Redox homeostasis is central to the functions of oxygenic photosynthetic organisms such as cyanobacteria and plants. In this project, a systems approach will be undertaken to analyze the impact of cellular redox status on the overall functions of these organisms. The initial focus will be on the cyanobacterium Synechocystis 6803, with subsequent applications in the understanding of the biology of Arabidopsis, a vascular plant, and Physcomitrella, a non-vascular plant. Synechocystis 6803 has a completely sequenced genome and is amenable to high-throughput genome level manipulations. Although the detailed inventory of the genes, transcripts and proteins are available for Synechocystis, it is inadequate to comprehend the organizational hierarchy of the complex functions of this organism. A multidisciplinary approach will be used to resolve this gap in fundamental knowledge. The expertise of the project team spans molecular genetics, biochemistry, proteomics, metabolomics, computational biology and systems engineering, which includes nonlinear modeling, estimation and statistical analysis. The experimental research experience of the team spans model systems in cyanobacteria, moss and flowering plants. One aim is to infer a gene regulatory network in cyanobacteria that will include identification of the sensing and signaling pathways. In addition, a gene regulatory network will be independently generated in Arabidopsis, and the conservation of the genes and interactions will be evaluated. The network will be validated, the contribution of the network modules to the overall redox regulation will be studied, and the model will be extended to Physcomitrella. Such an iterative process is expected to generate fundamental insights into the organization and function of the redox control network (RCN) in these organisms. Furthermore, the proposed approach, viz. first to model an RCN in cyanobacteria and then to extend it to plants, will highlight the expected conserved nature of these processes during the evolution of land plants.
Broad Impact: The research activities in this project will be intimately connected to the training and development of undergraduate, graduate and post-doctoral students, and visiting scholars, both at Washington University and Colgate University. In particular, students from both Biology and Systems Engineering will become well-versed in the use of mathematics and computational methods to answer challenging questions in biology. Collaborative interactions with Saitama University will allow scientific interactions and research visits between USA and Japan. An important goal of this project is an integration of cutting-edge technologies with learning experiences that will inspire faculty and student development from small colleges lacking significant research programs. The students will obtain mentoring, research credit and training. They will become aware of the fascinating array of activities and career choices in modern life science research. Hands-on training in genomics, bioinformatics and systems science research will have far-reaching educational impacts well beyond the project period. The link for the project web site is www.sysbio.wustl.edu/.
