Biology subjects

San Roman, M.

Publications and source records attributed to San Roman, M..

7 recordsLinked to original sources

bioRxiv2026

Statistical learning of bacterial growth in combinatorially constructed environments

Optimizing growth conditions and culture media is a major goal in microbiology. A challenge is that nutrients can have complex, non-additive effects on growth. The fact that resources interact with one another has long been known in ecology, but systematic maps of resource interactions at all orders have been lacking and it is not known whether interactions are primarily low order or fundamentally complex. To tackle this problem, we have followed a full factorial design approach and measured the growth of seven different bacterial species in all possible combinations of 8 carbon sources under carbon-limiting conditions. Our approach allows us to directly estimate interactions at all orders. Even though all C-sources stimulate growth on their own as well as in combination with other nutrients, most of them can also have negative effects on growth when they are added to at least some nutrient mixtures. We show that the switch from positive to negative fitness effects is governed by global epistasis among resources. An analysis of variance shows that additive effects and pairwise interactions explain most of the variation in fitness, allowing us to train simple regression models that accurately predict bacterial growth in novel environments. The generality of these findings across seven different bacterial strains belonging to two different families indicates that interactions between carbon sources under carbon-limiting conditions may be generally learnable from a relatively sparse set of constructed environments, enabling the rational optimization of growth conditions.

microbiology↗

bioRxiv2026

Coupled nucleoplasmic flows and envelope expansion govern the mechanical resistance of the nucleus

In recent year, it became clear that the cell nucleus can undergo large deformations, during immune cell migration and tumor growth. These deformations generate signals that allow cells to sense their environment and adapt to it. How cells cope with and respond to large deformations thus strongly depends on the nuclear mechanics, but our understanding of the physical properties of the nucleus remains incomplete. In particular, it is not clear how the nuclear volume responds to deformation. Here we combine controlled confinement assays, high-resolution imaging and atomic force microscopy with theoretical modelling to propose a physical model of the cell nucleus that accounts for its surface and bulk properties and addresses both steady-state and transient regimes. Our results establish the nucleus as a poroelastic body in which mechanics are dominated by the envelope and dynamics by the chromatin, and suggest that regulating water permeability may be as important as softening the envelope for cells migrating rapidly through dense tissues.

biophysics↗

bioRxiv2025

misosoup: A metabolic modeling tool for identifying minimal microbial communities reveals pervasive cross-feeding-driven niche expansion

Microbial survival and function often depend on metabolic interactions within communities. Therefore, a central question in disentangling microbial organization is determining which minimal groups of species are able to thrive in a given medium - referred to as "minimal communities". Answering this question is essential for understanding microbial distribution, enhancing laboratory cultivation, and designing synthetic communities (SynComs). Here, we introduce misosoup, a Python package for identifying minimal communities (MInimal Supplying community Search). Through genome-scale constraint-based metabolic modeling, misosoup enables the systematic identification of communities that support microbial growth in environments where individual species fail to survive alone. We validate misosoup against experimentally verified minimal communities, demonstrating its ability to predict known cooperative interactions, cocultures, and consortia with biotechnological potential. We further illustrate the use of misosoup to investigate broad microbial ecology questions by applying it to a set of 60 marine microbes, finding pervasive cross-feeding-driven niche expansion, and showing how the detailed outputs provided by misosoup facilitate research on hot topics such as the identification of functional groups. In summary, misosoup provides a powerful tool for microbial ecology and community design, with potential applications in both research and biotechnological innovation. ImportanceMicrobes often rely on each other to survive, especially in environments where they cant live alone. Understanding which small groups of microbes can thrive together--called minimal communities--is key to improving lab research, designing synthetic ecosystems, and exploring how microbes spread in nature. To support this, we developed misosoup, a Python tool that identifies these communities using advanced metabolic modeling. misosoup helps scientists discover how microbes cooperate by sharing nutrients, a process known as metabolic cross-feeding. When tested on sets of species from different origins, the tool showed that species could thrive in more environments when part of a group. This highlights the importance of teamwork in microbial life. misosoup not only predicts these interactions but also provides detailed insights that can guide ecological studies and biotechnological innovation. By revealing how microbes support each other, misosoup contributes to a deeper understanding of lifes interconnectedness and offers tools for solving real-world challenges.

bioinformatics↗

bioRxiv2024

The Arp2/3 complex maintains genome integrity and survival of epidermal Langerhans cells

Myeloid cells use intracellular actin networks for key cellular processes, including cell migration and chemotaxis, phagocytosis or macropinocytosis, as well as immune synapse formation. However, whether actin networks play any role in the development and/or survival of myeloid cells in tissues remains open. Here, we found that the Arp2/3 complex, which is responsible for the nucleation of branched actin networks, is needed for in vivo maintenance of epidermal Langerhans cells (LCs) throughout life. Mice harboring a genetic deletion of the Arpc4 subunit of the complex in myeloid cells form LC networks at birth, but these cells decline in numbers following a process reminiscent of premature cellular aging. By combining in vivo analyses of LCs with in vitro experiments on bone-marrow-derived dendritic cells, we found that Arpc4-deficient cells manage to progress through the cell cycle but accumulate DNA damage associated with aberrant nuclear shapes, lamina reduction and events of nuclear envelope rupture. These results provide the first evidence for a physiological role of Arp2/3 in maintenance of genome integrity and survival of immune cells in tissues.

cell biology↗

bioRxiv2024

Ecological dynamics explain modular denitrification in the ocean

Microorganisms in marine oxygen minimum zones (OMZs) drive globally impactful biogeochemical processes. One such process is the multi-step denitrification, the dominant pathway for bioavailable nitrogen (N) loss and nitrous oxide (N2O) production. Denitrification-derived N loss is typically measured and modeled as a single step, but observations reveal that most denitrifiers in OMZs contain only subsets ("modules") of the complete pathway. Here, we identify the ecological mechanisms sustaining diverse denitrifiers, explain the observed prevalence of certain modules, and examine the implications for N loss. We describe microbial functional types carrying out diverse denitrification modules by their underlying redox chemistry, constraining their traits with thermodynamics and pathway length penalties, in an idealized OMZ ecosystem model. Biomass yields of single-step modules increase along the denitrification pathway when growth is limited by organic matter (OM), explaining the viability of populations respiring nitrite and N2O in a nitrate-filled ocean. Results predict denitrifier community succession along environmental gradients: shorter versus longer modules are favored when OM versus N limits growth, respectively, suggesting a niche for the NO3-{longrightarrow}NO2- module in free-living communities and for the complete pathway in organic particles, consistent with observations. The model captures and mechanistically explains the observed dominance and higher oxygen tolerance of the NO3-{longrightarrow}NO2- module. Results also capture observations that nitrate is the dominant source of N2O. These results advance the mechanistic understanding of the relationship between microbial ecology and N loss, which is essential for accurately predicting the oceans future.

ecology↗

bioRxiv2024

Full factorial construction of synthetic microbial communities

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.

ecology↗

bioRxiv2018

Actomyosin-driven force patterning controls endocytosis at the immune synapse

An important channel of cell-to-cell communication is direct contact. The immune synapse is a paradigmatic example of such type of interaction: it forms upon engagement of antigen receptors in lymphocytes by antigen-presenting cells and allows the local exchange of molecules [1]. Although [2], how forces organize and mechanics has been shown to play an important role in this process impact on synapse function is unknown. We found that mechanical forces are spatio-temporally patterned at the immune synapse: global contractile forces are observed at the synapse periphery and local point-like forces are detected at its centre. The global contractile forces result from a pulsatile centripetal actomyosin flow that leads to formation of F-actin protrusions from which the central point like forces emerge. Noticeably, these force-producing actin protrusions constitute the main site of antigen extraction and endocytosis. Accordingly, deletion of the myosin IIA gene leads to impaired B cell responses. The interplay between global and local forces governed by the actomyosin cytoskeleton therefore controls the endocytic function of the immune synapse and might constitute a more general mechanism in the physical regulation of cell-cell interactions.

cell biology↗