Cells as Machines: Towards Deciphering Biochemical Programs in the Cell

Abstract

Abstract. Systems biology aims at understanding complex biological processes in terms of their basic mechanisms at the molecular level in cells. The bet of applying theoretical computer science concepts and software engineering methods to the analysis of distributed biochemical reaction systems in the cell, designed by natural evolution, has led to interesting challenges in computer science, and new model-based insights in biology. In this paper, we review the development over the last decade of the biochemical abstract machine (Biocham) software environment for modeling cell biology molecular reaction systems, reasoning about them at different levels of abstraction, formalizing biological behaviors in temporal logic with numerical constraints, and using them to infer non-measurable kinetic parameter values, evaluate robustness, decipher natural biochemical processes and implement new programs in synthetic biology.

A Survey on Analog Models of Computation

“…Areas such as systems biology aim at understanding complex biological processes in terms of their basic mechanisms at the molecular level. Many attempts of applying concepts and tools from theoretical computer science to this framework (logic, algebra, etc..) have been investigated, with numerous successes and concrete software systems: see [165].…”

“…A context where various semantics have been discussed, with clear stated vocabulary, is that of chemical reactions. To a given formal set of chemical reactions, a hierarchy of semantics can be associated at different levels of abstraction [165].…”

“…The very classical algorithm of Gillespie [182] provides a method to simulate efficiently this CTMC from the reactions. If the simulation provided by this algorithm is often similar to the ODE simulation for large number of molecules, it may exhibit qualitatively different behaviors, in particular when the number of molecules is small [165].…”

Whole cell biosynthetic activity of Komagataella phaffii (Pichia pastoris) GS115 strains engineered with transgenes encoding Chromobacterium violaceum ω‐transaminase alone or combined with native transketolase

“…Whole cell biocatalysis enables the design of self‐renewing, multienzyme micromachines capable of dynamically maintaining controlled internal environments sequestered from exterior conditions. These three key features define the utility of whole cell biocatalysis for use with low value or crude feedstocks and for production of complex products.…”