Medical Research

Salk Institute for Biological Studies

Janelle Ayres
La Jolla, CA
$1,000,000
June 2018

Host-microbe interactions have traditionally been viewed as antagonistic, with most investigators focusing on understanding host resistance mechanisms that kill pathogens.  Salk researchers have been characterizing host-microbe interactions from a fundamentally distinct perspective—how do animals survive when interacting with microbes?  Health is traditionally believed to be a passive homeostatic state and disease occurs when there’s disruption in the system, such as the presence of a pathogen.  It would then follow that removal of the pathogen would return the system back to a healthy state.  However, in many scenarios, the collateral damage associated with pathogen elimination can do more harm than the pathogen itself, as is seen with sepsis and influenza infection.  Salk investigators hypothesize that maintaining health during infection is an active process, involving mechanisms that coordinate cooperative interactions between the host and pathogens.  This is based on Salk researchers’ discoveries of co-operative defenses that protect the host during infections by alleviating physiological damage without killing the pathogen.  The investigators plan to develop an approach to perform systems level analyses to elucidate the mechanisms contributing to co-operative defenses against two infections in the elderly: sepsis induced by intestinal perforation and influenza.  They will also identify novel methods to manipulate these defenses and strategies to determine how cooperative defense therapies influence pathogen virulence, evolution and attenuation. The project could generate a fundamentally different perspective on understanding and treating many infectious diseases.

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