Nanotechnology and RNA to Protein

[nobahar]

Hello!

I'm guessing nanotechnology poses many difficulties, especially when using synthetic materials to manufacture complicated machines on such a small scale. I was thinking, therefore, that, if the mechanisms of protein folding are figured out, then mRNA sequences can be designed to produce 'designed' proteins. The manufacture of these tiny machines can be undertaken by ribosomes. Although I guess that is only part of the problem. Designing the protein is the other difficulty.
Nonetheless, is there a role for usurping biological methods for making such small scale 'machines', as proteins often are, in the field of nanotechnology? Designing RNA sequences and using either natural or synthetic ribosomes to construct the desired machine?

Hmmmmm. Interesting?

Nobahar.

 

[Ygggdrasil]

Exploiting the abilities of biological molecules to self-assemble into nano-scale materials is a very exciting area of research that many labs are currently working on.

In the area of proteins, protein folding is very complicated, and while scientists have determined some of the basic principles that dictate protein folding, we are still very far away from being able to design proteins to perform any arbitrary function. That said, there have been a number of successes where scientists have been able to computationally design new protein folds (Kuhlman et al. 2003 Design of a novel globular protein fold with atomic-level accuracy. Science 302:1364-8) and even design new enzymes (Rothlisberger et al. 2008 Kemp elimination catalysts by computational enzyme design. Nature, 453:164-6; Jiang et al. 2008 De novo computational design of retro-aldol enzymes. Science, 319:1387-91). However, these enzymes are still much less efficient than their natural counterparts and they catalyze fairly simple reactions. Much research is still required to figure out how to improve our methods of designing enzymes.

DNA and RNA folding, however, follow much simpler rules than protein folding and researchers have been able to make significant progress in creating arbitrary DNA nanostructures. Researchers have developed a technique called DNA origami that can essentially allow the construction of arbitary 2D (Rothemund. 2006 Folding DNA to create nanoscale shapes and patterns Nature 440:297-302) and 3D shapes (Douglas et al. 2009 Self-assembly of DNA into nanoscale three-dimensional shapes. Nature 459:414-8). There is even freely-available software to help researchers design 3D DNA nanostructures (http://cadnano.org/). Of course, while DNA and RNA are very good tools for fabricating nanostructures, it is much more difficult to make them functional (e.g. to act as catalysts or to act as sensors).

On a larger, more integrated level, researchers have also been able to exploit viruses as self-assembling, self-replicating nanoscale machines for synthesizing new materials (Mao et al. 2004 Virus-Based Genetic Toolkit for the Directed Synthesis of Magnetic and Semiconducting Nanowires. Science 303: 213-5; Lee et al. 2009 Fabricating Genetically Engineered High-Power Lithium Ion Batteries Using Multiple Virus Genes. Science 324: 1051-5).

 

[Ryan_m_b]

Synthetic biology offers huge advances in our ability to manufacture new toys. Two cool things that spring to my mind is the http://scitechstory.com/2010/02/17/code-4-letter-codons/" .

 

[nobahar]

In the area of proteins, protein folding is very complicated, and while scientists have determined some of the basic principles that dictate protein folding, we are still very far away from being able to design proteins to perform any arbitrary function. That said, there have been a number of successes where scientists have been able to computationally design new protein folds

Thanks for the response Ygggdrasil and Ryan. There are some interesting articles there to look through. I think this is an extremely interesting area of biology; although, judging from the articles, it seems to fall more into the realm of Physical chemistry and physics than biology. The Kuhlman article was impenetrable. How much crossdisciplinary knowledge would one be expected to have, out of interest?

 

[Ygggdrasil]

I would say that most areas of biology require some crossdisciplinary knowledge, but this is especially true in the area of synthetic biology. For example, the 2008 papers describing computational design of enzymes were a collaboration between four groups: the Baker lab at the University of Washington, a computational biology group that has developed software for predicting and designing protein structures; the Houk lab at UCLA, a computational chemistry lab that has developed tools for performing quantum mechanical calculations to study catalysts; the Stoddard lab at the University of Washington, a structural biology lab that figures out the 3D structures of proteins using x-ray crystallography; and the Tawfik lab at the Weizmann Institute in Israel, a biochemistry group that studies the evolution of enzymes. The computational methods from the Houk lab were needed to correctly design the active site of the protein so that it can perform the correct reaction, and the computational methods from the Baker lab were needed to optimize the rest of the protein structure to position the active site residues in the correct position. They then turned to the expertise of the Stoddard lab to characterize their designed proteins and determine whether they folded into the correct structure, and then to the expertise of the Tawfik lab to use directed evolution methods to fine tune the activity of the designed enzymes.

Because these types of projects require considerable crossdisciplinary expertise, they are rarely ever undertaken by a single individual or even a single lab (at least until the methods are mature enough that they can be performed by non-experts). It is important, however, that all involved have a strong grounding in all of the different disciplines involved so that everyone can at least "speak in the same language" (which can sometimes be a problem when biologists speak to physicists).

 

[Ryan_m_b]

Because these types of projects require considerable crossdisciplinary expertise, they are rarely ever undertaken by a single individual or even a single lab (at least until the methods are mature enough that they can be performed by non-experts). It is important, however, that all involved have a strong grounding in all of the different disciplines involved so that everyone can at least "speak in the same language" (which can sometimes be a problem when biologists speak to physicists).

Interdisciplinary collaboration is a must for projects in synthetic biology and bionanotechnology. I have some personal experience of this; my undergrad was straight biology and in the life science school all departments were separated by areas of study and all labs separated by specific elements. This meant that a biochemist in the e.coli labs would only ever see a developmental biologist from the d.melanogaster labs if they walked through the buildings front door at the same time. And these are just scientists within life science; material scientists, engineers, physicists etc all had buildings elsewhere.

Obviously this is a fairly standard set up and I never thought too much about it (after all if you needed a physicist you could visit/email and consult one) however in my post graduate the departments were arranged by what their research interest was and packed with staff from every arena. This meant that my department (Surgery and Interventional science) was dedicated towards regenerative medicine approaches to prosthetics and employed biochemists, material scientists, mechanical engineers, polymer scientists etc. This was an eye opener for me as to how different and more comprehensive research could be when everyone has a different background.