Wednesday, December 14, 2005

21st Century Lego: Synthetic Biology and Molecular Engineering

As long as I can remember, I've always enjoyed designing and building stuff. I have clear memories of building things with tinkertoy when I was around 3 years old, and as I grew up I made the usual progression through Lego, mechano, balsa wood models, electronics, software, ... The stuff you can build is limited only by the properties of the building materials, your skill level and knowledge, and your imagination. Well, wouldn't it be cool if you could build stuff out of molecules? If, through synthetic biology, you could craft some DNA to create the necessary infrastructure within a cell to create a tiny manufacturing plant for, say, carbon nanotubes?

First thing to do when some far out idea like this pops into your head is to see if someone else has thought of it too (which is almost always the case).

As we become more adept at modifying proteins not just for binding but for catalysis, the nanotechnologist can begin to glimpse some rather dizzying prospects. Can one design an enzyme that constructs carbon nanotubes [39], perhaps even with a specified diameter and chirality (and hence electronic structure)? Could such a molecule then be fitted with a recognition tag that will ensure it does its job of construction only at a particular location in a semiconductor landscape?

Natural proteins and protein-based assemblies have shown considerable potential for nanotechnological applications. The light-activated proton pump bacteriorhodopsin, a membrane protein that regulates the pH of some bacterial cells, is perhaps the prototype, having been used over 10 years ago as a material for optical molecular data storage [40].

More recently, Meier et al [41] have shown that this and other membrane proteins will retain their structure and function when immobilized in thin, robust films of
crosslinked copolymers with a hydrophilic–hydrophobic–hydrophilic sandwich structure, mimicking the environment of lipid membranes. Ho et al [42] used bacteriorhodopsin immobilized in such a polymer membrane to actively pump protons against a pH gradient and thereby to reduce hydrogen ion leakage across the proton exchange membrane of a fuel cell.
More ambitiously, can we imagine designing a cell that will build a genuine photovoltaic cell based on the chloroplast, or a versatile and programmable polymer synthesis factory based on the ribosome?
It is not at all hard to envisage bacteria or viruses acting as sensor devices that detect and signal (by fluorescence, say) traces of certain substances in their environment. More startling, perhaps, are possibilities such as programming cells to reproduce the algorithms of cellular automata—an ironic reversal of the metaphor—so that they interact with their neighbours in tightly prescribed ways, allowing them to develop spontaneous patterns, collective and multicelled behaviour, and even forms of computing

NASA Ames Research Lab
from :

Ames is focusing on a major component of all cells (proteins) that are capable of self-assembling into highly ordered structures. A protein known as HSP60, which spontaneously forms nano-scale ring structures that can be induced to form chains or filaments is currently being studied.

ring structures (fig. 1a, end view; 1b, side view), chains (fig. 1c),filaments (fig. 1d)

With thermostable HSP60s, highly efficient methods have been developed for purifying large quantities of these proteins; their composition and structure-forming capabilities are being currently modified by using the "tools" of molecular biology. For example, if a small fragment of the HSP60 protein is removed, protein rings are produced that do not form chains or filaments, but continue to form rings that spontaneously assemble into highly ordered hexagonally packed arrays. If these proteins are modified to bind metal atoms, they can be used as a template to create an ordered pattern of metal on a surface with nanometer spacing. Ultimately the hope is to use such ordered arrays of metal to manufacture nano-scale electronic devices. Similarly, metal binding to proteins that form filaments may be used to create self-assembling nano-scale wires, which may someday be used to produce self-assembling circuits.

Modified proteins form hexagonally packed rings (left) or metal-containing protein filaments (right)

MIT's Biobricks

from : A registry of 'standard biological parts' aka bio-bricks:


There are currently about 300 BioBricks, and another 800 parts have been built by combining those into composite BioBricks. Knight and his collaborators presented results on a next generation of the system called BioBricks++.

Just as object-oriented programming constructs allowed programmers to quickly combine previous software modules into more complex systems, the BioBricks++ system has standard interfaces for all DNA segments that can be combined in any sequence using commercially available enzymes.

Rettberg is working on an online data book, and is initiating a standards process so that anyone can build BioBricks and add them to the catalog. He envisions an assembly service with measurement and quality control leading to the evolution of "open source biology". Rettberg is also organizing a summer design contest sponsored by the National Science Foundation and the Defense Advanced Research Projects Agency, where teams of graduate and undergraduate students will genetically engineer a Finite State Machine


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