PGA Project Summary

Genomic Analysis Of Stress and Inflammation

This PGA is centered at the Massachusetts General Hospital, Harvard Medical School, with bioinformatics participation from the Boston University Biomedical Engineering Department and the Genetics Department at Harvard Medical School. The investigators in the program propose to identify and characterize gene networks activated by pro-inflammatory, metabolic, and pathogen stresses affecting the cardiovascular system and the lung. Stress-activated pathways play central roles in the pathophysiology of some of the most important diseases addressed by the National Heart, Lung and Blood Institute (NHLBI), including atherosclerosis, pulmonary infection, cystic fibrosis, and heart failure. The exploration of these pathways is likely to result in the generation of fundamentally new insights into these disorders.

The various biological questions to be addressed in this work represent broad themes in biology, involving cellular interactions with the environment, signal transduction pathways, and regulation of gene expression. Two intersecting levels of collaboration will unify this work. On one level are the biological questions that each Principal Investigator (PI) is proposing to address, with the intellectual and material assistance of other investigators working in the program. The research projects are interrelated to produce synergies among research teams as well as among component technologies.

The research projects are entitled:

1. Genetic Dissection of Signal Transduction
2. Host-Pathogen Interactions: Pseudomonas and Cystic Fibrosis
3. Definition of Protein Networks using RNA Display
4. Macrophage Activation by Metabolic and Pathogen Stresses Disorders

On the second level are the biological and technological competencies resident within each component and to which all investigators have access. As each PI for a biological project is also a PI of one of the component services, the overall PGA has an unusually high level of collaboration built into the proposed science.

There are five Component Centers in the project:

1. Microarray and Sequencing Center
2. Education and Training Center
3. Proteomics and Molecular Biology Center
4. Human Tissue and Animal Model Center
5. Bioinformatics Center

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