Signaling pathways and gene regulatory networks leading to generation of a lymphocyte phenotype pathogenic in asthma and allergy
Consortium leader: professor RIITTA LAHESMAA
Turku Centre for Biotechnology, University of Turku
Other project leaders of the consortium:
Timo Koski, professor, Department of Mathematics, Linköping University, Sweden,
Tero Aittokallio, Department of Mathematics and Turku Centre for Biotechnology
Matej Oresic, Turku Centre for Biotechnology and VTT Biotechnology
Doctoral students of the consortium:
Mikko Katajamaa, Turku Centre for Biotechnology
Tapio Lönnberg, Turku Centre for Biotechnology
Ilana Saarikko, Department of Mathematics and Turku Centre for Biotechnology
Laura Elo, Department of Mathematics and Turku Centre for Biotechnology
Johanna Tahvanainen, Turku Centre for Biotechnology
Soile Tuomela, Turku Centre for Biotechnology
Other persons involved in the project:
Key words: lymphocytes, cell signaling, cytokines, inflammatory diseases, functional genomics, SNP, bioinformatics
Project desciption and main results:
This project aims at creating an integrated data platform, which is used to model signaling pathways and gene regulatory networks critical for the development of a Th2 lymphocyte phenotype pathogenic in asthma and allergy. The starting point for the studies is the transcriptomics, proteomics and cell signalling protein complex data. We have already systemically characterized the early stages of Th2 lymphocyte differentiation.
Clarification of the pathways leading to the development of functionally distinct lymphocyte subsets is crucial for understanding the pathogenesis of immune mediated diseases and provides basis for better strategies in developing diagnostics and therapies for these diseases.
Simulation studies and mathematical modelling will be carried out to predict the pathways and regulatory networks and to construct signalling pathways likely to be most relevant for the lymphocyte subset development. The theoretical predictions will be tested experimentally by interfering with the particular pathways specifically using gene silencing (siRNA) and gene overexpression. In addition, novel proteomics methods will be developed that will enable us to detect and quantify protein modification and variants. The experimental data obtained is introduced back to the integrated data platform and the model is adjusted accordingly. This iterative modelling and experimental process is the key for the program.
Our truly cross-disciplinary project meets and exceeds the key criteria spelled out in the SysBio program description. The project is composed of three subprojects that can be succesfully completed only by intensive collaboration between the three participating groups. The study is based on integrating the data obtained systematically by functional genomics and proteomics and building a mathematical model of early signals and gene regulatory networks determining the faith of a precursor cell and needed to initiate lymphocyte differentiation process.
The results of modelling work will lead to hypotheses that will be tested experimentally. Molecular genetics will be applied to determine the importance of findings on the development of human asthma and allergy. To achieve the goals we will combine expertise of researchers representing multiple disciplines with bioinformatics having a central integrating role. The project provides an opportunity for six Ph.D. students partly co-supervised by the group leaders of the consortium.
Publications: