Microsoft Research, Trento, IT

Dynamic spatial games to understand cooperation in tumor formation

Authors: Matteo Cavaliere, Tarcisio Fedrizzi, Ferenc Jordán, Sean Sedwards & Attila Csikász-Nagy

Abstract: We propose a generative model, named "dynamic spatial game" (DSG) as an extension of "spatial game" proposed by Nowak and May [1]. DSG combines graph transformations and game theory to describe the role of cell-to-cell interactions during tissue formation and cancer development. The nodes of the graph represent cells and spatial interactions in the tissue are represented by the edges. Each cell acts as a player of a "game" where it interacts with its neighbors by sharing growth factors, apoptotic or anti-apoptotic signals etc., which determine the fitness of the cell. Depending on the gained fitness the cell divides, rests in G0 or dies. In the next step the graph is updated dynamically by adding or removing nodes, simulating a 2D tissue [2]. We test the role of cooperation in tissue formation and tumor development by simulating the dynamic spatial games of normal, mutated and multi-mutated (tumor) cells, where partially transformed mutated cells cooperate by sharing resources [3]. We investigate how the mutation rate and cooperation strength influences the timing of cancer development and discuss possible further extensions of the model to understand how cell-to-cell interactions influence cancer development.

[1] M. Nowak, R.M. May, (1992) Evolutionary games and spatial chaos, Nature, 359, 826 - 829.

[2] S. Bar-Duvdevani, L. Segel, (1994) On topological simulations in developmental biology, J Theor Biol, 166, 33-50.

[3] R. Axelrod, D.E. Axelrod, K.J. Pienta, (2006) Evolution of cooperation among tumor cells, PNAS, 103, 13474-9.

Computational Biology Group, University of Amsterdam, NL

Simple mechanics for biological phenomena

In this presentation we will talk about two very different applications of a similar model based on elementary mechanics.

The first application is a model of filamentous gliding bacteria which are sensitive to light fields and are capable of placing themselves quite precisely within the environment based on the light conditions. By simply projecting a light field on a culture of these microorganisms within a Petri dish, the population redistributes itself to reflect the projection, effectively imprinting whatever is projected onto the dish. Using a simple physical model for the filaments and equipping them with a realistic movement strategy, we reproduce the biological phenomenon.

The second application is the early development of the sea anemone Nematostella vectensis, which has been gaining momentum as a model organism in Evo-Devo. We use the same paradigm to create a model for the cells (blastomeres), which compose the hollow, multicell embryo (the blastula). These cells perform a process, called gastrulation, which essentially transforms the embryo from a monolayer epithelium into a bilayer and which is the first major event in development following fertilization. We enumerate the processes involved in this phenomenon and, using the computational model, assess the role of each towards the final result.