Biology subjects

Valleriani, A.

Publications and source records attributed to Valleriani, A..

6 recordsLinked to original sources

bioRxiv2026

Dynamic cancer dormancy and awakening emerge from tumor microenvironment feedback in a minimal theoretical model

Cancer cell dormancy is characterized by late relapse and therapy resistance, yet the mechanisms that awaken dormant cells remain poorly understood. The tumor microenvironment has emerged as a key driver of these state transitions. Here we present a theoretical framework based on evolutionary game theory in which interactions between cancer and host cells are coupled explicitly to a changing tumor microenvironment. Cancer cells produce a conditioning factor that is cleared by the microenvironment and tolerated only up to a threshold. Through this conditioning factor, the microenvironment feeds back on cancer-host interactions and reshapes their competitive balance. Unlike a model with fixed interactions, this feedback allows dormancy and awakening to emerge as dynamic outcomes of microenvironmental change. We show that this minimal coupling is sufficient to generate distinct long-term regimes. Across these regimes, feedback generates thresholds and history dependence, so that the same cancer population can follow different fates depending on whether the microenvironment is already primed. Our framework reduces these dynamics to experimentally and biologically interpretable parameters linked to conditioning factor production, clearance, tolerance, and microenvironment-dependent changes in cancer-host competition. More broadly, it provides a quantitative basis for testing how collective microenvironmental feedback shapes cancer dormancy and awakening, and for designing experiments to uncover the mechanisms that awaken dormant cancer cells.

systems biology↗

bioRxiv2026

Mineralization kinetics during embryonic avian bone growth: a three-dimensional multiscale and cryogenic imaging approach

Bone formation during embryonic development requires the rapid and sustained delivery of large amounts of calcium to mineralizing tissue. In avian embryos, this process coincides with a unique physiological transition in calcium supply, shifting from limited yolk reserves to massive mobilization from the eggshell. To address the question of how calcium transport responds to the increasing mineral demand during this transition, we combine micro computed tomography with three-dimensional cryogenic FIB-SEM imaging at different embryonic stages in the developing quail femur. Over this developmental period, bone mineralized volume increases rapidly through periosteal expansion. We observe that bone forming cells consistently contain numerous membrane-bound carriers loaded with mineral precursors throughout all growth stages. By integrating measurements across length scales, we calculate the intracellular velocities required to sustain the observed mineral deposition in the successive developmental stages. Surprisingly, these velocities remain within a similar range across development, despite the significant difference of bone formation rates, and are consistent with active transport by molecular motors. The increasing mineral demand corresponds to the expansion of mineralizing surfaces, which leads to an increasing number of cells, while the transport capacity of individual cells remains similar. Our work reveals a perfect tuning between the calcium transport capacity and bone growth, even in a situation where the skeletal growth is accelerating in the quail embryo. Significance statementDespite the importance of bone mineralization for the integrity of the skeleton, surprisingly little is known about how calcium is transported across the organic matrix to the mineralization sites during embryonal development. Using an avian model, where the main source of calcium shifts from a limited contribution from the yolk to the massive reservoir in the eggshell, we quantify bone mineral deposition using tissue level characterization together with three-dimensional cryogenic nanoscale imaging. We discover that intracellular vesicles containing mineral precursors are transported at similar speed, although the overall mineral deposition rate is increasing six-fold from embryonal day 10 to 14. This shows that the acceleration in mineralization activity is due to an increased number of bone cells rather than to a larger workload for individual cells. These findings demonstrate that rapid bone development is regulated to synchronize growth rates and mineral transport.

physiology↗

bioRxiv2023

Phase diagrams of bone remodeling using a 3D stochastic cellular automaton

We propose a 3D stochastic cellular automaton model, governed by evolutionary game theory, to simulate bone remodeling dynamics. The model includes four voxel states: Formation, Quiescence, Resorption, and Environment. We simulate the Resorption and Formation processes on separate time scales to explore the parameter space and derive a phase diagram that illustrates the sensitivity of these processes to parameter changes. Combining these results, we simulate a full bone remodeling cycle. Furthermore, we show the importance of modeling small neighborhoods for studying local bone microenvironment controls. This model can guide experimental design and, in combination with other models, it could assist to further explore external impacts on bone remodeling. Consequently, this model contributes to an improved understanding of complex dynamics in bone remodeling dynamics and exploring alterations due to disease or drug treatment. Author summaryFunctional well-balanced bone remodeling is crucial for a healthy skeleton. Understanding the various causes for the disruption of this complex process requires models that combine behavior on micro- and macro-level. We propose a 3D stochastic cellular automaton model, where each voxel can take one of four different states representing phases of bone remodeling: Formation, Quiescence, Resorption and Environment. With a qualitative analysis, we show how and when small changes in key interaction parameters can make the difference between healthy and pathological bone remodeling. We also highlight the importance of spatial modeling and the size of the neighborhood for investigating local mechanisms. Our proposed model opens the window to explore the complex interplay of factors essential for healthy bone remodeling and potential alterations due to disease or drug treatment. In the long term this could help with the development of new treatment options for bone diseases.

systems biology↗

bioRxiv2020

A workbench for the translational control of gene expression

Ribosome profiling (Ribo-seq profiling) is the most advanced tool to study the translational control of gene expression. Unfortunately, the resolution of this cutting edge technique is severely limited by a low signal to noise ratio. To tackle this issue, we introduce here a newly designed statistical method for the identification of reproducible Ribo-seq profiles. In the case of E. coli, the analysis of 2238 Ribo-seq profiles across 9 independent datasets revealed that only 11 profiles are significantly reproducible. A subsequent data quality check led us to identify one outgroup dataset. By ruling it out, the number of highly reproducible profiles could be raised to 49. Despite its surprisingly small size, this set represents a reliable workbench to both assess the quality of the data and study the factors that influence the translation process.

bioinformatics↗

bioRxiv2020

A high-affinity antibody against the CSP N-terminal domain lacks Plasmodium falciparum inhibitory activity

Malaria is a global health concern and research efforts are ongoing to develop a superior vaccine to RTS,S/AS01. To guide immunogen design, we seek a comprehensive understanding of the protective humoral response against Plasmodium falciparum circumsporozoite protein (PfCSP). In contrast to the well-studied responses to the repeat region and the C-terminus, the antibody response against the N-terminal domain of PfCSP (N-CSP) remains obscure. Here, we characterized the molecular recognition and functional efficacy of the N-CSP-specific monoclonal antibody 5D5. The crystal structure at 1.85 [A] resolution revealed that 5D5 binds an -helical epitope in N-CSP with high affinity through extensive shape and charge complementarity, and the unusual utilization of an N-linked glycan. Nevertheless, functional studies indicated low 5D5 binding to live Pf sporozoites, and lack of sporozoite inhibition in vitro and in mosquitoes. Overall, our data on low recognition and inhibition of sporozoites do not support the inclusion of the 5D5 epitope into the next generation of CSP-based vaccines. Summary StatementThe Plasmodium falciparum sporozoite surface protein, PfCSP, is an attractive vaccine target, but the antibody response against the CSP N-terminal domain has remained understudied. Here, to guide immunogen design, Thai et al. provide insights into the binding motif and functional efficacy of the N-terminal domain-specific monoclonal antibody, 5D5.

immunology↗

bioRxiv2017

Integrative meta-analysis reveals that most yeast proteins are very stable

Measurements for protein half-lives in yeast Saccharomyces cerevisiae reported large discrepancies, with median values between minutes to several hours. We present a unifying analysis that provides a consistent half-life estimate, based on our re-analysis of three published and one new dataset of cells grown under similar conditions. We found that degradation of many proteins can be approximated by exponential decay. Protein disappearance was primarily driven by dilution due to cell division, with cell doubling times ranging from [~]2 to 3.5 hours across the four experiments. After adjusting for doubling time, protein half-lives increased to median values between [~]7.5 to [~]40 hours. Half-lives correlated with cell doubling time even after adjustment, implying that slow growth also slows protein degradation. All estimates were validated by multiple means and were robust to different analysis methods. Overall, protein stability correlated with abundance and showed weak enrichment for degradation signals such as degrons and disordered regions. Long-lived proteins often functioned in oxidation-reduction and amino acid synthesis. Short-lived proteins often functioned in ribosome biogenesis. Despite some overall differences in behavior, all methods were able to resolve subtle difference in half-lives of ribosomal proteins, e.g. the short lifespan of RPL10. Finally, our results help the design of future experiments: time series measurements need to cover at least two to three cell doubling times for accurate estimates, exponential decay provides a reasonable proxy for protein stability, and it can be sufficiently estimated with four measurement points.

systems biology↗