John H. Reif
Spring Semester, 2024
Room LSRC A156
Textbooks:
·
[Douglas]: Kenneth Douglas, DNA Nanoscience: From Prebiotic
Origins to Emerging Nanotechnology, CRC Press, Edition 1, (2016) ISBN
9781498750127
· [Seeman]: Nadrian
Seeman, Structural DNA Nanotechnology, Cambridge University Press,
Edition 1, (2016), ISBN 9780521764483
SCHEDULE
Class |
Date |
Topics |
& Primary Lecture Notes |
Required Reading
|
Secondary Lecture Notes |
Lecture 1 |
Jan 11 |
Overview of DNA structure - DNA Overview - dsDNA secondary and tertiary structure -
DNA Hairpins - Base Stacking - DNA Hybridization & Duplex DNA - dsDNA Mechanical Properties DNA
Thermodynamics - Dependence
on temperature, salinity, magnesium - Steric hindrance -Nonstandard
DNA confirmations & DNA Structure Transitions: -B, A, and Z form DNA - DNA Structure Transitions: DNA B-Z transitions - DNA Triplex Conformations - G
Quadra-Complexes |
Overview of DNA Structure: Introduction to DNA
Structure
[PDF] [PPT]
|
Required
Reading: [Douglas] Chapters 1 & 2 |
|
Lecture 2 |
Jan 16 |
Coarse-Grain Modeling of DNA
Nanostructures and Reactions: Graph & Cartoon Models - Cartoon
models of DNA - Dot Bracket Notation For RNA & DNA
nanostructures |
|
Required
Reading: [Douglas] Chapters 1 & 2 |
Extra Reading: Programming
Biomolecular Selfassembly Pathways [PDF] [PPT] Programming Biomolecular Selfassembly Pathways Modeling DNA Nanodevices Using Graph Rewrite
Systems [PDF] [PPTX] |
Lecture 3 |
Jan 18 |
DNA Enzyme reactions: - Ligation, - Restriction enzymes - Helicase enzymes - Polymerization & Strand-displacing polymerases - Kinetic Models of DNA Enzymic Reactions] |
Enzyme Reactions on DNA [PDF] [PPTX] |
Required
Reading: [Douglas] Chapters 1 & 2 |
|
Lecture 4 |
Jan 23 |
Adleman’s
first demonstration of DNA Computation: [PDF] |
Adleman’s
first demonstration of DNA Computation: [PDF] |
|
Extra
Reading: |
Lecture 5 |
Jan 25 Homework
#1 Assigned |
DNA Computation using Restriction Enzymes Enzymic Molecular Finite State Automata (Shapiro) Molecular Doctor using Enzymic Molecular Finite State
Automata |
DNA Autonomous Computation using Restriction Enzymes: - Autonomous DNA Computation via Restriction Enzyme
Reactions Enzymic Molecular Finite State Automata (Shapiro) [PPTX] [PDF] |
|
Extra Reading: DNA Autonomous
Computation using Restriction Enzymes: [FSA Computation: Shapiro
Nature 2001 PPT] [More FSA Computation:
Shapiro PNAS 2003 PPT] [Stochastic FSA
Computation: Shapiro PNAS 2004] |
Lecture 6 |
Jan 30 |
The PCR DNA
amplification protocol Bracketed PCR Isothermal DNA
Amplification Protocols: - Rolling Circle PCR - Strand-Displacement PCR - RT-LAMP |
The PCR DNA amplification protocol [PDF] [PPTX] |
|
|
Lecture 7 |
Feb 1 |
DNA
Computation via Polymerase Reactions: - Whiplash PCR - Autonomous
Whiplash PCR |
DNA
Computation by Whiplash PCR [PPT] [PDF] |
[Simulating Whiplash PCR: Hagiya] Winfree’s use
of Whiplash PCR for Branching Programs [PPT] [PDF] Paper: [Whiplash PCR: Winfree] |
|
Lecture 8 |
Feb 6 1 page
Project Abstract Due |
Intro to
Molecular Robotics: Natural &
Re-Engineered Protein Molecular Motors - Molecular Robotics Principals - Brownian Ratchets & Quantum Ratchets - Natural Protein Molecular Motors: Polymerase, Myosin,
Kinesin, Polymerase |
Overview of
Natural Protein Motors Molecular
Ratchets for Protein Molecular Motors |
|
Optional
Reading: More on
Natural Protein Motors [PPT] [PPT] Molecular
Ratchets: Molecular
Ratchets for Protein Molecular Motors (Mokhtar) Details: [PDF] [Brownian Ratchet Motors: Elmer] [Feynman Notes V1 Ch46: Ratchet & Pawl] [Overviews of Brownian Ratchets] [Biophysics of Brownian
Ratchets: PPT] More on
Molecular Ratchets: [More Slides on Brownian Ratchets] Examples:
Myosin & Kinesin [Examples of Molecular Ratchets] -Quantum Ratchets
Surveys: |
Lecture 9 |
Feb 8 |
Non-Autonomous
Molecular Robots: Molecular DNA Robotics & Walkers via External
State Changes: - DNA Nanostructure Actuation using DNA B-Z transitions - PX Nanomechanical Devices - DNA Robotics using Duplex to Triplex Transitions |
Non-Autonomous
DNA Robotics via External State Changes: |
Required Reading: [Douglas] Chapter 9 [Seeman]
Chapter 8
DNA Structure Transitions: [DuplexTriplexTransition: Mao] DNA Mechanics: Papers on DNA
Walkers using external state changes: [DNA Biped Walking Device:
Sherman&Seeman] |
DNA
Nanostructure Actuation using DNA B-Z transitions [PX Nanomechanical Device: Seeman & Yan] Duplex to Triplex Transitions:[DuplexTriplexTransition: Mao] |
Lecture 10 |
Feb 13 |
Autonomous DNA
Robotics: Autonomous DNA
Robotics using Enzymes: Autonomous DNA Computation via
Restriction Enzyme Reactions - Autonomous Molecular Robotics
using Restriction Enzyme Reactions -
DNA Robotics using Polymerase -Mao’s Molecular Gears Autonomous DNA Robotics via DNA Hybridization: - Turberfield's Autonomous DNA Walker - Seeman's Piped Walker |
Autonomous DNA Robotics and Walkers [PDF][PPTX] |
Autonomous
Restriction Enzyme DNA Walker by Yin Reif: [Restriction Enzyme DNA
Walker Design: Yin] Autonomous Robot using Polymerase Sahu & Reif: [Polymerase DNA Transport: Sahu] Autonomous
Molecular Robotics using Restriction Enzyme Reactions Yin Reif
Restriction Enzyme DNA Walker: [Restriction Enzyme DNA Walker Experiments: Yin] [Restriction Enzyme DNA Walker Paper: Yin] [Restriction Enzyme DNA
Walker Turing Computation: Yin] Papers on Autonomous Robot
Restriction Enzyme DNA Walkers [Restriction Enzyme DNA Walker: Turberfield] [Restriction Enzyme DNA Walker: Yamamura] DNA Robotics via DNA Hybridization: - Autonomous Molecular Motors & Walkers using Hybridization Reactions [Autonomous DNA Walker: Turberfield] |
[Douglas] Chapter 9 [Seeman]
Chapter 8 |
Lecture 11 |
Feb 15 |
DNA Robotic
Devices & Applications: - Seeman’s Molecular Assembly Lines and Reaction
Factories - Quan’s Cargo Sorting via Random DNA Walkers - Yan & Reif’s Social DNA Nanorobots |
Autonomous DNA Robotics and Walkers [PDF][PPTX] |
Molecular Gears Quan’s Cargo Sorting via
Random DNA Walkers |
|
Lecture 12 |
Feb 20 |
DNA Nanostructures DNA Tiles - DNA crossovers junctions: Holliday junctions - T-junctions - DNA DX, TX tiles - Crossover (4 x 4 and Mao's) and Double Decker Tiles - Hexagonal Tiles - other novel tile types: Hao's Grid-tiles 2D DNA Lattices & Tubes - 2D DNA lattices - corrugation methods to flatten assembly - DNA Tubes 3D DNA
Lattices Seeman's tensegrity tiles & lattices |
|
Required Reading: [Douglas] Chapter 6 & 7 [Seeman] Chapters 1-7 |
|
Lecture 13 |
Feb 21 |
DNA
Nanostructures, Cont 3D DNA Bricks |
2D & 3D
DNA Lattices DNA Bricks [PDF] [PPTX] |
Required Reading: [Douglas] Chapter 6 & 7 [Seeman]
Chapters 1-7 |
|
Lecture 14 |
Feb 22 |
2D DNA Origami - 2D DNA Origami - Origami
design software -CADnano - other software 3D DNA Origami Shi’s Curved and 3D DNA Origami Han’s Curved and Circular DNA
shapes Modeling the
Self-Assembly of DNA Origami |
3D DNA Origami |
Required Reading: DNA Origami Primer [PDF] [Douglas] Chapter 8 [Seeman]
Chapter 9 Review of DNA Origami: Fan Hong, Fei Zhang, Yan Liu, and
Hao Yan, DNA Origami: Scaffolds for Creating Higher Order Structures, Chem. Rev., 2017, 117 (20), pp 12584–12640 DOI:
10.1021/acs.chemrev.6b00825 |
DNA Origami Rothemund
Supplemental caDNAno Design Software for DNA Origami - Shi Cadnano Tool
Design DNA Origami [PDF] DNA Nanotube induced
alignment of membrane proteins for NMR structure determination(Shi) |
Lecture 1 |
Feb 29 Homework
#1 Due Homework
#2 Assigned |
Aptimers & DNAzmes In vivo Evolution of Aptimers & DNAzmes DNA Robotics using DNAzymes: - Spiders: Autonomous Molecular Robotics using DNAzyme DNA Robotics and Computation using DNAzymes |
In-vivo Evolution & SELECT Protocols For -DNA&RNA Aptamers -DNA enzymes (DNAzymes) -RNA enzymes (Ribozymes) Molecular Robotics and Computation using DNAzymes |
Required
reading: DNAzymes: A general purpose RNA-cleaving DNA enzyme (Joyce) Mechanism and utility of an RNA-cleaving DNA
enzyme(Joyce) DNARobotics using DNAzymes: [Improved DNAzyme Motor: Klavins] - Spiders:
Autonomous Molecular Robotics using DNAzymes: |
Further
Reading on In vitro Selection of Aptamers &DNAzymes: In vitro selection of RNA molecules that bind specific ligands Systematic evolution of ligands by exponential enrichment Directed Evolution of an RNA Enzyme Nucleic Acid Enzymes (Ribozymes and Deoxyribozymes): In Vitro
Selection and Application Further
Reading on DNAzyme Devices: An Autonomous DNA
Nanomotor Powered by a DNA Enzyme[Mao] An improved autonomous DNA nanomotor [Klavins] |
Lecture 16 |
Feb 27 |
DNA Reaction Networks Fueled by Strand Displacement Catalytic
Gates & Cascades: - Winfree's Seesaw Gates - Yurke's DNA Catalytic Cascades - Zhang's DNA Reaction Networks and Allosteric DNA Catalytic Reactions - Soloveichi's DNA Chemical Kinetics |
DNA Hybridization Reactions Invention of Toehold
binding & Strand displacement:
Yurke-Turberfield DNA Tweezers [DNA Tweezer: Yurke & Tuberfield] DNA Reaction
Networks Fueled by Strand Displacement [PPTX][PDF] |
Required Reading: Example of Toehold binding & Strand displacement: Yurke-Turberfield DNA Tweezers [DNA Tweezer: Yurke & Tuberfield] [Douglas] page 166 [Seeman]
Chapter 8 DNA Reaction Networks Fueled by Strand Displacement: (1) [Seesaw Gates: Winfree] [DNA Catalytic Cascades:
Yurke Slides] (1) [Catalyzed
Metastable DNA Fuel: Seelig]
(2) [DNA Reaction Networks:
Zhang] (3) [DNA Catalytic Reactions: Zhang] (4) [Allosteric DNA Catalytic
Reactions: Zhang] (5) [DNA Chemical Kinetics:
Soloveichik] |
Intro: Analysis: Cardelli ‘s
DNA Strand Algebra |
Lecture 17 |
Feb 28 |
Kinetics Modeling - Introduction to Kinetics - Stochastic
Chemical Reaction Networks DNA
Hybridization Kinetics |
Primary Chemical Reaction Kinetics Lecture: Kinetics Overview: [PDF] [PPT]
DNA Hybridization Kinetics [PDF][PPTX] DNA Seesaw Gate Kinetics [PDF][PPTX] |
|
Optional Chemical Reaction Kinetics Lectures:
Optional Chemical Reaction Kinetics Lectures Applied to Biochemical Networks:
Detailed Reading on Kinetics: Vallance: [PDF] Extra Reading: Introducing Improved
Structural Properties and Salt Dependence into a Coarse-Grained Model of DNA DNA
hybridization kinetics: zippering, internal displacement and sequence
dependence On the
biophysics and kinetics of toehold-mediated DNA strand displacement Stochastic Simulation of the Kinetics of Multiple Interacting Nucleic Acid Strands |
Lecture 18 |
Feb 29 |
Kinetic Software for Simulation of DNA Hybridization
Reactions - Probabilistic Model Checking & PRISM software |
Kinetic Simulation of DNA Nanostructures: -
coarse-grained models of DNA, - other
model and simulation techniques, - the
biophysical basis of toehold-mediated strand displacement Multistrand
(Caltech) [PPTX] [PDF] Visual DSD (Cambridge Microsoft) [PPTX] [PDF] Visual DSD
Modeling Leaks in DNA Strand Displacement Circuits & Shadow Cancelation [PPTX][PDF] In Class
Activities: Design and
Simulate a Simple DNA Strand Displacement Reaction Network [PDF] Solution to in-class exercises [PDF] |
Required Reading: Multistrand(Caltech) Schaeffer Master Thesis: Stochastic Simulation of the Kinetics of Multiple Interacting DNA Strands Visual DSD
(Microsoft Cambridge UK) Visual DSD: a design and analysis tool for DNA strand displacement
systems Design and analysis of DNA strand displacement devices using
probabilistic model checking Extending
Visual DSD Modeling Leaks in DNA Strand Displacement Circuits: Automated Leak Analysis of Nucleic Acid
Circuits(Zarubiieva&Philips,ACS Synth. Biol. 2022) Shadow
Cancelation: |
Extra Reading: Introducing Improved
Structural Properties and Salt Dependence into a Coarse-Grained Model of DNA DNA
hybridization kinetics: zippering, internal displacement and sequence
dependence On the
biophysics and kinetics of toehold-mediated DNA strand displacement Stochastic Simulation of
the Kinetics of Multiple Interacting Nucleic Acid Strands DNA Systems Modeling: |
Lecture 19 |
March 5 |
Thermodynamics and Kinetic Simulation of DNA
Nanostructures - Kinetics simulation methods |
OxDNA: Coarse-graining
DNA for simulations of DNA nanotechnology A Primer on the oxDNA Software Simulation Model of DNA [PPT] [PDF] |
OxDNA Coarse-graining
DNA for simulations of DNA nanotechnology |
Reference Papers: Reference Papers on DNA Thermodynamics & Kinetics Other Suggested Text Books on Kinetics P. W. Atkins, Physical Chemistry
M. J. Pilling and P. W. Seakins, Reaction Kinetics,
K. J. Laidler, Chemical Kinetics
B. G. Cox, Modern Liquid Phase Kinetics |
Lecture 20 |
March 6 |
DNA Hybridization Reactions using DNA Hairpins: (1) Pierce's Hybridization Chain Reaction (2) Turberfield's DNA Hairpin Fueling Devices (3) Winfree's
DNA Hairpin Hybridization |
DNA Hybridization Reactions using DNA Hairpins: Solution-Based DNA Hairpin Hybridization Reactions: [PPTX][PDF] (1) Hybridization Chain
Reaction: Pierce (2) Turberfield's DNA Hairpin Fueling Devices (3) Winfree's
DNA Hairpin Hybridization |
Required Reading: [Douglas] page 166 Papers on DNA Hybridization Reactions using DNA Hairpins: Catalytic
Hybridization Reactions (1) [Hybridization Chain Reaction: Pierce] (2) [Catalyzed Metastable DNA
Fuel: Seelig] (2) [DNA Hairpin Fueling
Devices: Turberfield] |
On the biophysics and kinetics of toehold-mediated
strand-displacement (Sudhanshu) Catalytic Hybridization Reactions for Detection: [Hybridization Chain Reaction: Pierce] Niranjan Srinivas PHD Thesis: Programming chemical kinetics: engineering dynamic
reaction networks with DNA strand displacement |
Lecture 21 |
March 7 Homework
#2 Due Homework
#3 Assigned |
Localized
Hybridization Reactions - on Nanotracks - on DNA origami - on cell membranes |
Localized DNA Hybridization Reactions using Hairpins: [PPTX][PDF] - On 1D DNA
Nanostructures (Nanotracks) - On DNA Origami - On Cancer Cell Membranes Localized DNA
Hybridization Reactions on Cell Membranes: [PPTX][PDF] |
Required Reading: Probabilistic Analysis of Localized DNA Hybridization Circuits Local Hybridization Chain-Reactions on the Surface of DNA Origami |
Extra
Reading: Protection
of DNA from Degradation in Serum and the Cell: DNA nanotechnology from
the test tube to the cell(Seelig, 2015) DNA topology influences
molecular machine lifetime in human serum Modified
deoxyoligonucleotides stable to exonuclease degradation in serum |
|
Week of March 11 |
No Class -
Spring BREAK |
|
|
|
Lecture 22 |
March 19 Homework
#1 Due March 19 Homework
#2 Assigned Due April 2 3 Page
Project Summary Due April 2 |
DNA Photonics - Fluorescent
labels - Fluorescence
resonance energy transfer (FRET) - Quantum dots Plasmonics -Plasmonics of
Metallic Nanoparticles -Optically-induced cutting of
DNA |
Fluorescence & Plasmonics Study Guide [PDF] Plasmonics [PDF] |
|
|
Lecture 23 |
March 20 |
Super Resolution Imaging Original Super Resolution Techniques DNA paint used for Super Resolution Imaging -Exchange DNA paint -Strand Displacement DNA paint Imaging in Cells via DNA Nanotechnology |
|
- |
|
|
Extra readings
|
Molecular Imaging and Quantification Gel Electrophoresis AFM Imaging SEM Imaging STM Imaging |
Molecular Imaging and Quantification -AFM Imaging [PPT(Grutter)] -SEM & TEM Imaging [SEM&TEM] -STM Imaging [PPT(Grutter)] |
[Seeman]
Chapter 5 |
-AFM Imaging PDF(Kronenberger)] -STM Imaging [PPT(Grutter)] |
Lecture 24 |
March 20 |
Cryo-EM |
Cryo-EM: 3D Molecular Microscopy [Cryo-EM] |
|
|
|
Extra readings |
Gel Electrophoresis |
- Gel Electrophoresis [Agarose gel electrophoresis of DNA (Michael E. Clark)] [Agarose gel electrophoresis of DNA (Michael E. Clark)] |
|
|
Lecture 25
|
March 21 |
Tile Complexity of Deterministic Assembled Shapes - Tile
Complexity of Assembled Squares - Exact Squares - Approx Square -Linear Structures Tile Complexity of General Shapes Tile Complexity of Randomized Assembly - Exact Shapes - Approx Shape -Linear Structure |
Tile Complexity of Assembly of Squares and
Linear Structures [PPTX] [PDF] |
Required Reading: -Deterministic
Tile Complexity Assembled Squares [Tile Complexity Assembled
Squares: Rothemund] - Deterministic
Tile Complexity of Assembling Shapes: [Complexity Assembled Shapes: Winfree] |
-Deterministic
Tile Complexity Assembled Squares [Tile Complexity Assembled
Squares: Rothemund] Exact Det. Tile Complexity of Squares: [Tile Complexity Assembled
Squares: Adleman] - Approximate Squares [Assembly of Approx Square
Tilings Chandran] -Randomized
1D Assembly [Tile Complexity of Linear
Assemblies: Chandran] [PPT] [PDF] -Randomized Tile Complexity of Assembling Shapes: [Randomized Assembly Exact Shapes: Doty]
[Randomized Assembly Approx Shapes: Schellerr] |
Lecture 26 |
April 2 Preliminary Full Project Draft
Due |
Assembly Error-Correction - Assembly
Error-Correction via Proofreading - Compact
Assembly Error-Correction: -
Error-Correction Lower Bounds - Self-Healing - Invadable Self-Assembly - Reversible Self-repair |
Tile Assembly
Error-Correction: via Proofreading,
Snaking & Redundancy [PDF] [PPTX] |
Required Reading: Assembly
Error-Correction via Proofreading: [Proofreading Tile Sets:
Winfree] - Compact
Assembly Error-Correction: [Compact Error Resilient
Assembliy: Reif] Reducing Facet
Nucleation |