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Introduction to Bioengineering BIOE/ENGR.80 Stanford University Spring 2020 Class Slides Day 11 29 April 2020 These slides are made freely available to the fullest extent possible. Any copyrighted images used herein are used in good faith subject to the fair use exception for education. Please contact [email protected] directly re: any copyright concerns.

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Page 1: Introduction to Bioengineering Stanford University Spring 2020 … · 2020-06-13 · Introduction to Bioengineering BIOE/ENGR.80 Stanford University Spring 2020 Class Slides Day 11

Introduction to BioengineeringBIOE/ENGR.80Stanford University

Spring 2020 Class Slides

Day 1129 April 2020

These slides are made freely available to the fullest extent possible. Any copyrighted images used herein are used in good faith subject to the fair use exception for education. Please contact [email protected] directly re: any copyright concerns.

Page 2: Introduction to Bioengineering Stanford University Spring 2020 … · 2020-06-13 · Introduction to Bioengineering BIOE/ENGR.80 Stanford University Spring 2020 Class Slides Day 11
Page 3: Introduction to Bioengineering Stanford University Spring 2020 … · 2020-06-13 · Introduction to Bioengineering BIOE/ENGR.80 Stanford University Spring 2020 Class Slides Day 11

https://www.nature.com/articles/s41587-020-0500-9

Plants that make their own light?!

Page 4: Introduction to Bioengineering Stanford University Spring 2020 … · 2020-06-13 · Introduction to Bioengineering BIOE/ENGR.80 Stanford University Spring 2020 Class Slides Day 11

https://www.nature.com/articles/s41587-020-0500-9

Plants that make their own light?!

Page 5: Introduction to Bioengineering Stanford University Spring 2020 … · 2020-06-13 · Introduction to Bioengineering BIOE/ENGR.80 Stanford University Spring 2020 Class Slides Day 11

https://www.nature.com/articles/s41587-020-0500-9

Plants that make their own light?!

Page 6: Introduction to Bioengineering Stanford University Spring 2020 … · 2020-06-13 · Introduction to Bioengineering BIOE/ENGR.80 Stanford University Spring 2020 Class Slides Day 11

https://www.nature.com/articles/s41587-020-0500-9

Trillion-fold less bright than 100w bulb?

I like glowing plantsI wish for brighter, more colors, control

What if we used bioengineering abstraction?

Page 7: Introduction to Bioengineering Stanford University Spring 2020 … · 2020-06-13 · Introduction to Bioengineering BIOE/ENGR.80 Stanford University Spring 2020 Class Slides Day 11

Dr. Jennifer Brophy (previous class)

Turn light on/off?At specific locations?

Different logic “gates” set their output values depending on their input values

Page 8: Introduction to Bioengineering Stanford University Spring 2020 … · 2020-06-13 · Introduction to Bioengineering BIOE/ENGR.80 Stanford University Spring 2020 Class Slides Day 11

How do we bioengineer genetic logic gates so that they are easy for others to use*?

*if we can do so for logic gates then we can likely do so for any sort of genetically-encoded device

The challenge of abstraction…

Page 9: Introduction to Bioengineering Stanford University Spring 2020 … · 2020-06-13 · Introduction to Bioengineering BIOE/ENGR.80 Stanford University Spring 2020 Class Slides Day 11

https://en.wikipedia.org/wiki/Synthetic_biological_circuit

AND gate (transcription-initiation based)

Page 10: Introduction to Bioengineering Stanford University Spring 2020 … · 2020-06-13 · Introduction to Bioengineering BIOE/ENGR.80 Stanford University Spring 2020 Class Slides Day 11

https://en.wikipedia.org/wiki/Synthetic_biological_circuit

OR gate (transcription-initiation based)

Page 11: Introduction to Bioengineering Stanford University Spring 2020 … · 2020-06-13 · Introduction to Bioengineering BIOE/ENGR.80 Stanford University Spring 2020 Class Slides Day 11

https://en.wikipedia.org/wiki/Synthetic_biological_circuit

NAND gate (transcription-initiation based)

Page 12: Introduction to Bioengineering Stanford University Spring 2020 … · 2020-06-13 · Introduction to Bioengineering BIOE/ENGR.80 Stanford University Spring 2020 Class Slides Day 11

https://en.wikipedia.org/wiki/Synthetic_biological_circuit

AND gate

Where we draw the “box” determines how easy/hard device will be to reuse

Page 13: Introduction to Bioengineering Stanford University Spring 2020 … · 2020-06-13 · Introduction to Bioengineering BIOE/ENGR.80 Stanford University Spring 2020 Class Slides Day 11

https://en.wikipedia.org/wiki/Synthetic_biological_circuit

AND gate (PoPS-based)

A common-signal carrier enables proper abstraction

Page 14: Introduction to Bioengineering Stanford University Spring 2020 … · 2020-06-13 · Introduction to Bioengineering BIOE/ENGR.80 Stanford University Spring 2020 Class Slides Day 11

PolymerasePolymerasePolymerasePolymerasePolymerasePolymerasePolymerase

(from any source)

(to any destination)

Polymerase Per Second(transcription elongation ‘current’)

Page 15: Introduction to Bioengineering Stanford University Spring 2020 … · 2020-06-13 · Introduction to Bioengineering BIOE/ENGR.80 Stanford University Spring 2020 Class Slides Day 11

Control Signal #1 Control Signal #2

T TPolymerasePolymerase

AND gate (transcription-elongation based)

Bonnet et al., Science, 2013

Page 16: Introduction to Bioengineering Stanford University Spring 2020 … · 2020-06-13 · Introduction to Bioengineering BIOE/ENGR.80 Stanford University Spring 2020 Class Slides Day 11

Control Signals

TPolymerasePolymerase

Bonnet et al., Science, 2013

XOR gate (transcription-elongation based)

Page 17: Introduction to Bioengineering Stanford University Spring 2020 … · 2020-06-13 · Introduction to Bioengineering BIOE/ENGR.80 Stanford University Spring 2020 Class Slides Day 11

Computer(Logic & Memory)

Can abstract and connect not only logic but sensing and actuation via PoPS

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Sensors

Environmental Inputs

ActuatorsOutputs, Activities, & Phenotypes

Page 18: Introduction to Bioengineering Stanford University Spring 2020 … · 2020-06-13 · Introduction to Bioengineering BIOE/ENGR.80 Stanford University Spring 2020 Class Slides Day 11
Page 19: Introduction to Bioengineering Stanford University Spring 2020 … · 2020-06-13 · Introduction to Bioengineering BIOE/ENGR.80 Stanford University Spring 2020 Class Slides Day 11

* Li & Cannon, J Bacteriol, May 1998, p. 2450-2458, Vol. 180, No. 9 (U. Mass. Amherst)

Page 20: Introduction to Bioengineering Stanford University Spring 2020 … · 2020-06-13 · Introduction to Bioengineering BIOE/ENGR.80 Stanford University Spring 2020 Class Slides Day 11

Protein Balloon DNA

Page 21: Introduction to Bioengineering Stanford University Spring 2020 … · 2020-06-13 · Introduction to Bioengineering BIOE/ENGR.80 Stanford University Spring 2020 Class Slides Day 11
Page 22: Introduction to Bioengineering Stanford University Spring 2020 … · 2020-06-13 · Introduction to Bioengineering BIOE/ENGR.80 Stanford University Spring 2020 Class Slides Day 11

Many thousand so-called BioBrick DNA parts.

Freely available.Today.

Page 23: Introduction to Bioengineering Stanford University Spring 2020 … · 2020-06-13 · Introduction to Bioengineering BIOE/ENGR.80 Stanford University Spring 2020 Class Slides Day 11

iGEM 2010

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Page 24: Introduction to Bioengineering Stanford University Spring 2020 … · 2020-06-13 · Introduction to Bioengineering BIOE/ENGR.80 Stanford University Spring 2020 Class Slides Day 11

Polymerase Per Second (PoPS) as common signal carrier for transcription-based devices

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Sensor AOutputInput

Actuator AInput Output

Functional composition... what should the “output” of any Sensor be so that it can connect with the “input” of any Actuator?

Actuator BInput Output

Actuator CInput Output

Actuator DInput Output

Sensor BOutputInput

Sensor COutputInput

Page 25: Introduction to Bioengineering Stanford University Spring 2020 … · 2020-06-13 · Introduction to Bioengineering BIOE/ENGR.80 Stanford University Spring 2020 Class Slides Day 11

https://www.allaboutcircuits.com/textbook/digital/chpt-3/logic-signal-voltage-levels/

Signal levels (standards) & digitization

Page 26: Introduction to Bioengineering Stanford University Spring 2020 … · 2020-06-13 · Introduction to Bioengineering BIOE/ENGR.80 Stanford University Spring 2020 Class Slides Day 11

You can make genetically-encoded molecular machines.

Doing so smartly requires going up and down our abstraction hierarchy (otherwise too complicated).

Most of these engineering approaches are entirely new to biology (i.e., this type of bioengineering is v. new).

Details include: Identifying and implementing device boundaries & common signal carriers.

Considering signal level matching & digitization/ amplification

Computer(Logic)

Sensors

Environmental Inputs

ActuatorsOutputs, Activities, & Phenotypes