Walter de Back

Morpheus: Multi-scale modeling of cellular systems

Developmental biology seeks to understand how a single fertilized egg develops into an organism. Modern high through-put and image analysis techniques provide unprecedented detailed data. However, such analysis must be complemented with mathematical and computational modeling to yield new insight.

We have developed Morpheus: a modeling and simulation environment for multi-scale studies of developmental systems. The simulation platform allows users to model intracellular dynamics using differential equation), model cellular shape and motility using a cellular Potts model, and model diffusive signaling using reaction-diffusion systems. The various levels can be easily coupled using a flexible symbolic description language.

Morpheus is being used in a wide range of studies in development, morphogenesis, and organogenesis.

Collaborators: Jörn Starruß, Andreas Deutsch

Virtual liver

The liver is a multifunctional organ participating in a wide number of essential physiological processes, and exhibits a remarkable ability of regeneration. The liver consists of a large number of liver lobules, whose spatial structure serves to allows blood to contact hepatocytes, the cell type that makes up 80% of the organ.

We participate in a BMBF-funded Systems Biology network that aims to construct a integrated whole-organ computational model of the liver. In our project, we focus on the hepatic-sinusoidal unit as the minimal functional unit in liver organization.

Using experimental data from in vitro co-cultures of hepatocytes and sinusoidal cells, we aim to understand the (re)establishment of functional organization of the basic liver unit in a computational cell-based model.

Collaborators: Virtual Liver network

Pancreas organogenesis

Predicting cell fate decisions of pancreatic cells is crucial to develop new replacement or regenerative therapies to treat diabetes. Many transcription factors and signaling pathways involved in this decision have already been identified. However, it remains unclear how they interact at the system's level.

We are developing a multiscale model of pancreac organogenesis that integrates known mechanisms on gene regulation, intercellular signaling and morphogenesis into a dynamic integrative model.

Collaborators: Joseph Xu Zhou (Canada) and Lutz Brusch

Vasculogenesis

Vasculogenesis is the de novo formation of blood vessels from isolated endothelial cell precursors called angioblasts. During the early stages of embryogenesis, angioblasts aggregate into a network-like, proto-vascular system.

We develop a computational cell-based model to study the formation of such capillary networks (see figure). Angioblasts are modeled in a microenvironment of VEGF and fibronectin, which provides the signalling cues for the development of realistic vascular networks by way of haptotaxis.

We compare the spatio-temporal development of the in silico network to data from confocal microscopy of in vivo vasculogenesis in chick embryos.

Collaborators: Álvaro Köhn Luque (Madrid/Malaga), Miguel A. Herrero (Madrid) and José M. Pérez-Pomares (Malaga)

Through endocytosis, cells can internalize large molecules that otherwise cannot pass through the membrane (see figure). Mammalian cells have distinct types of internalized vesicles, endosomes, that take care of transport, sorting, and degrading cargo.

We study endocytic trafficking by focusing on the population of early (Rab5) endosomes. Extensive experimental data is available from live-cell imaging techniques. Using an agent-based model, we aim to identify the key biophysical mechanisms responsible for robust endosomal trafficking in healthy mammalian cells.

Collaborators: Martin Sander, Jonathan Dawson, Roberto Villasenor, Frank Jülicher, Marino Zerial

Prebiotic evolution

The study of the pre-biological chemical systems is an approach to understand the organizational principles of living systems in general. By theoretical analysis and simulation, we aim to sketch a potential scenario on the evolutionary path from mere chemistry towards a minimal form of life.

Our focus is on early RNA world scenarios, in which RNA acts as both genetic information and enzymatic catalyst. Specifically, we study the way in which specific catalytic RNA molecules emerge and self-structure into simple metabolic pathways. And, as such, construct an infrabiological system comprising primitive generic and metabolic subsystems, providing key prerequisites for early protocellular life.

Collaborators: Sergio Branciamore (Duarte, USA) and Eörs Szathmáry (Budapest)