How to write and store memory?

=Note=

Our memory circuit have to be as modular as possible to have the wider range of applications possibles.

=Writing DNA=

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.

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:
 * Targetting integrase to specific sites

=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

Rewiring cell signalling

Role of modular interaction in the volution and wiring of cell signalling circuits

Engineering synthetic signaling proteins with ultrasensitive input/output control.

reprogramming control of an allosteric signaling switch through modular recombination.

Thus, using specific network motifs, we could write and store memory on this way with great dynamics.

memory storage using fluorescent proteins12

=RNAs=

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


 * Aptamers

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.

aptamers on wikipedia the aptamer database

RNAs that catalyse a chemical reaction link
 * Ribozymes


 * Ribonucleoproteins


 * siRNA/shRNA

=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...