Computing with cells: membrane systems - some complexity issues.

Membrane computing is a branch of natural computing which abstracts computing models from the structure and the functioning of the living cell. The main ingredients of membrane systems, called P systems, are (i) the membrane structure, which consists of a hierarchical arrangements of membranes which delimit compartments where (ii) multisets of symbols, called objects, evolve according to (iii) sets of rules which are localised and associated with compartments. By using the rules in a nondeterministic/deterministic maximally parallel manner, transitions between the system configurations can be obtained. A sequence of transitions is a computation of how the system is evolving. Various ways of controlling the transfer of objects from one membrane to another and applying the rules, as well as possibilities to dissolve, divide or create membranes have been studied. Membrane systems have a great potential for implementing massively concurrent systems in an efficient way that would allow us to solve currently intractable problems once future biotechnology gives way to a practical bio-realization. In this paper we survey some interesting and fundamental complexity issues such as universality vs. nonuniversality, determinism vs. nondeterminism, membrane and alphabet size hierarchies, characterizations of context-sensitive languages and other language classes and various notions of parallelism

Remnants of an ancient metabolism without phosphate

Phosphate is essential for all living systems, serving as a building block of genetic and metabolic machinery. However, it is unclear how phosphate could have assumed these central roles on primordial Earth, given its poor geochemical accessibility. We used systems biology approaches to explore the alternative hypothesis that a protometabolism could have emerged prior to the incorporation of phosphate. Surprisingly, we identified a cryptic phosphate-independent core metabolism producible from simple prebiotic compounds. This network is predicted to support the biosynthesis of a broad category of key biomolecules. Its enrichment for enzymes utilizing iron-sulfur clusters, and the fact that thermodynamic bottlenecks are more readily overcome by thioester rather than phosphate couplings, suggest that this network may constitute a "metabolic fossil" of an early phosphate-free nonenzymatic biochemistry. Our results corroborate and expand previous proposals that a putative thioester-based metabolism could have predated the incorporation of phosphate and an RNA-based genetic system. PAPERCLIP

Environmental boundary conditions for the origin of life converge to an organo-sulfur metabolism

Published in final edited form as: Nat Ecol Evol. 2019 December ; 3(12): 1715–1724. doi:10.1038/s41559-019-1018-8.It has been suggested that a deep memory of early life is hidden in the architecture of metabolic networks, whose reactions could have been catalyzed by small molecules or minerals before genetically encoded enzymes. A major challenge in unravelling these early steps is assessing the plausibility of a connected, thermodynamically consistent proto-metabolism under different geochemical conditions, which are still surrounded by high uncertainty. Here we combine network-based algorithms with physico-chemical constraints on chemical reaction networks to systematically show how different combinations of parameters (temperature, pH, redox potential and availability of molecular precursors) could have affected the evolution of a proto-metabolism. Our analysis of possible trajectories indicates that a subset of boundary conditions converges to an organo-sulfur-based proto-metabolic network fuelled by a thioester- and redox-driven variant of the reductive tricarboxylic acid cycle that is capable of producing lipids and keto acids. Surprisingly, environmental sources of fixed nitrogen and low-potential electron donors are not necessary for the earliest phases of biochemical evolution. We use one of these networks to build a steady-state dynamical metabolic model of a protocell, and find that different combinations of carbon sources and electron donors can support the continuous production of a minimal ancient 'biomass' composed of putative early biopolymers and fatty acids.80NSSC17K0295 - Intramural NASA; 80NSSC17K0296 - Intramural NASA; T32 GM100842 - NIGMS NIH HHSAccepted manuscrip

The compositional and evolutionary logic of metabolism

Metabolism displays striking and robust regularities in the forms of modularity and hierarchy, whose composition may be compactly described. This renders metabolic architecture comprehensible as a system, and suggests the order in which layers of that system emerged. Metabolism also serves as the foundation in other hierarchies, at least up to cellular integration including bioenergetics and molecular replication, and trophic ecology. The recapitulation of patterns first seen in metabolism, in these higher levels, suggests metabolism as a source of causation or constraint on many forms of organization in the biosphere. We identify as modules widely reused subsets of chemicals, reactions, or functions, each with a conserved internal structure. At the small molecule substrate level, module boundaries are generally associated with the most complex reaction mechanisms and the most conserved enzymes. Cofactors form a structurally and functionally distinctive control layer over the small-molecule substrate. Complex cofactors are often used at module boundaries of the substrate level, while simpler ones participate in widely used reactions. Cofactor functions thus act as "keys" that incorporate classes of organic reactions within biochemistry. The same modules that organize the compositional diversity of metabolism are argued to have governed long-term evolution. Early evolution of core metabolism, especially carbon-fixation, appears to have required few innovations among a small number of conserved modules, to produce adaptations to simple biogeochemical changes of environment. We demonstrate these features of metabolism at several levels of hierarchy, beginning with the small-molecule substrate and network architecture, continuing with cofactors and key conserved reactions, and culminating in the aggregation of multiple diverse physical and biochemical processes in cells.Comment: 56 pages, 28 figure

Programmability of Chemical Reaction Networks

Motivated by the intriguing complexity of biochemical circuitry within individual cells we study Stochastic Chemical Reaction Networks (SCRNs), a formal model that considers a set of chemical reactions acting on a finite number of molecules in a well-stirred solution according to standard chemical kinetics equations. SCRNs have been widely used for describing naturally occurring (bio)chemical systems, and with the advent of synthetic biology they become a promising language for the design of artificial biochemical circuits. Our interest here is the computational power of SCRNs and how they relate to more conventional models of computation. We survey known connections and give new connections between SCRNs and Boolean Logic Circuits, Vector Addition Systems, Petri Nets, Gate Implementability, Primitive Recursive Functions, Register Machines, Fractran, and Turing Machines. A theme to these investigations is the thin line between decidable and undecidable questions about SCRN behavior

Proceedings of the Workshop on Membrane Computing, WMC 2016.

yesThis Workshop on Membrane Computing, at the Conference of Unconventional Computation and Natural Computation (UCNC), 12th July 2016, Manchester, UK, is the second event of this type after the Workshop at UCNC 2015 in Auckland, New Zealand*. Following the tradition of the 2015 Workshop the Proceedings are published as technical report. The Workshop consisted of one invited talk and six contributed presentations (three full papers and three extended abstracts) covering a broad spectrum of topics in Membrane Computing, from computational and complexity theory to formal verification, simulation and applications in robotics. All these papers – see below, but the last extended abstract, are included in this volume. The invited talk given by Rudolf Freund, “P SystemsWorking in Set Modes”, presented a general overview on basic topics in the theory of Membrane Computing as well as new developments and future research directions in this area. Radu Nicolescu in “Distributed and Parallel Dynamic Programming Algorithms Modelled on cP Systems” presented an interesting dynamic programming algorithm in a distributed and parallel setting based on P systems enriched with adequate data structure and programming concepts representation. Omar Belingheri, Antonio E. Porreca and Claudio Zandron showed in “P Systems with Hybrid Sets” that P systems with negative multiplicities of objects are less powerful than Turing machines. Artiom Alhazov, Rudolf Freund and Sergiu Ivanov presented in “Extended Spiking Neural P Systems with States” new results regading the newly introduced topic of spiking neural P systems where states are considered. “Selection Criteria for Statistical Model Checker”, by Mehmet E. Bakir and Mike Stannett, presented some early experiments in selecting adequate statistical model checkers for biological systems modelled with P systems. In “Towards Agent-Based Simulation of Kernel P Systems using FLAME and FLAME GPU”, Raluca Lefticaru, Luis F. Macías-Ramos, Ionuţ M. Niculescu, Laurenţiu Mierlă presented some of the advatages of implementing kernel P systems simulations in FLAME. Andrei G. Florea and Cătălin Buiu, in “An Efficient Implementation and Integration of a P Colony Simulator for Swarm Robotics Applications" presented an interesting and efficient implementation based on P colonies for swarms of Kilobot robots. *http://ucnc15.wordpress.fos.auckland.ac.nz/workshop-on-membrane-computingwmc- at-the-conference-on-unconventional-computation-natural-computation

Further Open Problems in Membrane Computing

A series of open problems and research topics in membrane com- puting are pointed out, most of them suggested by recent developments in this area. Many of these problems have several facets and branchings, and further facets and branchings can surely be found after addressing them in a more careful manner

Communication in membrana Systems with symbol Objects.

Esta tesis está dedicada a los sistemas de membranas con objetos-símbolo como marco teórico de los sistemas paralelos y distribuidos de procesamiento de multiconjuntos.Una computación de parada puede aceptar, generar o procesar un número, un vector o una palabra; por tanto el sistema define globalmente (a través de los resultados de todas sus computaciones) un conjunto de números, de vectores, de palabras (es decir, un lenguaje), o bien una función. En esta tesis estudiamos la capacidad de estos sistemas para resolver problemas particulares, así como su potencia computacional. Por ejemplo, las familias de lenguajes definidas por diversas clases de estos sistemas se comparan con las familias clásicas, esto es, lenguajes regulares, independientes del contexto, generados por sistemas 0L tabulados extendidos, generados por gramáticas matriciales sin chequeo de apariciones, recursivamente enumerables, etc. Se prestará especial atención a la comunicación de objetos entre regiones y a las distintas formas de cooperación entre ellos.Se pretende (Sección 3.4) realizar una formalización los sistemas de membranas y construir una herramienta tipo software para la variante que usa cooperación no distribuida, el navegador de configuraciones, es decir, un simulador, en el cual el usuario selecciona la siguiente configuración entre todas las posibles, estando permitido volver hacia atrás. Se considerarán diversos modelos distribuidos. En el modelo de evolución y comunicación (Capítulo 4) separamos las reglas tipo-reescritura y las reglas de transporte (llamadas symport y antiport). Los sistemas de bombeo de protones (proton pumping, Secciones 4.8, 4.9) constituyen una variante de los sistemas de evolución y comunicación con un modo restrictivo de cooperación. Un modelo especial de computación con membranas es el modelo puramente comunicativo, en el cual los objetos traspasan juntos una membrana. Estudiamos la potencia computacional de las sistemas de membranas con symport/antiport de 2 o 3 objetos (Capítulo 5) y la potencia computacional de las sistemas de membranas con alfabeto limitado (Capítulo 6).El determinismo (Secciones 4.7, 5.5, etc.) es una característica especial (restrictiva) de los sistemas computacionales. Se pondrá especial énfasis en analizar si esta restricción reduce o no la potencia computacional de los mismos. Los resultados obtenidos para sistemas de bombeo del protones están transferidos (Sección 7.3) a sistemas con catalizadores bistabiles. Unos ejemplos de aplicación concreta de los sistemas de membranas (Secciones 7.1, 7.2) son la resolución de problemas NP-completos en tiempo polinomial y la resolución de problemas de ordenación.This thesis deals with membrane systems with symbol objects as a theoretical framework of distributed parallel multiset processing systems.A halting computation can accept, generate or process a number, a vector or a word, so the system globally defines (by the results of all its computations) a set of numbers or a set of vectors or a set of words, (i.e., a language), or a function. The ability of these systems to solve particular problems is investigated, as well as their computational power, e.g., the language families defined by different classes of these systems are compared to the classical ones, i.e., regular, context-free, languages generated by extended tabled 0L systems, languages generated by matrix grammars without appearance checking, recursively enumerable languages, etc. Special attention is paid to communication of objects between the regions and to the ways of cooperation between the objects.An attempt to formalize the membrane systems is made (Section 3.4), and a software tool is constructed for the non-distributed cooperative variant, the configuration browser, i.e., a simulator, where the user chooses the next configuration among the possible ones and can go back. Different distributed models are considered. In the evolution-communication model (Chapter 4) rewriting-like rules are separated from transport rules. Proton pumping systems (Sections 4.8, 4.9) are a variant of the evolution-communication systems with a restricted way of cooperation. A special membrane computing model is a purely communicative one: the objects are moved together through a membrane. We study the computational power of membrane systems with symport/antiport of 2 or 3 objects (Chapter 5) and the computational power of membrane systems with a limited alphabet (Chapter 6).Determinism (Sections 4.7, 5.5, etc.) is a special property of computational systems; the question of whether this restriction reduces the computational power is addressed. The results on proton pumping systems can be carried over (Section 7.3) to the systems with bi-stable catalysts. Some particular examples of membrane systems applications are solving NP-complete problems in polynomial time, and solving the sorting problem