Biomod/2012/Harvard/BioDesign/SpringBrainstorming: Difference between revisions

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== Conclusion==
== Conclusion==
* General Topics:
** MAGE (various applications) - Ian Choi
**DNA Walker (increase speed) - In Young
**DNA Origami (geometry, stability, restriction enzymes, limits) - Wes
**DNA Delivery (magnetic targeting, logic gates) - Val
**Modifying cell DNA (phage, scaffold, microbiome) Jacob
**Proof of concepts of In Vivo Ideas - Gina :)
<br>
*10 Bad ideas 10 Not so Good Ideas
**Creating the Veritas symbol out of DNA origami
**Train!!!! with passengers!!
**Fiddling with microbiome of living organisms to tailor synthesize specific compounds upon introduction of particles (like food)
**Better controlling DNA walkers by choosing start and end points (with specific DNA sequences)
**DNA minecraft / world!!
*More logistical details
**CadNano tutorials
**MatLab


=Meeting #1 (4/25/12)=
=Meeting #1 (4/25/12)=

Revision as of 17:14, 6 May 2012

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Meeting #2 (4/29/12)

Readings

  • A Logic-Gated Nanorobot for Targeted Transport of Molecular Payload [1]
  • Organization of Intracellular Reactions with Rationally Designed RNA Assemblies [2]
  • Synthetic Biology Moving into the Clinic [3]
  • A Tightly Regulated Molecular Motor Based upon T7 RNA Polymerase [4]
  • Programming cells by multiplex genome engineering and accelerated evolution [5]
  • Creation of a Bacterial Cell Controlled by a Chemically Synthesized Genome [6]

Brainstorm:

  • Valentina
    • Other applications of box structure using things like particles and logic gates? Continue last year’s project? Make a cascade?
  • Jacob
    • Let’s look at problems to solve, not necessarily applications of ideas
  • In Young
    • Use MAGE to create novel bacterial lines
    • Apply MAGE to photosensing - capturing light to create energy?
    • Using bacteria to make even higher-density fuels that are therefore more economical
  • Jacob
    • Seems like the MAGE process would be a lot of work
    • Using walkers seem interesting. Can we make them faster? We should make a DNA walker that can actually walk along microtubules. We know DNA can bind to microtubules. Interesting since they aren’t so sure ATP can be used.
    • It seems like the most successful things have been done by taking something from the cell and using it rather than trying to create something.
    • Train of DNA polymerases with Nyanocat passengers.
  • Gina
    • Interesting how the genomes we work with are too small.
    • Using a bigger genome? It seems like it would be useful.
  • Ian
    • Novel geometries attached at center forming sphere
    • Increasing sensitivity of boxes (sphere of boxes more effective than single)
    • DNA scaffolds inside cells
    • nanostructures (spikes that puncture cells) - insert DNA scaffolds or complementary-binding mRNA strands which can inhibit free-floating mRNA strands already found in the cell which are needed specifically by cancer cells and not by normal cells.
    • Is inserting into cell issue?
    • Scaffold to accelerate photosynthesis - accelerate assembly line (flow of electrons - could we accelerate this flow using DNA scaffold? treat it like a conductor?
  • Jacob
    • Phage/Virus with special RNA, the reverse transcriptase is used to create DNA, self-assembles inside cell. Synthetic life used to alter other cells?
    • Using DNA nanotech in multicellular organisms or even just eukaryotes
  • Jacob
    • Using magnetic field to activate or deactivate nanorobot? Maybe the magnetic field can be used to not just activate/deactivate but also to localize the DNA nanorobots in select places like cancer tumors. Use several magnets that spin around to create an undulating force which can make the nanorobots have rotary-like motions
  • Valentina
    • Using magnetics so that two particular units only bind to each other and create an activated unit.
  • Wesley
    • How long do DNA boxes last outside of the human body?
    • Testing how the geometry affects how this origami structure lasts in the body?
  • Ian
    • Tailored restriction enzymes to cut up an existing nanorobot?
    • One box releases restriction enzymes that cuts something else
  • In Young
    • Structures of varying stability
    • Need to amplify
  • Ian
    • Alter the microbiome so that weight-loss drugs produced in the gut can be artificially produced, production induced by food intake.
    • Weight loss is associated with stress-inducers or chemicals produced in times of dietary stress that thus accelerate fat burning (and the related system of proportional response). Can we make bacteria that produce these stress-response chemicals based on how much food the human eats?
  • In Young
    • Why not use MAGE to accelerate the evolution of fat-loss inducing organisms found in the microbiome
  • Ian
    • Use dna sequences to stop polymerase in its tracks
    • Making bacteria that can better design dna scaffolds
    • Use fluorescently labelled NTPS to create a new kind of sequencing
    • Using two part of gfp that are split apart and attached to two ends of the dna scaffold and fluoresce when they snap together
    • Using MAGE to accelerate the evolution of the human microbiome over a long period of time, what happens if you reinsert it into the human once you have a dna scaffold, put it into the cell, dunno what happens afterward? put that into a mage and see what happens, will the cells change? maybe hydrogen production increases? once you put the through evolution continuously, optimize that scaffold? selectively alter that scaffold, choose one with highest H2 production
    • Venter paper → synthetic cell. what happens when you put synthetic life into a machine?
  • Jacob
    • Objection: not evolution on entire genome, need to choose specific parts
  • In Young
    • Economic objection to constantly putting in this scaffold
    • More sustainable in-vivo: construction by transforming the origami sequence into the genome and using reporter genes for analysis
  • Ian
    • Insert into genome, have cell transcribe the part that is the scaffold
  • Wesley
    • Simpler concepts that can actually be achieved over a summer
    • Something with multiple stages of achievement in case we don’t achieve the entire goal realistically
    • Mechanism of logic gates
    • Develop logic gates → build a computer, encoder, already have AND gate, whole system, OR, XOR, more binding sites? what NOT means for biology

Conclusion

  • General Topics:
    • MAGE (various applications) - Ian Choi
    • DNA Walker (increase speed) - In Young
    • DNA Origami (geometry, stability, restriction enzymes, limits) - Wes
    • DNA Delivery (magnetic targeting, logic gates) - Val
    • Modifying cell DNA (phage, scaffold, microbiome) Jacob
    • Proof of concepts of In Vivo Ideas - Gina :)


  • 10 Bad ideas 10 Not so Good Ideas
    • Creating the Veritas symbol out of DNA origami
    • Train!!!! with passengers!!
    • Fiddling with microbiome of living organisms to tailor synthesize specific compounds upon introduction of particles (like food)
    • Better controlling DNA walkers by choosing start and end points (with specific DNA sequences)
    • DNA minecraft / world!!
  • More logistical details
    • CadNano tutorials
    • MatLab

Meeting #1 (4/25/12)

Readings


Challenges and opportunities for structural DNA nanotechnology [7]
Dynamic DNA nanotechnology using strand-displacement reactions [8]
Harnessing biological motors to engineer systems for nanoscale transport and assembly [9]

Brainstorm (bolded ideas spurred positive discussion about feasiblity):


Competition is open to any ideas at molecular level
Should be DNA related in the end for the presentation
DNA/RNA can be much more useful than cells/proteins
Anything done with simple proteins can be very huge though.
People use DNA not because it’s the best but because it was just what was available
Decide what exactly we want to do by mid or late May. Meet every week?
Meet this time next week
Cascade of boxes
In vivo is potentially feasible
Use logic and/or gates to self-assemble at high accuracy
How did you decide on last year’s project?
Box on chalkboard



Ian
Use DNA to hook proteins together?
Assembly within a cell?
Nanoparticle assembly with help of DNA?
Pop up assembly?
Plate gridded DNA with nanoparticles? Semiconducting? Model after graphene?
Pathogen filter?
Use the accelerated high-throughput evolution to create bacteria that can make DNA for you.
Use phages
Use bacteria
Use mages - use sixty-base DNA and put into cells.
Replaces some of the okazaki fragments
Pierce
Use an interior red flag with fluorescent tag that shows when assembly failed?
Separate bad ones with filter?
Magnetic nanobeads? Use them? Or use them to speed up assembly?
UV crosslinking as a new method for DNA origami?
Potential damage
We want them to assemble complementary though
Make buckyballs out of DNA?
Use DNA AND RNA together?
ATPase + DNA = robot?
How do you make it?
What does it do?
Use DNA nanostructures for sequencing? Somehow?
Biosensors?
Nanopores/protein pores for sequencing?
Attach magnet to DNA nanocargos and use a super magnet above patient to localize only around tumors
What is the crucial capability that we can add?
Top-down construction/deconstruction
Mingjie - not our field's advantage
Nanopores
Use DNA boxes to eat bacteria
Make perpetual loop cascade
Problem of error
Need to add stuff to keep powering... use ATP?
Magnetic tracks for DNA robots?
Use cloud computing to screen for dynamics of crosstalk
Spear cells


Gina
PRINT DNA structures
Good for making libraries


Wesley
DNA walkers - what’s the application?
Can we use enzymes?
ATP?
Light?
Electricity?
The nice thing is that they are programmable
But the main drawback is that they are very, very slow
Can we speed it up?
Can we use heat?
We are talking about often is DNA replication
Rate limiting step is often the biased random walk
Temperature-mediated walk based on how similar the DNA strands are
Problem is that it isn’t sustainable


Valentina
Artificial immune system
Can we do stuff in the cell?
How do we measure the success of our final outcome?
Concretely: Can we see technically correct outcomes?
How do we know it actually worked?
Imaging neurons in a zebrafish - any applications?


Mark
Nanobots
Some scientists made a computer that would play tic tac toe with RNA


Ian
Interfering with the mRNA found in cancer cells


Valentina
How do DNA computers work?
Logic


Ian
Using stochastic motion to power DNA nanorobots

Conclusion


Next time, come with five or six big ideas
Come up with four good ideas
Pros
Cons
What do you think is the most difficult part?
Then come up with ten really bad ideas and explain!
Can we read a few more reviews because they really help catalyze ideas?
Shawn’s nanorobot paper
Wikipedia articles
Meet next week and present

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