Circuit Engineers Doing Biology Marc D. Riedel Assistant Professor, Electrical and Computer Engineering University of Minnesota Café Scientifique A 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

Bacterial Motor

Electron Microscopic Image

Nov. 20, 2007Marc Riedel, Café Scientifique8 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 ?  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 output protein

repressor protein 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, 2007Marc Riedel, Café Scientifique15 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, 2007Marc Riedel, Café Scientifique17 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. Circuits Biology

Nov. 20, 2007Marc Riedel, Café Scientifique19 Two Made-Up Facts [well, abstractions, really…] Logic Gates Biochemical Reactions +

Nov. 20, 2007Marc Riedel, Café Scientifique20 “AND” gate Logic Gates

Nov. 20, 2007Marc Riedel, Café Scientifique21 “XOR” gate Logic Gates

Nov. 20, 2007Marc Riedel, Café Scientifique22 inputsoutputs Digital Circuit circuit

Nov. 20, 2007Marc Riedel, Café Scientifique23 inputsoutputs circuit gate Digital Circuit

Nov. 20, 2007Marc Riedel, Café Scientifique24 NAND OR AND NOR Digital Circuit

My PhD Dissertation [yes, in one slide…]

circuit 0 1 Characterize probability of outcomes. inputsoutputs Model defects, variations, uncertainty, etc.: Current Research

circuit inputsoutputs 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,… p 1 = Prob(one) p 2 = Prob(one) Current Research

circuit inputsoutputs Model defects, variations, uncertainty, etc.: Current Research

Nov. 20, 2007Marc Riedel, Café Scientifique30 Biochemical Reactions cell proteincount

Nov. 20, 2007Marc Riedel, Café Scientifique31 Biochemical Reactions slow medium fast

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 n

M Exponentiation givenwant (m)(m)(n)(n) Use working types a, b, n sets n to one let a be non-zero nana   fast 2 med a let b be zero sets n to M 2 bm slow nbnb  2 v.fast b nn med.

Nov. 20, 2007Marc Riedel, Café Scientifique35 Bacteria are engineered to produce an anti-cancer drug: Design Scenario drug triggering compound E. Coli

Nov. 20, 2007Marc Riedel, Café Scientifique36 Bacteria invade the cancerous tissue: cancerous tissue Design Scenario

Nov. 20, 2007Marc Riedel, Café Scientifique37 cancerous tissue The trigger elicits the bacteria to produce the drug: Design Scenario Bacteria invade the cancerous tissue:

Nov. 20, 2007Marc Riedel, Café Scientifique38 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, 2007Marc Riedel, Café Scientifique39 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, 2007Marc Riedel, Café Scientifique40 cancerous tissue Approach: elicit a fractional response. Design Scenario

Nov. 20, 2007Marc Riedel, Café Scientifique41 produce drug triggering compound E. Coli Approach: engineer a probabilistic response in each bacterium. with Prob. 0.3 don’t produce drug with Prob. 0.7 Synthesizing Stochasticity

Nov. 20, 2007Marc Riedel, Café Scientifique42 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, 2007Marc Riedel, Café Scientifique43 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. X Y

Nov. 20, 2007Marc Riedel, Café Scientifique45 Engineering vs. Biology vs. Mathematics Dilbert Beaker Papa

It’s not a bug, it’s a feature.

Jargon vs.Terminology “Now this end is called the thagomizer, after the late Thag Simmons.”

Communicating Ideas

Domains of Expertise Vision Language Abstract Reasoning Farming Human Circuit Number Crunching Mining Data Iterative Calculations

Nov. 20, 2007Marc Riedel, Café Scientifique50 “ 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 “T hat the astonishing hypothesis is astonishing.” – Christophe Koch, 1995 The Astonishing Part

Circuits & Computers as a Window into our Linguistic Brains Circuit Brain Conceives of circuits and computation by “applying” language. Lousy at all the tasks that the brain that designed it is good at (including language). ?

If You Don’t Know the Answer…