Within the project different models shall be developed and documented, to those belong models of the wnt pathway. Different models shall be developed for different objectives and complex phenomena like the interaction between different pathways shall be explored. One focus of interest will be spatial processes. The concrete models will be developed in close cooperation with projects in FS I and FS II as it shall help evaluating the methods that are developed in these projects. Also this project will help to answer questions that are raised in projects in FS III. In addition, the different phases of the systems biology life cycle shall be analyzed and means that help a better integration between wet-lab and dry-lab experiments shall be developed, e.g., in the area of parameter estimation, or model validation.

The work is currently based on the modelling and simulation framework JAMES II, which is permanently extended to meet the challenges arising out of this project. Ongoing work is, e.g., the integration of further efficient algorithms and data structures for efficient simulations, the integration of sequential and parallel optimization algorithms for model parameter optimization, the integration of mechanisms for model validation, the integration of additional modelling languages to ease the creation of models, on reliable modelling and simulation experiments, on general flexible, scalable and reusable architectures for these, on automizing parts of the modelling and simulation workflow, workflows for modelling and simulation, and on quality issues in modelling and simulation software products.

Currently we are focusing on a better integration of technology for dry-lab experiments - a prerequisite for the integration of wet- and dry-lab technology.

Recent diploma/master thesis

• Arvid Schwecke (2007): Parameteroptimierung und Sensitivitätsanalyse in James II.  Diploma thesis, University of Rostock.
• Stefan Leye (2008): Grid-Inspired Simulation of Computationally Intensive Models.   Diploma thesis, University of Rostock.
• Sebastian Lieske (2008): Aggregation verteilter Simulationsdaten.   Diploma thesis, University of  Rostock.
• Peter Sievert (2008): Parallele Optimierung von Simulationsmodellen.  Diploma thesis, University  of Rostock.
• Yvonne Oertel (2009): ExML - ein Austauschformat für valide Experimentbeschreibungen zum Austausch zwischen verschiedenen Simulationssystemen.   Diploma thesis, University of Rostock.
• Alexander Steiniger (2009): Web-basiertes visuelles Monitoring von James II Simulationen.  Diploma thesis, University of Rostock.
• Enrico Seib (2010): Arbeitsabläufe in der Modellierung und Simulation. Masters thesis, University of  Rostock.
• Stein, Michael (2011): Integratiing LoLa into JAMES II. Bachelor thesis, University of Rostock
• Bartels, Simon (2011): The integration of software to compute BioPEPA models in JAMES II. Bachelor thesis, University of Rostock / University of Edinburgh

A postdoctoral research fellow in the field of biology, medicine or chemistry with excellent experience in molecular medicine will be employed. Additionally knowledge in creating models based on Wet-Lab data is demanded. The aim is to form an improved data base in particular regarding spatio-temporal processes in real time measurement for modelling and simulation. For this purpose new methods, like the use of Quantu Dots for labelling of proteins in living cells, are analysed and integrated in the GRK. Secondary the holder of position helds a central role in the monitoring of the data collection and summary as well as in the standardisation of processes. One of the tasks will be to write suitable SOPs (Standard Operating Procedures) for data collection, to provide identically qualified data sets for modelling.

This project will be in line with a multidisciplinary approach involving both wet-lab and dry-lab experimentation, to improve the understanding of wnt-modulated neuronal differentiation and to provide suitable data for computational modeling, respectively. The aim of this project will consist in the study of a potential cross-link between canonical wnt/β-catenin and non-canonical wnt/Ca²⁺ pathways. While numerous investigations are still under way to supplement knowledge of wnt-signaling pathways, studies are mainly focused on one pathway at a time. If we consider the cellular complexity, such pathways should clearly interact. However cross-talks between wnt pathways still remain unclear. A cross-talk between canonical wnt/β-catenin and non-canonical wnt/Ca²⁺ pathways will be investigated. Mainly wet-lab techniques will be used for the study of dynamic events occurring upstream from such pathways during wnt differentiation: Ca²⁺ release in cytosol, mitochondrial activity, H₂O₂ production and functioning as intracellular messengers, Dishevelled/Nucleoredoxin coupling, among others. Once this work like “piecing a jigsaw together”, quantitative data will be put together for dry-lab use.

Besides the visual analysis of large isolated data sources, the research within the Research Training Group increasingly involves large, heterogeneous data sets consisting of multiple data sources. It is the long-term aim of this project to develop approaches for visually exploring such heterogeneous information landscapes. The key for this lies in a graph-like data description, with the different data sources being the nodes and the implicit connections between data sources due to equivalence and foreign key relations being the edges. Additionally, equivalences can be determined from ontologies as it is not uncommon in the life sciences and also used in the subprojects "H1 - Defining and storing model components" and "H3_1 - Distributed information retrieval using web based nets". Assuming an explicitly modeled data description, the described information landscape can be seen as a data set on its own and thus visually explored. In the course of this project, such a data description as well as an interactive Representation for it shall be developed for the data sources within the Research Training Group as a stepping stone for later work.

The overall goal of this project is to better support biologists in conducting simulation experiments with JAMES II, the major modeling and simulation software used and developed in the graduate school. At first, biologists should be supported in designing experiments that are valid, efficient to compute, and yield meaningful results. These simulation experiments should be specified in a general format that fosters reuse and allows a prior analysis of experiment properties (e.g. regarding their structure).

Secondly, the experiments need to be executed by the most suitable combination of algorithms. This combination of algorithms should be selected automatically, since users are easily overwhelmed by the plethora of available algorithms.

Finally, the outcomes of simulation experiments have to be analyzed carefully, particularly regarding their validity. This motivates enhanced methods for experiment design (so that, e.g., model validity regarding certain aspects can be ascertained) and also additional support for the presentation of the experiment results.

Dependencies on other projects:

• The simulation experiments shall help to understand models of the biological systems of interest (e.g., multi-level models, stochastic models with continuous space, or mathematical models).
• The design and specification of experiments should base on the notion of modeling and simulation workflows.
• The execution of experiments by suitable algorithm combinations requires simulation algorithm selection, a methodology which needs further enhancements in this context (e.g., to provide automatic selection for other kinds of JAMES II algorithms).
• The output analysis (and parts of the experiment design) should incorporate methods for experimental model validation.

Current status:

• Familiarization with the concrete biological questions that could be answered by simulation experiments.
• Enhancing the support for result presentation in JAMES II.
• Investigating the automatic selection of auxiliary algorithms.