Third Friday afternoon panel on Interfaces to DNA Computing and Molecular Programming

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Beckman Institute Auditorium, 3:00pm to 3:45pm, Friday.


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Contents

Deborah Fygenson

Towards a fundamental understanding of Molecular Biology

I see and I remember. I do and I understand.” This axiom of learning reminds us that understanding is more than knowledge. It is the ability to recreate what we witness. In molecular biology, reconstitution of an observed phenomenon from a minimal set of purified components is the “gold-standard”, demonstrating thorough knowledge of the material origins of the phenomenon. DNA nanotechnology presents a remarkable platform from which it may be possible to recreate phenomena heretofore unique to molecular biology from abiological components of rational design. Doing so would set a new “gold-standard”, demonstrating understanding of the physical basis for the phenomenon. Even if ultimately unsuccessful, the exercise will bring the physical landscape of molecular evolution into sharp relief, yielding fundamental insights into biomolecular design. We will discuss the range of phenomena most readily, or usefully, approached in this manner, and how this type of biological physics might influence the development of DNA computing and molecular programming.

Kurt Gothelf

For the past decade several chemistry research laboratories have used DNA for templating chemical reactions and for synthesizing libraries of molecules using combinatorial approaches. However, with the recent advances in DNA nanotechnology and molecular programming several new directions for chemistry research arises. (1) Algorithmic DNA systems may be used to control chemical synthesis and react to feedback of various stimuli. (2) Chemically engineered DNA nanostructures will provide higher stability in vivo and more advanced properties. Structures may be designed as encodable drug-delivery vehicles where logic operations controlled by DNA determine where and when the drug cargo is released. (3) Reliable deposition of large complex DNA structures such as DNA origami in CMOS based electronics platforms may allow for the integration of conductive molecules and materials. Single molecule conducting polymers may be integrated in DNA systems, to give a reliable and highly reproducible electronic handle to single organic and bioorganic molecules and other nanoscale electronic components. Thus, such methods may be of importance in reviving the field of molecular electronics, lead to single molecule biosensors and in turn provide an electronic readout of the results of DNA-based computations.

Paul Rothemund

Custom instruments for biology

When a physicist wants to ask a particular question of the universe, they construct a special purpose instrument to answer it. For example, a physicist might start with an optical work bench, a table with a bunch of screw holes in it, add to it a complicated arrangement of lasers, mirrors, lenses and other elements which prepares light of just the right kind to probe and manipulate the electronic states of an atom. When a biologist wants to ask a particular question, say concerning a proteins function, they typically act more like a detective who can perform deductions from a limited palette of queries: what is the molecular weight of a protein, how does it run in a gel, what happens when we mutate it, does it stick to this other protein and so forth. If you have problems with finding a reliable essay service that offers assistance not only with creating essays but term and research paper writing as well, I highly recommend you to visit BestWritingService.Com. One question is whether the use of DNA nanostructures can allow a biologist to work more in the mode of a physicist---to construct "custom built instruments" which probe exactly that aspect of a protein or cellular phenomena which the biologist wants to study. Seeman's proposal of using 3D DNA crystals as hosts for proteins to help determine their structure stands as the first such example of a custom instrument, but there will be many others. We will contemplate the range of ways in which DNA nanostructures might be used as custom instruments to probe biological phenomena.


Moving from Found Objects towards Purposeful Patterns

One of the key characteristics of "nanomaterials" is that they often exhibit exotic properties that are not exhibited in bulk versions of the material---exotic properties that promise new electronic or optical devices, vastly better computers or even "invisibility cloaks". Many of these properties depend on nanoparticles of a material being arranged in certain geometrical patterns. A common approach, for many physical scientists, is to spray a surface with random arrangements of a nanomaterial and look around for those configurations which should have the desired special property. For example a hexagon of nanoparticles might respond to a particular frequency of light, and the physicist would have to find a hexagon among a field of thousands of singletons, doublets, triplets and other clusters of nanoparticles. Thus in studying the exotic properties of nanomaterials we often rely on "found objects", particular arrangements that just happen to occur. Worse, if such found objects have wonderful properties we have no way to construct them in bulk to make a macroscopic material. DNA nanostructures provide a way to organize nanomaterials to purposefully create the nanoscale patterns that promise exotic properties. We will discuss a number of challenges facing this approach to creating nanoscale devices.


Christina Smolke

Advances in nucleic acid computing and molecular programming are helping to fuel the emerging area of RNA synthetic biology. Molecular computing strategies allow for the intriguing possibility of implementing computing in environments where standard silicon-based computers cannot go - specifically in living systems. The past few years have seen researchers engineer programmed information processing, computation, and control functions in living systems based on RNA devices responsive to diverse molecular inputs. More recently, researchers have assembled RNA-based nanostructures that act as scaffolds to spatially coordinate biochemical reactions inside cells. The integration of programmable spatial organization and dynamic control strategies afforded by RNA-based platforms will allow transformative advances in biological system design. To push the field forward, several challenges must be addressed, including: (i) limitations in the diversity of RNA parts from which to build devices encoding more complex functions, (ii) strategies that support the design of robustly-operating systems from “imperfect” parts, (iii) strategies that support the design of nucleic acid-based computational schemes in cellular environments (i.e., complex and noisy).

Discussion

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