Daniella Schittler

Research interests

Modeling and analysis of genetic switches in stem cell differentiation Differentiation of stem cells can be viewed as subsequent cell fate decisions, corresponding to increasing specialization. We develop generic models for these cell fate switches [Schittler et al., Chaos 2010] and use them to analyze the multistability and dynamical properties of such systems. For the selection of generic network structures, we can make use of a qualitative, yet ODE-based modeling framework. [ Schittler & Breindl et al., IFAC 2011] Furthermore, we develop analysis and construction methods to extend such generic models to more detailed, higher-dimensional gene regulatory network models. These can then be used, together with gene expression time series data, to estimate gene interaction parameters and predict the effect of differentiation stimuli on the cell fate. Taken together, this allows us to test hypotheses about gene regulation networks, to analyze or even predict the system behavior under given hypotheses, and eventually to deduce control strategies.
Models for proliferating cell populations and labeling experiments The study of cell proliferation is a very important field not only in stem cell research and immunology. Numerous models have been developed over the last decade that either focus on the numbers of divisions that cells undergo, or on the label intensity of commonly used fluorescent dyes (such as CFSE or BrdU). We have developed a new model that incorporates both - the division number as well as the label intensity - and thereby is especially suited to exploit data from proliferation assays [ Schittler & Hasenauer et al., WCSB 2011; Hasenauer, Schittler et al., Bull. Math. Biol. 2012]. Furthermore, we have extended our model class to account for crucial properties such as cell types with distinct proliferation properties [ Schittler et al., WCSB 2012], or label specificities such as heterogeneous BrdU uptake [in prep.].
Interdisciplinary collaborations for bone tissue engineering The research interests mentioned are particularly motivated by tissue engineering of bone transplants: In this project, mesenchymal stem cells are differentiated into bone cells (osteoblasts) which should finally build a complete human bone. The high number and complexity of intra- and intercellular processes, and the still limited knowledge require interdisciplinary research and modeling, for which we collaborate within the Cluster of Excellence SimTech.