circuit engineers doing biology marc d. riedel assistant professor, electrical and computer...
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Circuit Engineers Doing BiologyCircuit Engineers Doing Biology
Marc D. RiedelAssistant Professor, Electrical and Computer Engineering
University of Minnesota
Café Scientifique
A Discourse on the Changing Landscape of Scientific ResearchA Discourse on the Changing Landscape of Scientific Research
Hosted by the Bell Museum of Natural History
At the Bryant-Lake Bowl
“Minnesota Farmer”
• Most of the cells in his body are not his own!
• Most of the cells in his body are not even human!
• Most of the DNA in his body is alien!
Who is this guy?
“Minnesota Farmer”
• 100 trillion bacterial cells of at least 500 different types inhabit his body.
Who is this guy?
He’s a human-bacteria hybrid:
vs.
• only 1 trillion human cells of 210 different types.
[like all of us]
“Minnesota Farmer”
Who is this guy?What’s in his gut?
• 100 trillion bacterial cells of at least 500 different types inhabit his body.
He’s a human-bacteria hybrid:
vs.
• only 1 trillion human cells of 210 different types.
[like all of us]
About 3 pounds of bacteria!
What’s in his gut?“E. coli, a self-replicating object only a thousandth of a millimeter in size, can swim 35 diameters a second, taste simple chemicals in its environment, and decide whether life is getting better or worse.”
– Howard C. Berg
flagellum
Nov. 20, 2007 Marc Riedel, Café Scientifique 8
The (nano) Structural Landscape
“You see things; and you say ‘Why?’ But I dream things that never were; and I say ‘Why not?’"
– George Bernard Shaw, 1925
Novel Materials…
Novel biochemistry…
Novel biological functions…
The Computational Landscape“There are known ‘knowns’; and there are unknown
‘unknowns’; but today I’ll speak of the known ‘unknowns’.”
– Donald Rumsfeld, 2002
Semiconductors:exponentially smaller, faster, cheaper – forever?
1 transistor (1960’s)2000 transistors(Intel 4004, 1971)
800 million transistors(Intel Penryn, 2007)
The Computational Landscape
• Abutting true physical limits.
• Cost and complexity are starting to overwhelm.
“There are known ‘knowns’; and there are unknown ‘unknowns’; but today I’ll speak of the known ‘unknowns’.”
– Donald Rumsfeld, 2002
Semiconductors:exponentially smaller, faster, cheaper – forever?
The Computational Landscape
• Multiple cores?• Parallel Computing?
Potential Solutions:
“There are known ‘knowns’; and there are unknown ‘unknowns’; but today I’ll speak of the known ‘unknowns’.”
– Donald Rumsfeld, 2002
The Computational Landscape
b
a?
• Novel Materials?
Potential Solutions:
• Novel Function?
“There are known ‘knowns’; and there are unknown ‘unknowns’; but today I’ll speak of the known ‘unknowns’.”
– Donald Rumsfeld, 2002
gene
The Computational Landscape“There are known ‘knowns’; and there are unknown
‘unknowns’; but today I’ll speak of the known ‘unknowns’.”
– Donald Rumsfeld, 2002
RNAp outputprotein
repressorprotein
The Computational Landscape
gene
“There are known ‘knowns’; and there are unknown ‘unknowns’; but today I’ll speak of the known ‘unknowns’.”
– Donald Rumsfeld, 2002
RNAp
Biological computation?
nada
Nov. 20, 2007 Marc Riedel, Café Scientifique 15
Research Activities in my Lab
• The concurrent logical and physical design of nanoscale digital circuitry.• The synthesis of stochastic logic for robust polynomial arithmetic.• Feedback in combinational circuits.• High-performance computing for the stochastic simulation of
biochemical reactions.• The analysis and synthesis of stochasticity in biochemical systems.
Our research activities encompass topics in logic synthesis and verification, as well as in synthetic and computational biology. A broad theme is the application of expertise from the realm of circuit design to the analysis and synthesis of biological systems. Current projects include: ?
Nov. 20, 2007 Marc Riedel, Café Scientifique 17
Research Activities in my Lab
• We’re studying the mathematical functions for digital circuits. • We’re writing computer programs to automatically design such circuits.
• We’re studying the concepts, mechanisms, and dynamics of intracellular biochemistry.
• We’re writing computer programs for analyzing and synthesizing these dynamics.
CircuitsCircuits
BiologyBiology
Nov. 20, 2007 Marc Riedel, Café Scientifique 19
Two Made-Up Facts[well, abstractions, really…]
1x
2x
g
Logic Gates
Biochemical Reactions
+
Nov. 20, 2007 Marc Riedel, Café Scientifique 20
“AND” gate
0001
1x
2x
g0011
0101
1x 2x g
Logic Gates
Nov. 20, 2007 Marc Riedel, Café Scientifique 21
“XOR” gate
0011
0101
0110
1x
2x
g
1x 2x g
Logic Gates
Nov. 20, 2007 Marc Riedel, Café Scientifique 22
),,( 11 mxxf a
),,( 12 mxxf a
),,( 1 mn xxf a
inputs outputs
Digital Circuit
1x
2x
mx
circuit
Nov. 20, 2007 Marc Riedel, Café Scientifique 23
),,( 1 mn xxf a
),,( 11 mxxf a
),,( 12 mxxf a),,( 1 mxxf a
inputs outputs
1x
2x
mx
circuit gate
Digital Circuit
Nov. 20, 2007 Marc Riedel, Café Scientifique 24
1x
2x
3x
4x
5x
6x
NAND
OR
ANDAND
AND
NOR
1
0
0
1
1
1
1
0
1
0
0
1
Digital Circuit
circuit0
1
Characterize probability of outcomes.
inputs outputs
Model defects, variations, uncertainty, etc.:
Current Research
circuit
inputs outputs
Model defects, variations, uncertainty, etc.:
0,1,1,0,1,0,1,1,0,1,…
1,0,0,0,1,0,0,0,0,0,…
p1 = Prob(one)
p2 = Prob(one)
Current Research
Nov. 20, 2007 Marc Riedel, Café Scientifique 30
Biochemical Reactions
9
6
7
cellprotein count
+
8
5
9
Example: Exponentiation
“Every task will take twice as long as expected – even if the Riedelian Law of Productivity is taken into account.”
– That Great Procrastinator Riedel [midnight last night]
Riedelian Law of Productivity
n2222
n
M
ExponentiationM2given want
(m) (n)
Use working types a, b, n
sets n to onelet a be non-zero nana fast2
meda
let b be zero
sets n to M2
bmslow
nbnb 2v. fast
fastb
nn med.
Nov. 20, 2007 Marc Riedel, Café Scientifique 35
Bacteria are engineered to produce an anti-cancer drug:
Design Scenario
drugtriggering compound E. Coli
Nov. 20, 2007 Marc Riedel, Café Scientifique 36
Bacteria invade the cancerous tissue:
cancerous tissue
Design Scenario
Nov. 20, 2007 Marc Riedel, Café Scientifique 37
cancerous tissue
The trigger elicits the bacteria to produce the drug:
Design Scenario
Bacteria invade the cancerous tissue:
Nov. 20, 2007 Marc Riedel, Café Scientifique 38
cancerous tissue
Problem: patient receives too high of a dose of the drug.
Design Scenario
The trigger elicits the bacteria produce the drug:
Nov. 20, 2007 Marc Riedel, Café Scientifique 39
Design Scenario
• Bacteria are all identical.• Population density is fixed.• Exposure to triggering compound is uniform.
Constraints:
• Control quantity of drug that is produced.
Requirement:
Conceptual design problem.
Nov. 20, 2007 Marc Riedel, Café Scientifique 40
cancerous tissue
Approach: elicit a fractional response.
Design Scenario
Nov. 20, 2007 Marc Riedel, Café Scientifique 41
produce drug
triggering compound E. Coli
Approach: engineer a probabilistic response in each bacterium.
with Prob. 0.3
don’t produce drugwith Prob. 0.7
Synthesizing Stochasticity
Nov. 20, 2007 Marc Riedel, Café Scientifique 42
Generalization: engineer a probability distribution on logical combinations of different outcomes.
cell
A with Prob. 0.3
B with Prob. 0.2
C with Prob. 0.5
Synthesizing Stochasticity
Nov. 20, 2007 Marc Riedel, Café Scientifique 43
Generalization: engineer a probability distribution on logical combinations of different outcomes.
cell
A and B with Prob. 0.3
Synthesizing Stochasticity
B and C with Prob. 0.7
A with Prob. 0.3
B with Prob. 0.2
C with Prob. 0.5
Generalization: engineer a probability distribution on logical combinations of different outcomes.
cell
A and B with Prob. 0.3
Synthesizing Stochasticity
B and C with Prob. 0.7
Further: program probability distribution with (relative) quantity of input compounds.
)/()Pr( 1 YXfA
)/()Pr( 2 YXfB
)/()Pr( 3 YXfC
X
Y
Nov. 20, 2007 Marc Riedel, Café Scientifique 45
Engineering vs. Biology vs. Mathematics
Dilbert Beaker Papa
Domains of Expertise
• Vision• Language• Abstract Reasoning• Farming
Human
Circuit
• Number Crunching
• Mining Data• Iterative
Calculations
Nov. 20, 2007 Marc Riedel, Café Scientifique 50
“A person's mental activities are entirely due to the behavior of nerve cells, glial cells, and the atoms, ions, and molecules that make them up and influence them.”
– Francis Crick, 1982
Astonishing Hypothesis
“That the astonishing hypothesis is astonishing.”
– Christophe Koch, 1995
The Astonishing Part
Circuits & Computers as a Window into our Linguistic Brains
CircuitBrainConceives of circuits and
computation by “applying” language.
Lousy at all the tasks that the brain that
designed it is good at (including language).
?