Technology Modelling and Technology Innovation

Working Paper Ircres-CNR 03/2016. This work concerns an extension of a mathematical model of technology developed at the Santa Fe Institute in the late nineties. It is based on analogies existing between technological and biological evolution and not on economic principles. This extension has the purpose to make the model useful in the studies of the innovation process. The model considers technology activity, independently of possible economic purposes, and having its own properties, structure, processes as well as an evolution independently by economic factors but more similar to biologic evolution. Considered purpose of technology is reaching of a technical result and not necessarily an economic result. The model considers technology as a structured set of technological operations that may be represented by a graph or matrix. That opens a description of a technology in term of technological spaces and landscapes, as well as in term of spaces of technologies, in which it is possible to represent search of optimal and evolutive paths of technologies, changes in their efficiency and measure of their radical degree linked to their technological competitiveness. The model is presented in a descriptive way and its mathematical development is presented in annex. The main applications of the model concern the use of the defined radical degree of a technology linked to its technological competitiveness. In this way it is explained the existence of Red Queen Regimes, characterized by continuous technical but not economical developments, among firms producing the same product. Such regimes are disrupted only by the entering of a technology with a high radical degree. Changes in operational structure of technologies may suggest the existence of three types of technology innovations, the first concerning learning by doing and consisting in minor changes giving incremental innovations, the second and the third, both able to obtain radical innovations through R&D activity, but the second exploiting scientific results and the third based only on a combinatory process of pre-existing technologies. This last way of innovation may explain the innovative potential, existing for example in Italian industrial districts, without resorting to any scientific research. 

Mapping the Environmental Fitness Landscape of a Synthetic Gene Circuit

Gene expression actualizes the organismal phenotypes encoded within the genome in an environment-dependent manner. Among all encoded phenotypes, cell population growth rate (fitness) is perhaps the most important, since it determines how well-adapted a genotype is in various environments. Traditional biological measurement techniques have revealed the connection between the environment and fitness based on the gene expression mean. Yet, recently it became clear that cells with identical genomes exposed to the same environment can differ dramatically from the population average in their gene expression and division rate (individual fitness). For cell populations with bimodal gene expression, this difference is particularly pronounced, and may involve stochastic transitions between two cellular states that form distinct sub-populations. Currently it remains unclear how a cell population's growth rate and its subpopulation fractions emerge from the molecular-level kinetics of gene networks and the division rates of single cells. To address this question we developed and quantitatively characterized an inducible, bistable synthetic gene circuit controlling the expression of a bifunctional antibiotic resistance gene in Saccharomyces cerevisiae. Following fitness and fluorescence measurements in two distinct environments (inducer alone and antibiotic alone), we applied a computational approach to predict cell population fitness and subpopulation fractions in the combination of these environments based on stochastic cellular movement in gene expression space and fitness space. We found that knowing the fitness and nongenetic (cellular) memory associated with specific gene expression states were necessary for predicting the overall fitness of cell populations in combined environments. We validated these predictions experimentally and identified environmental conditions that defined a “sweet spot” of drug resistance. These findings may provide a roadmap for connecting the molecular-level kinetics of gene networks to cell population fitness in well-defined environments, and may have important implications for phenotypic variability of drug resistance in natural settings

Proyecto, investigación e innovación en urbanismo, arquitectura y diseño industrial

Actas de congresoLas VII Jornadas de Investigación “Encuentro y Reflexión” y I Jornadas de Investigación de becarios y doctorandos. Proyecto, investigación e innovación en Urbanismo, Arquitectura y Diseño Industrial se centraron en cuatro ejes: el proyecto; la dimensión tecnológica y la gestión; la dimensión social y cultural y la enseñanza en Arquitectura, Urbanismo y Diseño Industrial, sustentados en las líneas prioritarias de investigación definidas epistemológicamente en el Consejo Asesor de Ciencia y Tecnología de esta Universidad Nacional de Córdoba. Con el objetivo de afianzar continuidad, formación y transferencia de métodos, metodología y recursos se incorporó becarios y doctorandos de los Institutos de investigación. La Comisión Honoraria la integraron las tres Secretarias de Investigación de la Facultad, arquitectas Marta Polo, quien fundó y María del Carmen Franchello y Nora Gutiérrez Crespo quienes continuaron la tradición de la buena práctica del debate en la cotidianeidad de la propia Facultad. Los textos que conforman las VII Jornadas son los avances y resultados de las investigaciones realizadas en el bienio 2016-2018.Fil: Novello, María Alejandra. Universidad Nacional de Córdoba. Facultad de Arquitectura, Urbanismo y Diseño; ArgentinaFil: Repiso, Luciana. Universidad Nacional de Córdoba. Facultad de Arquitectura, Urbanismo y Diseño; ArgentinaFil: Mir, Guillermo. Universidad Nacional de Córdoba. Facultad de Arquitectura, Urbanismo y Diseño; ArgentinaFil: Brizuela, Natalia. Universidad Nacional de Córdoba. Facultad de Arquitectura, Urbanismo y Diseño; ArgentinaFil: Herrera, Fernanda. Universidad Nacional de Córdoba. Facultad de Arquitectura, Urbanismo y Diseño; ArgentinaFil: Períes, Lucas. Universidad Nacional de Córdoba. Facultad de Arquitectura, Urbanismo y Diseño; ArgentinaFil: Romo, Claudia. Universidad Nacional de Córdoba. Facultad de Arquitectura, Urbanismo y Diseño; ArgentinaFil: Gordillo, Natalia. Universidad Nacional de Córdoba. Facultad de Arquitectura, Urbanismo y Diseño; ArgentinaFil: Andrade, Elena Beatriz. Universidad Nacional de Córdoba. Facultad de Arquitectura, Urbanismo y Diseño; Argentin

Parts & Pools: a framework for modular design of synthetic gene circuits

Published in 2008, Parts & Pools represents one of the □first attempts to conceptualizethe modular design of bacterial synthetic gene circuits with Standard Biological Parts (DNAsegments) and Pools of molecules referred to as common signal carriers (e.g. RNA polymerasesand ribosomes). The original framework for modeling bacterial components and designingprokaryotic circuits evolved over the last years and brought, fi□rst, to the development of analgorithm for the automatic design of Boolean gene circuits. This is a remarkable achievementsince gene digital circuits have a broad range of applications that goes from biosensors forhealth and environment care to computational devices. More recently, Parts & Pools wasenabled to give a proper formal description of eukaryotic biological circuit components. Thiswas possible by employing a rule-based modeling approach, a technique that permits a faithfulcalculation of all the species and reactions involved in complex systems such as eukaryoticcells and compartments. In this way, Parts & Pools is currently suitable for the visual andmodular design of synthetic gene circuits in yeast and mammalian cells too

Aptamers, Riboswitches, and Ribozymes in S. cerevisiae Synthetic Biology

Among noncoding RNA sequences, riboswitches and ribozymes have attracted the attention of the synthetic biology community as circuit components for translation regulation. When fused to aptamer sequences, ribozymes and riboswitches are enabled to interact with chemicals. Therefore, protein synthesis can be controlled at the mRNA level without the need for transcription factors. Potentially, the use of chemical-responsive ribozymes/riboswitches would drastically simplify the design of genetic circuits. In this review, we describe synthetic RNA structures that have been used so far in the yeast Saccharomyces cerevisiae. We present their interaction mode with different chemicals (e.g., theophylline and antibiotics) or proteins (such as the RNase III) and their recent employment into clustered regularly interspaced short palindromic repeats–CRISPR-associated protein 9 (CRISPR-Cas) systems. Particular attention is paid, throughout the whole paper, to their usage and performance into synthetic gene circuits

Novel S. cerevisiae Hybrid Synthetic Promoters Based on Foreign Core Promoter Sequences

Promoters are fundamental components of synthetic gene circuits. They are DNA segments where transcription initiation takes place. New constitutive and regulated promoters are constantly engineered in order to meet the requirements for protein and RNA expression into different genetic networks. In this work, we constructed and optimized new synthetic constitutive promoters for the yeast Saccharomyces cerevisiae. We started from foreign (e.g., viral) core promoters as templates. They are, usually, unfunctional in yeast but can be activated by extending them with a short sequence, from the CYC1 promoter, containing various transcription start sites (TSSs). Transcription was modulated by mutating the TATA box composition and varying its distance from the TSS. We found that gene expression is maximized when the TATA box has the form TATAAAA or TATATAA and lies between 30 and 70 nucleotides upstream of the TSS. Core promoters were turned into stronger promoters via the addition of a short UAS. In particular, the 40 nt bipartite UAS from the GPD promoter can enhance protein synthesis considerably when placed 150 nt upstream of the TATA box. Overall, we extended the pool of S. cerevisiae promoters with 59 new samples, the strongest overcoming the native TEF2 promoter