Biology subjects

Botte, E.

Publications and source records attributed to Botte, E..

4 recordsLinked to original sources

bioRxiv2024

Evolvoid: A genetic algorithm for shaping optimal cellular constructs

We describe an in-silico pipeline, Evolvoid, based on Genetic Algorithms (GAs) for identifying the optimal morphologies of cell-laden constructs. Driven by an ad hoc selection rule (i.e., the so-called fitness function (FF)), Evolvoid iteratively identifies the characteristics (i.e., the genome) of the survival of the fittest individual of a given population throughout generations. The FF is based on universally observed biophysical laws, representing the optimal trade-off between i) high cell viability and robustness to changes in environmental oxygen and ii) a low surface energy. The Shannon entropy is used to evaluate genome complexity, with the most complex fittest individuals showing quantitative and qualitative biological resemblance to in vitro constructs. Evolvoid paves the way for the development of "lab on a laptop": high-fidelity and cost-effective digital twins of cellular constructs which could augment or even substitute costly in vitro models.

bioengineering↗

bioRxiv2023

Variability in single-cell oxygen consumption kinetics

We combined microfabricated devices with multiparameter identification algorithms to probe the variability in size-dependent oxygen consumption parameters of single human hepatic cells. We demonstrate that single cells exhibit an oxygen-dependent metabolic rate, typical of Michaelis-Menten kinetics, and that their maximal oxygen consumption is significantly lower than that of monolayers or 3D hepatic cell aggregates. Notably, we found that clusters of two or more cells competing for a limited oxygen supply reduced their maximal single-cell consumption rate, highlighting their ability to adapt to local resource availability and the presence of nearby cells. Next, we used our high-throughput approach to characterize the covariance of size and oxygen consumption within a cell population. The results show that cooperative behaviour emerges in cell clusters, and that single-cell size and metabolism can be described by a lognormal joint probability density. Our study thus serves as a foundation to connect the metabolic activity of single human hepatocytes to their tissue-or organ-level metabolism as well as describe its size-related variability through scaling laws.

bioengineering↗

bioRxiv2022

Stable population structure in Europe since the Iron Age, despite high mobility

Ancient DNA research in the past decade has revealed that European population structure changed dramatically in the prehistoric period (14,000-3,000 years before present, YBP), reflecting the widespread introduction of Neolithic farmer and Bronze Age Steppe ancestries. However, little is known about how population structure changed from the historical period onward (3,000 YBP - present). To address this, we collected whole genomes from 204 individuals from Europe and the Mediterranean, many of which are the first historical period genomes from their region (e.g. Armenia and France). We found that most regions show remarkable inter-individual heterogeneity. At least 7% of historical individuals carry ancestry uncommon in the region where they were sampled, some indicating cross-Mediterranean contacts. Despite this high level of mobility, overall population structure across western Eurasia is relatively stable through the historical period up to the present, mirroring geography. We show that, under standard population genetics models with local panmixia, the observed level of dispersal would lead to a collapse of population structure. Persistent population structure thus suggests a lower effective migration rate than indicated by the observed dispersal. We hypothesize that this phenomenon can be explained by extensive transient dispersal arising from drastically improved transportation networks and the Roman Empires mobilization of people for trade, labor, and military. This work highlights the utility of ancient DNA in elucidating finer scale human population dynamics in recent history.

genetics↗

bioRxiv2021

An integrated pipeline and multi-model graphical user interface for accurate nano-dosimetry

Accurate dosing of nanoparticles is crucial for risk assessment and for their safe use in medical and other applications. Although it is well-known that nanoparticles sediment, diffuse and aggregate as they move through a fluid, and that therefore the effective dose perceived by cells may not necessarily be that initially administered, dose quantification remains a challenge. This is because to date, methods for accurate dose estimation are difficult to implement, involving precise characterization of the nanomaterial and the exposure system as well as complex mathematical operations. Here we present a pipeline for accurate nano-dosimetry of engineered nanoparticles on cell monolayers, based on an easy-to-use graphical software - DosiGUI - which integrates two well-established particokinetic and particodynamic models. DosiGUI is an open source tool which was developed to facilitate nano-dosimetrics. The pipeline includes methods for determining the stickiness index which describes the affinity between nanoparticles and cells. Our results show that accurate estimations of the effective dose cannot prescind from rigorous characterization of the stickiness index, which depends on both nanoparticle characteristics and cell type.

pharmacology and toxicology↗