CDEV Subgroup Contributed Talks

Tim Liebisch

Goethe Universität Frankfurt

"Mathematical Modelling Identifies Core Principles of Epithelial Organoid Dynamics"

Epithelial organoids are three-dimensional cell culture systems mimicking aspects of organ development and disease. Pancreas organoids are found to be very heterogeneous in culture and exhibit diverse, dynamic behaviour. One example is frequent size oscillations, which are hypothesised to occur in response to an interplay of the elasticity and the production of an osmotic active substance by the cell monolayer, as increasing osmotic pressure can lead to rupture of the cellular contacts, allowing the pressure to relax.Mathematical modelling allowed us to extract core principles driving these size oscillations of the organoids. By deriving a scaling law from the organoid dynamics, we can identify a dependence of the observed size oscillations and the cell proliferation dynamics. Furthermore, size oscillations also depend on the surface-to-volume ratio, hence, on the organoid size. A biomechanical 3D agent-based model confirms these mathematical considerations.The implemented model allows investigation of the interplay of the elasticity of the cells and their production rate in more detail and further observed phenomena such as organoid rotation.

David M. Versluis

Leiden University, Leiden, the Netherlands

"How Oxygen and Lactose Metabolism Shape the Infant Gut Microbiota"

Nearly immediately after birth, a complex and dynamic ecosystem forms in the human infant gut. The characteristics of this system influence the infant's health in both the short and long term. 2'-FL, the most prevalent prebiotic in most human milk, varies greatly in presence and concentration between individuals. We use a multi-scale spatiotemporal model of the infant colon from birth to three weeks of age to reproduce the effects of variations in nutritional components on the composition and metabolic activity of the microbiota. Using flux balance analysis with molecular crowding on genome-scale metabolic models from the AGORA project, we calculate bacterial fluxes for different locations and time points at a high resolution. The resulting fluxes are integrated together into a model of the ecosystem that feeds back into the flux calculations. The model can give insight and produce predictions for bacterial and metabolic composition of the infant microbiota over time and under different conditions. Our aim is to reach a deeper understanding of the influence that nutrition can have on the development of the infant microbiota. This in turn is the first step towards a comprehensive understanding of the formation of a steady state adult microbial environment.

Renske Vroomans

University of Amsterdam, Origins Center

"Evolution of selfish multicellularity"

Recent studies have shown that many functions of multicellular organisms were already present in their unicellular ancestors. For instance, many gene families involved in animal development and cell adhesion can also be found in unicellular relatives. This indicates that the evolutionary transition to multicellularity predominantly required changes in regulation and coordination, more than gene content. We use an evolutionary cell-based model to show that the emergent collective behaviour of multicellular clusters can drive the evolution of adhesion. We then extend this model to investigate how regulation of cell behaviour evolves in concert with the evolution of multicellularity. Cells have an evolvable gene regulatory network that determines when they divide and migrate. We observe that evolution of adhesion changes cell competition dynamics: cells evolve adhesion to migrate collectively and to get closer to resources. Within such cohesive clusters, competition drives cells to divide first, and then migrate to resources. When cells cannot evolve adhesion, cells instead migrate to reach resources first and then divide, blocking their competitors. Thus, the model demonstrates how the transition to multicellularity may have driven a drastic switch in cell behaviour, leading to complex coordinated dynamics compared to the unicellular cousins, without changing the genetic toolkit.

John Fozard

John Innes Centre

"Diffusion-mediated coarsening can explain crossover pattening in meiosis"

Meiosis, the special cell divisions occurring prior to sexual reproduction, is a crucial process for most organisms.Early during meiosis, the chromosomes encoding the same genes group together to form linear structures.At a small number of points along these structures the DNA strands form crossovers, splicing together chromosomes and exchanging genetic information.These crossovers tend to be much more regularly spaced than would be expected by chance, and the mechanism controlling this is a long-standing open question.We have developed a model for crossover patterning, in which a protein diffuses along the one-dimensional structure, and is able to aggregate at a number of discrete foci.Competition between the foci for the protein leads to coarsening, selecting those foci that will become crossovers.This will allow us to explain many of the elements of crossover positioning in the model plant Arabidopsis thaliana, and we will show that it agrees well with our experimental observations.