Programming chemistry in DNA-addressable bioreactors

Abstract

We present a formal calculus, termed the chemtainer calculus, able to capture the complexity of compartmentalized reaction systems such as populations of possibly nested vesicular compartments. Compartments contain molecular cargo as well as surface markers in the form of DNA single strands. These markers serve as compartment addresses and allow for their targeted transport and fusion, thereby enabling reactions of previously separated chemicals. The overall system organization allows for the set-up of programmable chemistry in microfluidic or other automated environments. We introduce a simple sequential programming language whose instructions are motivated by stateof-the-art microfluidic technology. Our approach integrates electronic control, chemical computing and material production in a unified formal framework that is able to mimic the integrated computational and constructive capabilities of the subcellular matrix. We provide a non-deterministic semantics of our programming language that enables us to analytically derive the computational and constructive power of our machinery. This semantics is used to derive the sets of all constructable chemicals and supermolecular structures that emerge from different underlying instruction sets. Because our proofs are constructive, they can be used to automatically infer control programs for the construction of target structures from a limited set of resource molecules. Finally, we present an example of our framework from the area of oligosaccharide synthesis.

Formalizing Modularization and Data Hiding in Synthetic Biology

“…We believe, however, that the true potential of the presented methods lies in enabling algorithms and software tools for the computer assisted design of complex synthetic biological designs de novo. In fact, Reller [60], Weyland et al [83] and Fellermann and Cardelli [24] developed algorithms for the automated inference of chemical synthesis pathways in programmable nano-bioreactors.…”

“…Here, we restrict ourselves to the elements of the calculus used in the applications that follow. For a concise exposition, the reader is referred to Fellermann and Cardelli [24].…”

“…The two main branches that concern themselves with compartmentalized reaction systems are P systems, proposed by Paun [57], and brane calculi, proposed by Cardelli [13]. Recently, Fellermann and Cardelli [24] have developed the…”

“…Fellermann and Cardelli [24] and Weyland et al [83] have employed the chemtainer calculus for the programmed synthesis of oligosaccharides -a computational problem first introduced by Reller [60]. Oligosaccharides are branched heteropolymers composed of typically five to ten individual sugar monomers such as mannose, galactose, and glucose.…”

Analysis and design of molecular machines

“…Additionally, the advent of high throughput data in medicine requires computational techniques for data mining. Biologically inspired computation has been used to infer mathematical models, parameter values, or to capture states and transitions at the molecular level [1].…”