The Network Biology of Pathogen-Host Interactions Driving Exacerbation in Chronic Obstructive Pulmonary Disease (COPD)
Abstract
Chronic obstructive pulmonary disease (COPD) remains a poorly understood heterogeneous disease with many different bacteria and viruses, different triggers of inflammation, and changes in the control of immune response contributing to its onset and progression. Severe and often life-threatening complications arise when COPD sufferers contract infection, which for some is especially frequent and especially disabling. Traditional medical research looks for broken parts, that is, molecules or cells that in these illnesses are absent or too abundant, without paying much attention to how the parts fit together and whether or not the complete assembly is operating effectively. Despite significant scrutiny of the various bacteria and other organisms colonizing the respiratory tract, as well as the different molecules the immune system uses to communicate and fight infection in COPD sufferers, little progress has been made in disrupting the illness and reducing the frequency and severity of these infectious episodes. In this proposal, we hope to continue our exhaustive survey of microorganisms in the respiratory tract and the ongoing activation of the immune system in these individuals, but this time take our investigation further by attempting to pull the puzzle pieces together into a broad picture of the fundamental mechanisms that underlie COPD. In much the same way as pilots use simulators to understand the capabilities of their aircraft during flight training, our group has been using computer mockups at different levels of detail to imitate the dynamic behavior of the immune system. In this work, we will use computers to extract from large electronic libraries what researchers believe they understand about basic immune biology and combine this with data from broad surveys of the airway’s microscopic ecosystem and the molecules used by our own immune system. In this way, we will create focused computer mockups of COPD biology that mimic stable health and the response to infection in specific groups of individuals, allowing us to follow the flow of biological signals and determine where and when things go awry. This in essence will highlight which immune programs are inappropriately called in response to an infectious episode and which programs could be called to reduce vulnerability and support a more robust recovery.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Nov 19, 2019
- Source ID
- W81XWH1910805
Entities
People
- Sanjay Sethi
Organizations
- Buffalo VA Medical Center
- United States Army