufacturing systems and
expanding them to develop precision on the
atomic scale.
• Some of the most dramatic changes are
expected in the realms of medicine. Scientists
envision creating machines that will be able to
travel through the circulatory system, cleaning
the arteries as they go; sending out troops to
track down and destroy cancer cells and tumors;
or repairing injured tissue at the site of the
wound, even to the point of replacing missing
limbs or damaged organs.
• Nanotechnology is expected to touch almost
every aspect of our lives, right down to the
water we drink and the air we breathe. Once we
have the ability to capture, position, and change
the configuration of a molecule, we should be
able to create filtration systems that will scrub
the toxins from the air or remove hazardous
organisms from the water we drink. We should
be able to begin the long process of cleaning up
our environment.
What progress is being made today in
nanotechnology?
• Scientists are working not just on the materials
of the future, but also the tools that will allow
us to use these ingredients to create products.
Experimental work has already resulted in the
production of moleculat tweezers, a carbon
nanotube transistor, and logic gates.
• Theoretical work is progressing as well. James M.
Tour of Rice University is working on the
construction of molecular computer. Researchers at
Zyvex have proposed an Exponential Assembly
Process that might improve the creation of
assemblers and products, before they are even
simulated in the lab. We have even seen researchers
create an artificial muscle using nanotubes, which
may have medical applications in the nearer term.
Recent:Chemicals Map
Nanowire Arrays (Feb. ’04)
• One promising possibility for replacing today's
chipmaking technologies when they can no longer
shrink circuit size is arrays of nanowires whose
junctions form tiny, densely packed transistors.
• Harvard University and California Institute of
Technology researchers have devised a scheme to
chemically modify selected nanowire junctions to
make them react differently to electrical current than
the junctions around them.
• The chemical modification makes cross points more
sensitive to switching voltage than unmodified cross
points, making it possible to selectively address
nanowire outputs using far fewer control wires.
• This makes connecting nano components to ordinarysize circuits possible and is also a step toward
making the integrated memory and logic needed to
make a functional nanocomputer.
• Prototype memory and processors could be built
within two to five years, and commercial devices
within five to ten years, according to the researchers.
The research appeared in the November 21, 2003
issue of Science.
Recent Updates (Friday 2/6/04)
• Researchers from the University of California at
Berkeley and Stanford University have fabricated
a circuit that combines carbon nanotube
transistors and traditional silicon transistors on
one computer chip. Connecting minuscule
nanotube transistors to traditional silicon
transistors enables the atomic-scale electronics
to communicate with existing electronic
equipment.
Digitally Programmed Cells
Motivation
• Goal: program biological cells
• Characteristics
 small (E.coli: 1x2m , 109/ml)
 self replicating
 energy efficient
• Potential applications
 “smart” drugs / medicine
 agriculture
 embedded systems
Approach
high-level
program
logic
circuit
genome
microbial
circuit
compiler
in vivo chemical activity of genome
implements
computation specified by logic circuit
Key: Biological Inverters
• Propose to build inverters in individual cells
 each cell has a (complex) digital circuit built from inverters
• In digital circuit:
 signal = protein synthesis rate
 computation = protein production + decay
Digital Circuits
• With these inverters, any (finite) digital circuit can be built!
A
A
B
C
D
=
C
D
gene
C
B
gene
• proteins are the wires, genes are the gates
• NAND gate = “wire-OR” of two genes
gene
Components of Inversion
Use existing in vivo biochemical mechanisms
• stage I: cooperative binding
 found in many genetic regulatory networks
• stage II: transcription
• stage III: translation
• decay of proteins (stage I) & mRNA (stage III)
The majority of genes are expressed as the proteins they
encode. The process occurs in two steps:
•Transcription = DNA → RNA
•Translation = RNA → protein
Taken together, they make up the "central dogma" of
biology: DNA → RNA → protein
.
Stage I: Cooperative Binding
fA
input
protein
C
cooperative
binding
rA
repression
input
protein
C
 fA = input protein synthesis rate
 rA = repression activity
rA
(concentration of bound operator)
• steady-state relation C is sigmoidal
0
“clean” digital signal
fA
1
Stage II: Transcription
T
rA
yZ
transcription
repression
mRNA
synthesis
 rA = repression activity
 yZ = mRNA synthesis rate
• steady-state relation T is inverse
invert signal
T
yZ
rA
Stage III: Translation
L
yZ
fZ
translation
mRNA
synthesis
output
protein
mRNA
L
 fZ = output signal of gate
• steady-state relation L is mostly linear
fZ
yZ
scale output
Putting it together
signal
fA
input
protein
C
cooperative
binding
rA
repression
T
transcription
yZ
L
mRNA
synthesis
output
protein
input
protein

mRNA
inversion relation I :
fZ = I (fA) = L ∘ T

fZ
translation
I
∘ C (fA)
“ideal” transfer curve:
 gain (flat,steep,flat)
 adequate noise
margins
“gain”
fZ
0
fA
1
Inverter’s Dynamic Behavior
• Dynamic behavior shows switching times
[A]
[ active
gene ]
[Z]
time (x100 sec)
Connect: Ring Oscillator
• Connected gates show oscillation, phase shift
[A]
[B]
[C]
time (x100 sec)
Memory: RS Latch
_
R
=
A
_
S
B
_
[R]
_
[S]
[B]
[A]
time (x100 sec)
Limits to Circuit Complexity
• amount of extracellular DNA that can be
inserted into cells
• reduction in cell viability due to extra metabolic
requirements
• selective pressures against cells performing
computation
Challenges
• Engineer component interfaces
• Develop instrumentation and modeling tools
• Create computational organizing principles
 Invent languages to describe phenomena
 Builds models for organizing cooperative behavior
• Create a new discipline crossing existing
boundaries
 Educate a new set of engineering/biochemistry
oriented students
Evolvable Hardware
The EHW Controlled Prosthetic Artificial
Hand Project
• Conventional EMG(Electromyograph)-contorolled
prosthetic hands take almost one month until users
master the control of hand movements.
• The EHW controller, however, succeeded in reducing
such rehabilitation time drastically (about ten minutes!).
• The EHW for the hand adaptively synthesizes a pattern
recognition circuit which is tailored to each user,
because EMG has strong individual differences. A gatelevel EHW LSI is developed for this EMG hand.