How to write and store memory?
Our memory circuit have to be as modular as possible to have the wider range of applications possibles.
Changes in DNA sequence could control expression of proteins ARNs to store and read the state. see Ton's presentation on DNA writers. Advantage of DNA is its extreme stability, the lot of modifying enzymes available, their high precision, and the high modularity of regulatory elements.
- Targetting integrase to specific sites
By fusionning HIV integrase, which integrates in a non-specific fashion, to DNA binding domains, it is possible to direct integration to specific DNA sequences. However, if integration seems to occur in the desired region, the process seems currently to lack precision. References:
Synthetic proteins signaling pathways
Advantage of using proteins networks is their extreme dynamical response compared to transcriptionnal networks. The main difficulty is that if modularity is also a feature of proteins, context dependent effects are greater than with DNA and not yet fully understood. However, modularity is quite developed in eukaryotic proteins, with a lot of proteins domains available, and pioneering work from Wendell Lim's lab has shown that it is possible to built artificial proteins proteins pathways. This should thus be an issue to be considered. Reversible post-tranlationnal modification for example phosphorylations: Kinase are "writer", phosphatases "eraser" and domains that bind (like SH2 domain) the "readers" (from Pincus et al., 2008)
Synthetic scaffold: Link
Thus, using specific network motifs, we could write and store memory on this way with great dynamics.
RNAs are a highlly versatile and potent tool to engineer.With more functions than DNA and more predictable than proteins... Recently, systems capable of information processing using RNA has been engineered with success:Win and Smolke, 2008
Smal RNA molecules selected from library to bind virtually any kind of molecules, kind of a "RNA-antibody". The candidate is then optimized by multiple iterations (in vitro evolution or Selex.
RNAs that catalyse a chemical reaction link
Idées en vrac
One can also combine all these mechanisms. for example, a protein could be sequestered on DNA by fusion with a DNA binding protein. signal could activate alteration of the binding sequence (mutation, dsb) and release the protein...integration of the binding sequence could reverse the process....
Signalling circuits composed of RNA and proteins, RNA that bind and activate/inactivate proteins for example...