Tuesday, February 17, 2009

Borrowing sub-systems from another orgnanism

Engineering a cell is mostly done at the genetic level because that is where the tools are available. However, it is possible to borrow an entire system from another organism, such that the controls of the system are at the genetic level. 

Consider a system with various proteins, including a few transcription factors. Now, lets take the system as a whole and consider the fact that we can control the concentrations of each of the members of the system, and we can take as "output" the concentrations of all the transcription factors in the system. As long as the entire system does not interact with the host machinery, this can be a generic strategy for borrowing systems, rather than genes, from other organisms. 

Sunday, February 15, 2009

Borrowing phosphorylation cycle from another organism

Perhaps it is not neccessary to engineer proteins themselved in order to engineer a cell at the protein level. 

Suppose organism Y has a system composed of a kinase, phosphatase, and transcription factor(s) that is controlled via phosphorylation. This entire system can be transplanted into organism X (e.g. E. coli), with each component under the control of different promoters. 

This will give some control at the protein level, because the equilibrium concentrations of the phosphorylated and unphosphorylated proteins can be controlled by regulating the levels of the kinase and phosphotase. Of course, the control is still at the transcription level, but the phosphorylation will serve as a fast-acting system -- i.e. producing a few kinases will activate many transcription factors. 

Saturday, February 14, 2009

Feed forwards

Apparently, the dynamical system involving only feed forward neural networks (not artificial) converge to a single point. Feedback is required in order to create complex effects, such as convergence to a complex attractors, etc. The structure of genetic networks is similar, and E. coli's regulatory network is largely composed of feed forward networks and very little feedback (except self-loops). Is it possible that for a single input pattern, the cell is adapted to respond in the same way every time, somewhat like a neural network learning an input pattern? 

Is it possible that the genetic network "sets up" the community of proteins in the cell. The community of proteins determine the dynamics of the cell. In this is the case, then the genetic network is a system that takes input from the environment and produces a dynamical system, or  machine, as the output. The dynamical system is designed to survive in the particular input environment. Here is an somewhat odd example (completely hypothetical) :

Lets consider a Venus fly trap or some similar plant...

input: bug lands inside the plant's mouth.
processing: some transcription factor triggered
output: production of several insect digestion enzymes

The output proteins may not just be for digestion itself. They might together form a small machine, such as an oscillator that is responsible for closing the mouth, or some other mechanics that is responsible for carrying out the whole digestion process. By identifying the machine that is the "output" it may be possible to learn behavior pattern is needed to cope to particular environmental signals. 

Tuesday, February 10, 2009

Using broken transcription factors as AND logic

Yeast-2-Hybrid is a technique where gene X is placed under the control of a transcription factor TF, but TF will only become active when proteins A and B interact with each other. This same concept can use used to create a transcriptional AND gate:

gene A --> protein A
gene B --> protein B

TF is only active when proteins A and B are present. Hence, gene X =  gene A && gene B