Abstract below

Nadya Morozova

CNRS UMR9019, Villejuif

Cell behavior in development and cancer

During development of living organisms, its shape evolves together with the differentiation of its parts. The laws governing the behavior of individual cells remain unrevealed. Differential gene expression is necessary but not sufficient to explain the formation of a precise geometry of an organism and its parts in space and time.
We suggest a mathematical formalization of cells behavior based on new concepts, that of cell state, determined by its position and epigenetic information, and cell event, which is a change of a cell state, with rules to convert epigenetic information into instructive signals for cell events. We then derive a graph with vertices corresponding to cell states and edges corresponding to 5 types of cell events: division, growth, death, movement and differentiation; and using this graph we characterize the shape of an organism at a given moment. Our Morphogenesis software simulates an evolution of a 3D embryo starting from zygote (Fig.). This allows investigating the rules and parameters of cells behavior during pattern formation, and the intriguing compatibility between determinism and variability of morphogenetic pathways.
Another subproject is an algorithm which allows calculating a distance between two developmental graphs and thus clustering them into groups. Next, the analysis of correspondence between the obtained clusters can elucidate the interrelation between developmental trends and formation of particular morphological structures.
Cancer progression differs from normal development. However, there are some internal regularities in cancer cells behavior, related to the balance of different subpopulations in a total cancer population, and to the possible modes of cell division – symmetric or asymmetric. Mathematical modeling of cancer cells behavior can elucidate the main parameters of cancer growth, important for predicting treatment results. We created a mathematical model of cancer cells population behavior, which allows investigating different scenarios of stem and non-stem cells behavior under different conditions (perturbation of sub-population balance, irradiation), and applied it for the sets of clinical data.

Illustration of Morphogenesis Software Configuration Page