Systems biology approach for analysis of transcriptional regulation: Hox-gene circuits in cancer
Consortium leader: Professor OLLI KALLIONIEMI
Medical Biotechnology Department, VTT Biotechnology and University of Turku
Other project leaders of the consortium:
Jaakko Astola, professor, Institute of Signal Processing, Tampere University of Technology
Outi Monni, Biomedicum Chip Center, University of Helsinki
Doctoral students of the consortium:
Sami Kilpinen, VTT Medical Biotrechnology and University of Turku, Biomedicum Biochip Center and University of Helsinki
Rami Mäkelä, VTT Medical Biotechnology and University of Turku
Reija Autio, Institute of Signal Processing, Tampere University of Technology
Other researchers of the consortium:
Sampsa Hautaniemi, Institute of Signal Processing, Tampere University of Technology
Key words: cancer, molecular oncology, algorithms, gene amplification, drug targets, RNAi, gene regulation
Project desciption and main results:
Our aim is to develop integrated laboratory methods and dynamic algorithms for systems biological studies of gene regulatory circuits. We will test and apply these methods and strategies to build a model of the HOXB7 mediated transcriptional modulation and subsequent signaling pathways in normal and cancer cells.
In the first phase, database searches will be accomplished to gather information about the role of HOXB7 in various tissues and cell lines. In the second phase, downstream transcriptional signaling network for HOXB7 will be studied by utilizing RNAi and gene expression microarray technologies. In the subsequent phases of the proposal, we will explore the significance of HOXB7 and related HOX gene circuits in cancer and during drug perturbations. We will also develop cell lysate-based immunoprofiling methods to identify HOX-gene mediated signaling changes at the protein level and their association with cell biological phenotypic endpoints. Algorithm development will be a key component of the program, and will be integrated in all the phases of the study, especially in experimental design, data analysis, model building and re-design of new experiments. Algorithm development will include Bayesian networks, IC algorithms, difference-based regulation finding methods, probabilistic Boolean networks and many other state-of-the-art and newly-developed systems biology tools.
Our overall goal is to construct graphical illustrations and dynamic mathematical models that explain information processing through HOXB7 mediated pathways in human breast cancer cells. We will also develop laboratory methods and new algorithms for systems biology studies of any gene regulatory circuits. In addition to the technical and informatic advances, we expect that these results will lead to an improved understanding and ability to therapeutically exploit the deregulation of the HOX-gene circuits in cancer.
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