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FNANO 2014 Conference Day 3

Zvonimir Dogic talked about dynamic phenomena – things that move and change while consuming energy. Microtubules and microfilaments are useful systems to study… they can be observed directly. Kinesin doing some interesting sliding dynamics. I like that his movies have subtle timestamps in the upper left. His microscopy is so clean. I want to know what scope he was using and how it is maintained. He showed 1mm sized views with beautiful across-the-board quality. The focus stays perfect for a highly extended time. The depletion interaction – PEG exclusion – is a nice way to exclude things to the surface, for instance.

2014-04-22 11_28_15-Spontaneous motion in hierarchically assembled active matter - reprint_final_copFrom “Spontaneous motion in hierarchically assembled active matter,” Tim Sanchez, Daniel T. N. Chen, Stephen J. DeCamp, Michael Heymann and Zvonimir Dogic, Nature 491, 431-434 (2012). Scale bars are 20 um.

He showed great movies of microtubule bundles at interfaces forming an actively advexing chaotic gel. Capillary flow actually emerges from the system. The topic turned to the topology of liquid crystal defects which is a surprisingly universal aspect of mathematics.

Jonathan Doye talked about mechanical properties of DNA as modeled in a medium-grain simulation. The model is a simplified version of DNA that is still being improved to incorporate the finer features of DNA structure. But the coarse features – pairing, stiffness, etc. – are still useful. Including modeling origami and nanodevices like a walker. But one reasonable model conclusion was that mismatches can accelerate the rearrangement to the minimum. It looks lime this model might explain the some strange phenomena talked about at DNA19 by Niranjan Srinivas that showed an anomalously slow kinetic step in the strand displacement reaction.

Damien Woods talked about self-replicating nanostructures. He wanted to make a soup of DNA that could form into a long tubule, but would do so incredibly slowly unless there were little tubule seeds floating around. He then introduced some seeds; tubules grew. Even better, as they grew really big they could be made to break in half and thus create more tubes.

Carlos Castro showed some very dynamic 3D DNA origami structures which were very pretty. The assembled TEM movies make it seem very tangible. The structures could in principle be used to do some force spectroscopy by exploiting the entropic spring properties of ssDNA.

I was very happy to see Niranjan Srinivas from the Winfree lab give his talk on the kinetics of strand displacement. I have been trying to remember the details since DNA19. There are some anomalies in the rates of certain steps of toehold mediated strand displacement that are very counterintuitive. I gather that the issue is some subtle rearrangement that is captured by the models shown in Jonathan Doye’s talk.

Katherine Willets and Joel Harris talked about analyzing surface bound fluorescent DNA which was very informative. Making dyes that can be turned off is obviously very important. Inverse DNA-PAINT with temporary quenchers might be an interesting solution to some of the high-density issues that prevent good localization of the Gaussian centroid.

Ibuki Kawamata talked about some DNA crosslinked gels and showed some interesting results where a steel ball would be suspended on top of a gel, giving a quantitative readout of its degree of crosslinking. Could one analyze a movie of a steel ball falling through a gel (or use a magnetic sensor?) and compute the viscosity? That would be a pretty convenient viscometer.

 

FNANO 2014 Conference Day 2

 

Mike Ramsey talked about nanopores and nanochannels. Making these nano-analytical devices looks easy in his movies, but nanofabrication is no mean feat. Getting lithography to behave at the 100 nm level with enough reproducibility to do their experiments was very impressive. They used a channel that step-tapered. A single DNA molecule was threaded into that channel with an electric field. Then they looked at the apparent length in different channel widths. A reasonable person might run a bunch of DNA molecules through a bunch of different-width channels, but then you run into statistical averaging problems. Use the same molecule over and over and the physics pop out more simply. In narrower channels, the DNA must be straighter – no wiggling. That means it looks longer. The mathematical relationship between confinement and apparent length then pops out at a single-molecule level. They are also doing moderate vacuum (instead of very high vacuum) mass spectrometry. You know, because everyone wants a little MS on their bench. I know I do.

 

David Zhang talked about ultra-specific DNA probes. It’s a competition assay, not very sensitive, but coupled to PCR it allows for super bright, super simple single-nucleotide-mutation detection. Shana Kelly talked about some of the limitations in analyzing rare molecules in serum with back-of-the-envelope calculations to describe just how hard that is. They have some great high surface area nanodevices that help. Kevin Plaxo talked about electrochemical readout of DNA-DNA reactions which I think should definitely be coupled to the Zhang probes (and probably already are). Electrochemistry is super reliable in commercial products, so coupling it to these new bioassays is very smart. I love that they have a biochip that takes whole blood and looks for drugs in that blood-flow in real time. And they use a laminar flow system to keep the electrode from getting all saturated with cell debris which I think is brilliant.

 

I say a great talk about about releasable nano-DNA-icosahedra that encapsulate dextran FITC. I only caught the end of Peng Yin’s talk, but his ideas are all over the poster sessions including one on (if I understood correctly) inorganic nanoparticles from a DNA scaffold.

 

There was a nice talk by Hareem Maune on self assembling DNA origami-like structures on surfaces other than mica. I was interested to hear that the old stand-by APTES is a problem (amino propyl triethoxy silane). which I have used to functionalize glass before They prefer an imidazole silane which evidently chelates metals and pulls DNA onto the surface by bridging di-cations.

 

The last few talks included Nicholas Kotov talking about self-assembly of inorganic particles. One particularly interesting phenomenon generated monodisperse particles from polydisperse muilding blocks. It reminded me of the old fable of the big rocks and the sand. If you put big rocks into a jug first, you can pour in the sand on top. But if you put the sand at the bottom, you can not fit all the large rocks in on top of it. This is the same thing. Big particles come together and then build smaller particles into the cracks. The system maximizes surface interactions while minimizing surface charge and the whole thing finds a nice energy minimum with very uniform products.

 

Anders Okholm and Chun Geng talked about DNA containers from different perspectives. The former used origami cages while the latter used DNA crystals. Both got lively questions.

Conference on DNA Computing Liveblog 7

Yannick Rondelez explained his DNA toolbox. He uses enzymes; enzymes are rare at this conference. Polymerase and nickase can create a cycle of production of copies of a template. The copies can go on to prime other copying processes (including self-copying) and it can inhibit other copying processes. That’s a nice system for building reaction networks. That’s the toolbox. The computer takes target behavior, translates to a network, then to reactions, then to DNA.

What kinds of dynamic reaction systems can you make? You can make bistable, autoamplifying, cyclical, etc. What is really amazing is that you can evolve a reaction network in silico using a genetic algorithm! Then, you can make the stuff and show that a bizarre reaction network (like a square wave oscillator!). I gather he has not yet actually produced the square wave experimentally. It’s only 18 nucleotides, but hybridization/reaction rates need to be super-precisely defined, I expect. Then use a microfluidic droplet-based parameter space screening chip. That’s almost as good as an in vitro square wave oscillator.

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Recent Books and Competing Visions for the Future

Several months ago, I said I was starting in on Ray Kurzweil’s new book (How to Create a Mind). I had many deadlines and needed something motivational (I still have many deadlines and would like another motivational book, actually). I read it and I enjoyed it. Kurzweil is a leader in the AI field but more of a technology cheerleader outside of that field. For my purposes, that is fine. I just need some Grand Vision sometimes.

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Use 2-step verification

The moral of the following story is: use 2-step verification. If you need to log into you Gmail from a strange computer, make it call your cell phone and confirm it’s really you. It can do SMS or voice or you can carry a list of one-time-use verification codes. Oh, and use a special password on your key accounts.

Back in 2012 there was a terrible story in Wired about how a hacker broke into Mat Honan’s Gmail account and used that to gain access to all his other accounts. The goal of this hacking spree was to vandalize Mat’s twitter. However, to keep the game afoot as long as possible, they used his newly compromised online identity to get Apple to wipe Mat’s iPhone, iPad, and MacBook. Another great reason to own an apple product (remember: if you can’t open it, you don’t own it).

Too much of my life is wrapped up in my Google accounts to leave them at risk. How about you?

Cheers,

Peter