Synthetic Cellular Memory

Introduction

Synthetic cellular memory refers to the engineering of living organisms to produce a "protracted response to a transient stimulus" (Gardner, 2000 and Ajo-Franklin, 2007). Research in this area thus far has produced simple genetic circuits that change a cell's phenotype in response to a change in environment. In the short term, construction of such gene networks provides a more thorough understanding of natural systems. By matching experimental results with mathematical models, we can put our knowledge of systems biology to the test. In the long run, cellular memory promises to be a key component of synthetic biological design. While current research efforts have been directed at the production of a reporter protein in response to some input, memory circuits hold the potential to be incorporated into more complex gene networks. Engineered cell differentiation, detection of hazardous materials in drinking water, biocomputing, gene therapy, and other such applications of synthetic devices could all one day depend on modular memory circuits similar to the ones described in this paper (Gardner, 2000 and Ajo-Franklin, 2007).

Description of Wiki-Paper Contents

In order to examine the current state of the field of synthetic cellular memory, I will first look at common biological designs that are used to construct simple memory circuits in vivo. Memory circuits typically fall into one of two categories: mutual repression and autoregulatory positive feedback. Each of these networks will be described in detail. I will then present a few different mathematical models that are used to describe how these biological circuits function.

From there, three different papers will be discussed in detail:

The first paper describes the construction of a genetic toggle switch in E. coli (Gardner, 2000). Published in 2000, this was a groundbreaking paper that laid the foundation for much of the research that has since been done on synthetic gene networks. While the genetic toggle switch is one of the most simplistic forms of synthetic memory, the establishment of a predictive mathematical model and a functional biological device set the stage for more complex networks to be constructed in more complex organisms.

The second paper was published five years later and discusses the construction of a hysteretic memory switch in mammalian cells (Kramer, 2005). This circuit improves upon the bistable toggle switch by adjusting the toggle-point based on the history of the cell. This work also demonstrates the feasibility of incorporating synthetic cellular memory into eukaryotic cells.

The final paper, published in September of 2007, details a "permanent" memory network in yeast cells (Ajo-Franklin, 2007). Yeast were engineered to fluoresce indefinitely after sensing an input. This system is a move towards non-rewritable synthetic cellular memory. After the cells have sensed an input, their "memory" state is retained in all environments (as opposed to toggling back and forth between two different states), even through multiple cell divisions. An accurate mathematical model was also developed to predict network behavior in this eukaryotic system based on quantitative part characterization.

After discussion of these three papers, the contents of this wiki-paper will be summarized and future directions of the field will be analyzed.