Monday, November 11, 2013

Nanobots: Using nature to beat nature

Emulating nature.. yet again!

Inspired by the melanophore cell, which controls color in fish, scientists at Oxford University and Warwick University* have developed self-assembling transport networks powered by motors controlled by DNA -- the genetic instructions found in nearly all known life.

The system constructs its own network of tracks spanning tens of micrometers in length -- less than the thickness of a sheet of paper -- and then it transports cargo across the network, and even dismantles the tracks.

How the system works

The system is modeled after melanophore cells, which work by controlling the location of pigment in them. The structure of the cell is a network of spokes like a bicycle wheel, and it works by having motor proteins transport pigment in the network, either concentrating it in the central hub or spreading it throughout the network. Concentrating pigment in the center makes the cells lighter as the surrounding space is left empty and transparent.

The system developed by the Oxford University team is similar, and is built from DNA and a motor protein known as kinesin. Powered by ATP fuel -- the smallest unit of energy transport -- kinesins move along the micro-tracks carrying RNA control-modules made from short stands of DNA. 

"DNA is an excellent building block for constructing synthetic molecular systems, as we can program it to do whatever we need," said Adam Wollman, who conducted the research at Oxford University's Department of Physics. "We design the chemical structures of the DNA strands to control how they interact with each other. The shuttles can be used to either carry cargo or deliver signals to tell other shuttles what to do."

Wollman added, "We first use assemblers to arrange the track into 'spokes', triggered by the introduction of ATP. We then send in shuttles with fluorescent green cargo which spread out across the track, covering it evenly. When we add more ATP, the shuttles all cluster in the centre of the track where the spokes meet. Next, we send signal shuttles along the tracks to tell the cargo-carrying shuttles to release the fluorescent cargo into the environment, where it disperses. We can also send shuttles programmed with 'dismantle' signals to the central hub, telling the tracks to break up."

How else could this system be used to cure disease?

This demonstration used fluorescent green dyes as cargo, but the same methods could be applied to other molecules, like life-saving ones!

More broadly, using DNA to control motor proteins will enable the development of more sophisticated self-assembling systems for a wide variety of applications.

Many diseases are prime targets. Some diseases are a result of a overproduction or underproduction of a molecule within certain cells. So that means that these diseases can be "solved" by adjusting the amount of that problematic molecule in those cells.

Take for example the autoimmune disease known as Wegener's granulomatosis. It's an autoimmune disease affecting blood vessels where a certain class of molecules known as reactive oxygen intermediate molecules are overproduced. The job of these molecules is to destroy foreign particles like harmful bacteria, but if the molecule is overproduced, then it begins to indiscriminately destroy the body that it's supposed to be protecting.

So imagine a nanobot system that measures and then adjusts the amount of that problematic molecule within the cells that produce it, namely macrophages and neutrophils.

The same system can "solve" rheumatoid arthritis, which is basically the same autoimmune disease where reactive oxygen intermediate molecules and other toxic molecules are made by overproductive macrophages and neutrophils invading the joints. The toxic molecules contribute to inflammation, which is observed as warmth and swelling, and participate in damage to the joint.

And by controlling the amount of these problematic molecules within the macrophages and neutrophils, we can effectively control the level of that molecule so that it doesn't destroy what your immune system is supposed to be protecting, your body's tissue.


Such a system might even be able to "solve" HIV/AIDS. The HIV virus works like a trojan horse, getting itself into T-cells, a type of macrophage, and then basically "tricking" the cells to create a copy of DNA from the virus' RNA, and then to copy that foreign DNA into one of it's own 46 chromosomes, resulting in turning that cell into a "brainwashed" traitor. The traitor cell then produces the virus until it erupts and then those new viruses go repeat the same thing to other T-cells. This happens until there are so few T-cells that the person's immune system is debilitated to the point of not even being able to defend against the common cold.

Now, what we've recently learned about why some people have the HIV virus, but live for decades without much trouble, is that there are two immune responses to the HIV viral invasion, one of which is effective at stopping the virus while the other isn't so much. So if we discovered the biochemical process that causes the more effective response, and if we controlled the molecules of that process, or the molecules that initiate that process, then we could effectively make a person's T-cells fight the virus better. And that's something a nanobot system could possibly do in the near future.


Such a system might even be able to help with cancer, and I mean all types. Cancer is a type of disease where a certain part of a cell's genetic code gets damaged and doesn't get repaired -- the part that is responsible for cell division. When cell division is working properly, the cell goes through its normal life cycle and then divides to make two cells when it's ready. But, when that part of the process stops working properly, let's say because the genes responsible for that process have mutated, then the cell divides erratically, and then the resulting new cells have the same mutation resulting in more erratically-dividing cells that no longer fill the function they are supposed to. 

Now, cells have a natural defense against mutations in general. They repair DNA constantly, which is necessary because mutations occur so frequently -- about 1 million times per cell per day. Now sometimes these mutations don't get fixed, which is what makes it possible for new genes to enter the gene pool, which is what makes genetic evolution possible. Most mutations turn out to be harmless, but sometimes they aren't. The ones that occur in the genes that control cell-division, are among the bad ones, because they can cause cancer.

Fortunately there is another failsafe system to help catch these types of mistakes. What this system does is to initiate the cell's self-destruct mechanism, also known as apoptosis. Unfortunately, even this system doesn't catch all the mistakes, and it's these cases that result in cancer.

The potential here is in the DNA repair system. In order to help stave off cancer, the rate of DNA repair needs to be more than the rate of mutations. The normal situation is where mutations occur and where they are also being corrected faster than they are occurring. The correcting mechanism is there as a defense against too many mutations, so if the correcting mechanism isn't keeping up with the rate of mutations, then it's only a matter of time before cells become cancerous.** This is why physicians suggest that people limit themselves from activities that increase the rate of mutations, like sunbathing and smoking cigarettes. But another way would be to increase the rate of the DNA repair by adjusting the precursor molecules that drive that mechanism, effectively allowing the rate of genetic corrections to beat the rate of mutations, thus helping to prevent cancer before it even starts. And that's something a nanobot system could possibly do in the near future.

There's so much potential here. Just imagine how many more lives would be saved! And imagine the cost savings.

One day these diseases will exist only as pictures and stories in history books and museums. 

Using nature to beat nature! That's the power of ideas! That's the power of the human mind!


* The work is published in Nature Nanotechnology and was supported by the Engineering and Physical Sciences Research Council and the Biotechnology and Biological Sciences Research Council.

** Browner, WS; Kahn, AJ; Ziv, E; Reiner, AP; Oshima, J; Cawthon, RM; Hsueh, WC; Cummings, SR. (2004). "The genetics of human longevity". Am J Med 117 (11): 851–60.doi:10.1016/j.amjmed.2004.06.033. PMID 15589490.

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