publications | Pablo Catalán

2024

Full factorial construction of synthetic microbial communities

Juan Diaz-Colunga^*, Pablo Catalán^*, Magdalena San Roman^*, Andrea Arrabal^*, and Alvaro Sanchez

eLife, 2024

Abs DOI PDF

Constructing combinatorially complete species assemblages is often necessary to dissect the complexity of microbial interactions and to find optimal microbial consortia. At the moment, this is accomplished through either painstaking, labor intensive liquid handling procedures, or through the use of state-of-the-art microfluidic devices. Here we present a simple, rapid, low-cost, and highly accessible liquid handling methodology for assembling all possible combinations of a library of microbial strains, which can be implemented with basic laboratory equipment. To demonstrate the usefulness of this methodology, we construct a combinatorially complete set of consortia from a library of eight Pseudomonas aeruginosa strains, and empirically measure the community-function landscape of biomass productivity, identify the highest yield community, and dissect the interactions that lead to its optimal function. This easy to implement, inexpensive methodology will make the assembly of combinatorially complete microbial consortia easily accessible for all laboratories.
Mathematical models of the Arabidopsis circadian oscillator

Lucas Henao, Saúl Ares, and Pablo Catalán

Biophysica, 2024

Abs DOI PDF

We review the construction and evolution of mathematical models of the Arabidopsis circadian clock, structuring the discussion into two distinct historical phases of modeling strategies: extension and reduction. The extension phase explores the bottom-up assembly of regulatory networks, introducing as many components and interactions as possible to capture the oscillatory nature of the clock. The reduction phase deals with functional decomposition, distilling complex models to their essential dynamical repertoire. Current challenges in this field, including the integration of spatial considerations and environmental influences like light and temperature, are also discussed. The review emphasizes the ongoing need for models that balance molecular detail with practical simplicity.

2023

Discovery and molecular basis of chloride as an allosteric activator and catalytic inhibitor for Class-D β-lactamases

Qi Zhou^*, Pablo Catalán^*, Helen Bell^*, Patrick Baumann, Rhodri Evans, Jianhua Yang, Zhen Zhang, Davide Zappala, Ye Zhang, George Michael Blackburn, Yuan He, and Yi Jin

ACS Central Science, 2023

Abs DOI PDF Supp

Antibiotic-resistant Enterobacterales that produce oxacillinase (OXA)-48-like Class D β-lactamases are often linked to increased clinical mortality. Though the catalytic mechanism of OXA-48 is known, the molecular origin of its biphasic kinetics has been elusive. We here identify selective chloride binding rather than decarbamylation of the carbamylated lysine as the source of biphasic kinetics, utilizing isothermal titration calorimetry (ITC) to monitor the complete reaction course with the OXA-48 variant having a chemically stable N-acetyl lysine. Further structural investigation enables us to capture an unprecedented inactive acyl intermediate wedged in place by a halide ion paired with a conserved active site arginine. Supported by mutagenesis and mathematical simulation, we identify chloride as a “Janus effector” that operates by allosteric activation of the burst phase and by inhibition of the steady state in kinetic assays of β-lactams. We show that chloride-induced biphasic kinetics directly affects antibiotic efficacy and facilitates the differentiation of clinical isolates encoding Class D from Class A and B carbapenemases. As chloride is present in laboratory and clinical procedures, our discovery greatly expands the roles of chloride in modulating enzyme catalysis and highlights its potential impact on the pharmacokinetics and efficacy of antibiotics during in vivo treatment.
Entropic contribution to phenotype fitness

Pablo Catalán, Juan Antonio Garcı́a-Martı́n, Jacobo Aguirre, José A Cuesta, and Susanna Manrubia

Journal of Physics A: Mathematical and Theoretical, 2023

Abs DOI

All possible phenotypes are not equally accessible to evolving populations. In fact, only phenotypes of large size, i.e. those resulting from many different genotypes, are found in populations of sequences, presumably because they are easier to discover and maintain. Genotypes that map to these phenotypes usually form mostly connected genotype networks that percolate the space of sequences, thus guaranteeing access to a large set of alternative phenotypes. Within a given environment, where specific phenotypic traits become relevant for adaptation, the replicative ability of a phenotype and its overall fitness (in competition experiments with alternative phenotypes) can be estimated. Two primary questions arise: how do phenotype size, reproductive capability and topology of the genotype network affect the fitness of a phenotype? And, assuming that evolution is only able to access large phenotypes, what is the range of unattainable fitness values? In order to address these questions, we quantify the adaptive advantage of phenotypes of varying size and spectral radius in a two-peak landscape. We derive analytical relationships between the three variables (size, topology, and replicative ability) which are then tested through analysis of genotype-phenotype maps and simulations of population dynamics on such maps. Finally, we analytically show that the fraction of attainable phenotypes decreases with the length of the genotype, though its absolute number increases. The fact that most phenotypes are not visible to evolution very likely forbids the attainment of the highest peak in the landscape. Nevertheless, our results indicate that the relative fitness loss due to this limited accessibility is largely inconsequential for adaptation.

2022

COP1 dynamics integrate conflicting seasonal light and thermal cues in the control of Arabidopsis elongation

Cristina Nieto^*, Pablo Catalán^*, Luis Miguel Luengo, Martina Legris, Vadir López-Salmerón, Jean Michel Davière, Jorge J Casal, Saúl Ares, and Salomé Prat

Science Advances, 2022

Abs DOI

As the summer approaches, plants experience enhanced light inputs and warm temperatures, two environmental cues with an opposite morphogenic impact. Key components of this response are PHYTOCHROME B (phyB), EARLY FLOWERING 3 (ELF3), and CONSTITUTIVE PHOTOMORPHOGENIC 1 (COP1). Here, we used single and double mutant/overexpression lines to fit a mathematical model incorporating known interactions of these regulators. The fitted model recapitulates thermal growth of all lines used and correctly predicts thermal behavior of others not used in the fit. While thermal COP1 function is accepted to be independent of diurnal timing, our model shows that it acts at temperature signaling only during daytime. Defective response of cop1-4 mutants is epistatic to phyB-9 and elf3-8, indicating that COP1 activity is essential to transduce phyB and ELF3 thermosensory function. Our thermal model provides a unique toolbox to identify best allelic combinations enhancing climate change resilience of crops adapted to different latitudes.
Seeking patterns of antibiotic resistance in ATLAS, an open, raw MIC database with patient metadata

Pablo Catalán, Emily Wood, Jessica MA Blair, Ivana Gudelj, Jonathan R Iredell, and Robert E Beardmore

Nature Communications, 2022
The long and winding road to understanding organismal construction: Reply to comments on" From genotypes to organisms: State-of-the-art and perspectives of a cornerstone in evolutionary dynamics"

Susanna Manrubia, José A Cuesta, Jacobo Aguirre, Sebastian E Ahnert, Lee Altenberg, Alejandro V Cano, Pablo Catalán, Ramon Diaz-Uriarte, Santiago F Elena, Juan Antonio Garcı́a-Martı́n, Paulien Hogeweg, Bhavin S. Khatri, Joachim Krug, Ard A. Louis, Nora S. Martin, Joshua L. Payne, Matthew Tarnowski, and Marcel Weiß

Physics of Life Reviews, 2022

2021

From genotypes to organisms: State-of-the-art and perspectives of a cornerstone in evolutionary dynamics

Susanna Manrubia, José A Cuesta, Jacobo Aguirre, Sebastian E Ahnert, Lee Altenberg, Alejandro V Cano, Pablo Catalán, Ramon Diaz-Uriarte, Santiago F Elena, Juan Antonio Garcı́a-Martı́n, Paulien Hogeweg, Bhavin S. Khatri, Joachim Krug, Ard A. Louis, Nora S. Martin, Joshua L. Payne, Matthew Tarnowski, and Marcel Weiß

Physics of Life Reviews, 2021
The Antibiotic Dosage of Fastest Resistance Evolution: gene amplifications underpinning the inverted-U

Carlos Reding, Pablo Catalán, Gunther Jansen, Tobias Bergmiller, Emily Wood, Phillip Rosenstiel, Hinrich Schulenburg, Ivana Gudelj, and Robert Beardmore

Molecular Biology and Evolution, 2021

2020

Populations of genetic circuits are unable to find the fittest solution in a multilevel genotype–phenotype map

Pablo Catalán, Susanna Manrubia, and José A Cuesta

Journal of the Royal Society Interface, 2020

2019

Parsimonious scenario for the emergence of viroid-like replicons de novo

Pablo Catalán, Santiago F Elena, José A Cuesta, and Susanna Manrubia

Viruses, 2019

2018

Statistical theory of phenotype abundance distributions: a test through exact enumeration of genotype spaces

Juan Antonio Garcıa-Martın, Pablo Catalán, Susanna Manrubia, and José A Cuesta

Europhysics Letters, 2018
On the networked architecture of genotype spaces and its critical effects on molecular evolution

Jacobo Aguirre, Pablo Catalán, José A Cuesta, and Susanna Manrubia

Open biology, 2018
Adding levels of complexity enhances robustness and evolvability in a multilevel genotype–phenotype map

Pablo Catalán, Andreas Wagner, Susanna Manrubia, and José A Cuesta

Journal of The Royal Society Interface, 2018

2017

Adaptive multiscapes: an up-to-date metaphor to visualize molecular adaptation

Pablo Catalán, Clemente F Arias, Jose A Cuesta, and Susanna Manrubia

Biology direct, 2017
Estimating wind dispersal potential in Ailanthus altissima: The need to consider the three-dimensional structure of samaras

Greg Planchuelo, Pablo Catalán, Juan Antonio Delgado, and Antonio Murciano

Plant Biosystems-An International Journal Dealing with all Aspects of Plant Biology, 2017

2016

Sink strength manipulation in branches of a Mediterranean woody plant suggests sink-driven allocation of biomass in fruits but not of nutrients in seeds

Pablo Catalán, Juan A Delgado, Marı́a D Jiménez, and Luis Balaguer

Acta physiologiae plantarum, 2016
Gone with the wind and the stream: Dispersal in the invasive species Ailanthus altissima

Greg Planchuelo, Pablo Catalán, and Juan Antonio Delgado

Acta oecologica, 2016

2015

Mutation-selection equilibrium in finite populations playing a Hawk–Dove game

Pablo Catalán, Jesús M Seoane, and Miguel AF Sanjuán

Communications in Nonlinear Science and Numerical Simulation, 2015

2014

toyLIFE: a computational framework to study the multi-level organisation of the genotype-phenotype map

Clemente F Arias, Pablo Catalán, Susanna Manrubia, and José A Cuesta

Scientific reports, 2014

2013

Comparing the allelopathic potential of exotic and native plant species on understory plants: are exotic plants better armed?

Pablo Catalán, Beatriz R Vázquez-de-Aldana, Paloma Heras, Alberto Fernández-Seral, and M Esther Pérez-Corona

2013