Fascinating World of Molecular Robotics

Image Credit: Wyss Institute

On September 21st 2018, couple hundred people came together in Boston to attend the 9th Annual Wyss International Symposium. The topic of this year was Molecular Robotics. I have to confess that this is not my field of expertise beyond a synthetic biology course, however, coming from a computer science background, most topics were somewhat familiar.

The event booklet describes molecular robotics as: “encompassing the design of microscopic, self-assembly driven agents that sense, compute and actuate”.

Furthermore they state that “Nanoscale robots composed of nucleid acids, proteins or other molecules do not require power or batteries to operate, can be programmed to complete their tasks autonomously and collectively, and offer an unprecedented level of interaction with and control of biological systems”.

Potential application areas are clinical diagnostics and therapeutics. Molecular robotics also extends “robotics” into the “realm of nanoscale molecular systems with large numbers of individual agents collectively accomplishing tasks at microscopic scales”.

Talks were divided into sessions covering the state of the art in sensing, computing and actuating aspects of the field. The final session titled “Translate” aimed to discuss how all this can be translated into applications in real life.

The Wyss Institute just released a recap of the event, which is a must read. Unfortunately, the video recordings of the event are not made public. I scanned the web for other presentations from some of the speakers (disclaimer: these videos are not exactly what was presented at this event)

Sense

William Shih, Harvard Medical School

2013— Dr. Shi is developing self-assembling DNA nanostructures and devices for use in biomedical applications. His group previously solved a key challenge for nanotechnology: programmable self-assembly of complex, three-dimensional nanostructures. Their solution was to build custom three-dimensional structures that can be conceived as stacks of nearly flat layers of DNA. The lecture will discuss applications of this technology for molecular biophysics illustrated by its use to make weak-alignment media for NMR structure determination of membrane proteins; to build 3-D scaffolds for determining the number of “SNARE” complexes necessary to fuse lipid-bilayers, and to study how the shape and size of DNA nanoparticles affects their rates of cellular internalization. The lecture will further discuss applications of the technology for medical therapeutics.

Yamuna Krishnan, University of Chicago

2016 — Yamuna Krishnan -Because of its microscopic size and predictable modular structure, DNA is an ideal building material for nanoscale devices. These DNA-based nanodevices can function as platforms that allow testing of certain features of molecular circuits in carefully controlled settings. Yamuna Krishnan explains how her team creates these nanodevices to target cancer cells in living beings, interpret biochemical signals to report on health and find disease, and more.

Hendrik Dietz, Technical University Munich

2016-Hendrik Dietz is a professor for biophysics at the Technical University Munich (https://www.dietzlab.org/) and is the head of the Laboratory for Biomolecular Nanotechnology there. His lab uses DNA origami to engineer artificial nanodevices, which can execute user-defined tasks. While at the 14th Horizons in Molecular Biology he talked about “Molecular Systems engineering with DNA” introducing key concepts and highlighting the most recent and exciting developments in this field

Compute

Lulu Qian, Caltech

2016 — Lulu Qian, CalTech: “A Future Written by Molecular Programmers” , Assistant Professor of Bioengineering, is interested in engineering molecular systems with intelligent behavior: specifically, exploring the principles of molecular programs in nature with the end goal of recreating synthetic molecular programs that approach the complexity and sophistication of life itself. To this end, she works on designing and constructing nucleic-acid systems from scratch that exhibit programmable behaviors from the basic level — such as recognizing molecular events from the environment, processing information, making decisions, and taking actions — to the advanced level, such as learning and evolving.

George Church, Harvard University

2014-George Church-In his talk “The Future of Human Genomics and Synthetic Biology,” Church discussed the exponentially fast pace of emerging genetic technologies (due in part to his own inventions and advancements in the fields of genetics and synthetic biology) and the application of these technologies to present and future work. Synthetic biology, which includes altering gene sequences and expression of genes in living organisms, relies on existing and emerging technologies to manipulate and reconstruct genes and genomes.
2018-At the inaugural Precision CRISPR Stem Cell Congress, founded in partnership with our Allen Institute for Cell Science, George Church presented on: Genome & Epigenome Engineering in Organs & Organoids

Actuate

Itai Cohen, Cornell

2016-Itai Cohen-In his talk, “Bringing Physics into the Fold,” Itai Cohen described the new design principles he and students at Cornell University are uncovering for determining the shape, mechanics, and transformations of origami structures along with their usefulness in areas as diverse as solar design, architecture, and even fashion.

David Baker, University of Washington

David Baker presents on “The coming of age of de novo protein design” at the 2017 Seattle Cell Science Symposium hosted by the Allen Institute for Cell Science

Khalid Salaita, Emory University

2015-Salaita Lab. Unlike other synthetic DNA-based motors, which use legs to ‘walk’ like tiny robots, ours is the first rolling DNA motor, making it far faster and more robust,” says Khalid Salaita, the Emory University chemist who led the study. “It’s like the biological equivalent of the invention of the wheel for the field of DNA machines

A Bit of the History
Digging a bit deeper into the history of molecular robotics on the internet, it appears that the field started as DNA Nanotechnology (or DNA Nanoengineering). Wikipedia names Dr. Nadrian Seeman of NYU (Dept. of Chemistry) as the founding father of DNA Nanotechnology who laid out the main concepts back in the 80s while it really took off in mid-2000s.

I realized this connection based on Japanese scientist Dr. Satoshi Murata’s 2009 grant proposal titled “Development of Molecular Robotics based on DNA Nanoengineering“.

Furthermore, in this video interview (below), released by the NSF covering the 2010 Nature paper “Molecular robots guided by prescriptive landscapes” by Columbia University researchers, Dr. Milan N. Stojanovic is talking about brief history that led to their paper. And in there he mentions the work of Dr. Seeman of NYU. At that time NSF called molecular robotics as “on the rise”:

The Japanese Government has officially started supporting this field back in 2012. Researchers from Japan published a review of the field at the time in 2013. Later, an initiative in molecular robotics was established at Wyss Institute in 2016.

Dr. Seeman has published an article in Nature Reviews titled “DNA nanotechnology” in 2017. Interestingly, in that article he does not use the term “Molecular Robotics” at all.

I also sensed little bit of “artificial life” flavor in all this. Steven Levy’s “Artificial Life” (1992) and John Holland’s (RIP) “Hidden Order:How Adaptation Builds Complexity” (1995) books come to mind.

Molecular robotics is certainly a field to watch! Maybe this will lead to interesting applications as in the novel Nexus :-) or maybe “artificial or synthetic immune systems”? Or this could be the future of drug design.