Papers by Maximino Aldana
In Gram negative bacteria, the multiple antibiotic resistance or mar operon, is known to control ... more In Gram negative bacteria, the multiple antibiotic resistance or mar operon, is known to control the expression of multi-drug efflux genes that protect bacteria from a wide range of drugs. Since different drugs induce this response, identifying the parameters that govern the dynamics of its induction is crucial to better characterize the process of tolerance and resistance. Most experiments have assumed that the properties of the mar transcriptional network can be inferred from population measurements. However, measurements from an asynchronous population of cells can mask underlying phenotypic variations of single cells. We monitored the activity of the mar promoter in single Escherichia coli cells in linear micro-colonies and established that the response to a steady level of inducer was heterogeneous within individual colonies. Specifically, sub-lineages defined by contiguous daughter-cells exhibited similar promoter activity, whereas activity was greatly variable between differe...
Frontiers in Physiology, 2021
ABSTRACTOver the last decades, analyses of the connectivity of large biological and artificial ne... more ABSTRACTOver the last decades, analyses of the connectivity of large biological and artificial networks have identified a common scale-free topology, where few of the network elements, called hubs, control many other network elements. In monitoring the dynamics of networks’ hubs, recent experiments have revealed that they can show behaviors oscillating between ‘on’ and ‘off’ states of activation. Prompted by these observations, we ask whether the existence of oscillatory hubs states could contribute to the emergence of specific network dynamical behaviors. Here, we use Boolean threshold networks with scale-free architecture as representative models to demonstrate how periodic activation of the network hub can provide a network-level advantage in learning specific new dynamical behaviors. First, we find that hub oscillations with distinct periods can induce robust and distinct attractors whose lengths depend upon the hub oscillation period. Second, we determine that a given network c...
Many complex diseases are expressed with high incidence only in certain populations. Genealogy st... more Many complex diseases are expressed with high incidence only in certain populations. Genealogy studies determine that these diseases are inherited with a high probability. However, genetic studies have been unable to identify the genomic signatures responsible for such heritability, as identifying the genetic variants that make a population prone to a given disease is not enough to explain its high occurrence within the population. This gap is known as the missing heritability problem. We know that the microbiota plays a very important role in determining many important phenotypic characteristics of its host, in particular, the complex diseases for which the missing heritability occurs. Therefore, when computing the heritability of a phenotype it is important to consider not only the genetic variation in the host but also in its microbiota. Here we test this hypothesis by studying an evolutionary model based on gene regulatory networks. Our results show that the holobiont (the host ...
INTER DISCIPLINA, 2020
Una propiedad importante de muchos sistemas complejos es la presencia de leyes de escalamiento, l... more Una propiedad importante de muchos sistemas complejos es la presencia de leyes de escalamiento, las cuales se caracterizan por el hecho de que las variables que describen el comportamiento del sistema se relacionan a través de leyes de potencias. Las leyes de escalamiento generalmente tienen dos implicaciones importantes: (i) la auto–similitud del sistema en un gran rango de escalas (cada parte del sistema se parece al sistema completo), y, (ii) los “eventos raros” (es decir, eventos poco probables) no son tan raros y ocurren mucho más frecuentemente de lo que se esperaría. En este trabajo discutimos la criticalidad dinámica como uno de los principales mecanismos que generan leyes de escalamiento en sistemas complejos, enfocándonos principalmente en modelos de formación de opiniones y en redes neuronales. Veremos que dos sistemas aparentemente muy distintos (redes de votantes y redes neuronales) pueden describirse prácticamente con las mismas herramientas conceptuales y metodológica...
Self-assembly is a spontaneous process through which macroscopic structures are formed from basic... more Self-assembly is a spontaneous process through which macroscopic structures are formed from basic microscopic constituents (e.g. molecules or colloids). By contrast, the formation of large biological molecules inside the cell (such as proteins or nucleic acids) is a process more akin to self-organization than to self-assembly, as it requires a constant supply of external energy. Recent studies have tried to merge self-assembly with self-organization by analyzing the assembly of self-propelled (or active) colloid-like particles whose motion is driven by a permanent source of energy. Here we present evidence that points to the fact that self-propulsion considerably enhances the assembly of polymers: self-propelled molecules are found to assemble into polymer-like structures, the average length of which increases towards a maximum as the self-propulsion force increases. Beyond this maximum, the average polymer length decreases due to the competition between bonding energy and disruptiv...
Frontiers in Physiology, 2018
Archives of medical research, Jan 20, 2018
The importance of microorganisms in human biology is undeniable. The amount of research that supp... more The importance of microorganisms in human biology is undeniable. The amount of research that supports that microbes have a fundamental role in animal and plant physiology is substantial and increasing every year. Even though we are only beginning to comprehend the broadness and complexity of microbial communities, evolutionary theories need to be recast in the light of such discoveries to fully understand and incorporate the role of microbes in our evolution. Fundamental evolutionary concepts such as diversity, heredity, selection, speciation, etc., which constitute the modern synthesis, are now being challenged, or at least expanded, by the emerging notion of the holobiont, which defines the genetic and metabolic networks of the host and its microbes as a single evolutionary unit. Several concepts originally developed to study ecosystems, can be used to understand the physiology and evolution of such complex systems that constitute "individuals." In this review, we discus...
Frontiers in Genetics, 2017
Wiley interdisciplinary reviews. Systems biology and medicine, 2016
Despite all the major breakthroughs in antibiotic development and treatment procedures, there is ... more Despite all the major breakthroughs in antibiotic development and treatment procedures, there is still no long-term solution to the bacterial antibiotic resistance problem. Among all the known types of resistance, adaptive resistance (AdR) is particularly inconvenient. This phenotype is known to emerge as a consequence of concentration gradients, as well as contact with subinhibitory concentrations of antibiotics, both known to occur in human patients and livestock. Moreover, AdR has been repeatedly correlated with the appearance of multidrug resistance, although the biological processes behind its emergence and evolution are not well understood. Epigenetic inheritance, population structure and heterogeneity, high mutation rates, gene amplification, efflux pumps, and biofilm formation have all been reported as possible explanations for its development. Nonetheless, these concepts taken independently have not been sufficient to prevent AdR's fast emergence or to predict its low s...
BMC Systems Biology, 2015
Background: The cAMP-dependent protein kinase regulatory network (PKA-RN) regulates metabolism, m... more Background: The cAMP-dependent protein kinase regulatory network (PKA-RN) regulates metabolism, memory, learning, development, and response to stress. Previous models of this network considered the catalytic subunits (CS) as a single entity, overlooking their functional individualities. Furthermore, PKA-RN dynamics are often measured through cAMP levels in nutrient-depleted cells shortly after being fed with glucose, dismissing downstream physiological processes. Results: Here we show that temperature stress, along with deletion of PKA-RN genes, significantly affected HSE-dependent gene expression and the dynamics of the PKA-RN in cells growing in exponential phase. Our genetic analysis revealed complex regulatory interactions between the CS that influenced the inhibition of Hsf1/Skn7 transcription factors. Accordingly, we found new roles in growth control and stress response for Hsf1/Skn7 when PKA activity was low (cdc25Δ cells). Experimental results were used to propose an interaction scheme for the PKA-RN and to build an extension of a classic synchronous discrete modeling framework. Our computational model reproduced the experimental data and predicted complex interactions between the CS and the existence of a repressor of Hsf1/Skn7 that is activated by the CS. Additional genetic analysis identified Ssa1 and Ssa2 chaperones as such repressors. Further modeling of the new data foresaw a third repressor of Hsf1/Skn7, active only in theabsence of Tpk2. By averaging the network state over all its attractors, a good quantitative agreement between computational and experimental results was obtained, as the averages reflected more accurately the population measurements. Conclusions: The assumption of PKA being one molecular entity has hindered the study of a wide range of behaviors. Additionally, the dynamics of HSE-dependent gene expression cannot be simulated accurately by considering the activity of single PKA-RN components (i.e., cAMP, individual CS, Bcy1, etc.). We show that the differential roles of the CS are essential to understand the dynamics of the PKA-RN and its targets. Our systems level approach, which combined experimental results with theoretical modeling, unveils the relevance of the interaction scheme for the CS and offers quantitative predictions for several scenarios (WT vs. mutants in PKA-RN genes and growth at optimal temperature vs. heat shock).
International Journal of Modern Physics B, 2009
In this work, we consider the phase transition from ordered to disordered states that occur in th... more In this work, we consider the phase transition from ordered to disordered states that occur in the Vicsek model of self-propelled particles. This model was proposed to describe the emergence of collective order in swarming systems. When noise is added to the motion of the particles, the onset of collective order occurs through a dynamical phase transition. Based on their numerical results, Vicsek and his colleagues originally concluded that this phase transition was of second order (continuous). However, recent numerical evidence seems to indicate that the phase transition might be of first order (discontinuous), thus challenging Vicsek's original results. In this work, we review the evidence supporting both aspects of this debate. We also show new numerical results indicating that the apparent discontinuity of the phase transition may in fact be a numerical artifact produced by the artificial periodicity of the boundary conditions.
Intelligent Systems Reference Library, 2011
Boolean threshold networks have recently been proposed as useful tools to model the dynamics of g... more Boolean threshold networks have recently been proposed as useful tools to model the dynamics of genetic regulatory networks, and have been successfully applied to describe the cell cycles of S. cerevisiae and S. pombe. Threshold networks assume that gene regulation processes are additive. This, however, contrasts with the mechanism proposed by S. Kauffman in which each of the logic functions must be carefully constructed to accurately take into account the combinatorial nature of gene regulation. While Kauffman Boolean networks have been extensively studied and proved to have the necessary properties required for modeling the fundamental characteristics of genetic regulatory networks, not much is known about the essential properties of threshold networks. Here we study the dynamical properties of these networks with different connectivities, activator-repressor proportions, activator-repressor strengths and different thresholds. Special attention is paid to the way in which the threshold value affects the dynamical regime in which the network operates and the structure of the attractor landscape. We find that only for a very restricted set of parameters, these networks show dynamical properties consistent with what is observed in biological systems. The virtues of these properties and the possible problems related with the restrictions are discussed and related to earlier work that uses these kind of models.
Lecture Notes in Physics
We address the question of the origin of three element coding units in the genetic code from the ... more We address the question of the origin of three element coding units in the genetic code from the point of view of the dynamics of primitive molecular machines. We uncover statistical regularities of generic electromagnetic interaction potentials of polymers moving in quasi ...
Physica A: Statistical Mechanics and its Applications, 1998
We characterize the dynamics of primitive molecular synthesis machines operating in outer space o... more We characterize the dynamics of primitive molecular synthesis machines operating in outer space on quasi-one-dimensional channels where polymers interact with ÿxed particles. We show that a generic property of particle=polymer electrostatic interactions is an average three monomer spacing between consecutive interaction potential minima. We exhibit that this property translates into locomotion regularities with a slowing down every three monomers. We argue that this transport property may be at the origin of the three base codon composition of the genetic code. We relate these ÿndings to present day protein synthesis mechanisms.
Origins of Life and Evolution of the Biosphere, 1996
Two fundamenta l questions associated with the origin of the genetic code are: 1) why in the t ra... more Two fundamenta l questions associated with the origin of the genetic code are: 1) why in the t ransla t ion to proteins are there three bases per codon, (n--3)? and 2) why does the nucleic acid a lphabet consist of four symbols, the four nucleotide bases, ( m = 4 ) ? We argue tha t the n = 3 value was forced by t ranslocat ion processes which took place in the R N A world. We show tha t under very general conditions the primitive replicating mechanisms opera t ing on polymers produced a locomotion dominated by shifts of three monomers. An "oppor tunis t ic" use of the t ranslocat ion mechanism then forced amino acid couplings and peptide syhthesis to conserve the.n--3 transpor t ing system. Under this scenario m--4 followed from an optimization process. Our result relies on generic' stat'istical t rends and is based on dynamical considerations of molecular machines operat ing at the so called "Brownian" regime where fluctuations play a major role.
Proceedings of the National Academy of Sciences, 2005
Two important theoretical approaches have been developed to generically characterize the relation... more Two important theoretical approaches have been developed to generically characterize the relationship between the structure and function of large genetic networks: The continuous approach, based on reaction-kinetics differential equations, and the Boolean approach, based on difference equations and discrete logical rules. These two approaches do not always coincide in their predictions for the same system. Nonetheless, both of them predict that the highly nonlinear dynamics exhibited by genetic regulatory systems can be characterized into two broad regimes, to wit, an ordered regime where the system is robust against perturbations, and a chaotic regime where the system is extremely sensitive to perturbations. It has been a plausible and long-standing hypothesis that genomic regulatory networks of real cells operate in the ordered regime or at the border between order and chaos. This hypothesis is indirectly supported by the robustness and stability observed in the phenotypic traits ...
Physica D: Nonlinear Phenomena, 2003
The dynamics of Boolean networks with scale-free topology are studied. The existence of a phase t... more The dynamics of Boolean networks with scale-free topology are studied. The existence of a phase transition from ordered to chaotic dynamics, governed by the value of the scale-free exponent of the network, is shown analytically by analyzing the overlap between two distinct trajectories. The phase diagram shows that the phase transition occurs for values of the scale-free exponent in the open interval (2, 2.5). Since the Boolean networks under study are directed graphs, the scale-free topology of the input connections and that of the output connections are studied separately. Ultimately these two topologies are shown to be equivalent. A numerical study of the attractor structure of the configuration space reveals that this structure is similar in both networks with scale-free topologies and networks with homogeneous random topologies. However, an important result of this work is that the fine-tuning usually required to achieve stability in the dynamics of networks with homogeneous random topologies is no longer necessary when the network topology is scale-free. Finally, based on the results presented in this work, it is hypothesized that the scale-free topology favors the evolution and adaptation of network functioning from a biological perspective.
Journal of Theoretical Biology, 2003
We address the question, related with the origin of the genetic code, of why are there three base... more We address the question, related with the origin of the genetic code, of why are there three bases per codon in the translation to protein process. As a followup to our previous work, [1, 2, 3] we approach this problem by considering the translocation properties of primitive molecular machines, which capture basic features of ribosomal/messenger RNA interactions, while operating under prebiotic conditions. Our model consists of a short one-dimensional chain of charged particles(rRNA antecedent) interacting with a polymer (mRNA antecedent) via electrostatic forces. The chain is subject to external forcing that causes it to move along the polymer which is fixed in a quasi one dimensional geometry. Our numerical and analytic studies of statistical properties of random chain/polymer potentials suggest that, under very general conditions, a dynamics is attained in which the chain moves along the polymer in steps of three 1 monomers. By adjusting the model in order to consider present day genetic sequences, we show that the above property is enhanced for coding regions. Intergenic sequences display a behavior closer to the random situation. We argue that this dynamical property could be one of the underlying causes for the three base codon structure of the genetic code
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Papers by Maximino Aldana