A new perspective for treating disease. There is a disconnect between our methods for treating diseases and our understanding of the mechanisms that keep us healthy; this needs to change. The past fifty years of biological research have done an excellent job of understanding disease pathogenesis by reducing the organism to its component parts, in order to understand the intricate details of how dysfunction of these parts leads to disease. A significant limitation to this approach, however, is that physiologies do not exist in isolation; when one system becomes dysfunctional, the whole body is affected. A second issue that complicates this approach is that current methods for treating disease primarily involve blocking pathogenic responses rather than inducing pathways that work to maintain health. The reason for this is two-fold: 1) scientists study disease, not health, and therefore do not understand the mechanisms that promote health; and 2) It is commonly assumed that blocking a pathogenic response will bring the patient back to a healthy state, which is not necessarily true. Therefore, rather than asking how we should treat disease, the question that should be asked is, ?How is health maintained?? To understand and ultimately manipulate the complex multi-directional interactions that occur between all of our physiologies, a novel approach is proposed in this application. This approach is based on understanding that the body and its resident microbiota have co-evolved to rely on communication between all physiologies in order to maintain proper physiological function. The overall hypothesis of this proposal is that health is an active process that includes the induction of physiological mechanisms coordinated by microbes. By understanding the physiological mechanisms our bodies encode and how microbes coordinate these processes to maintain health, treatments that work to extend health-span and lifespan by overriding physiological decline can be developed, enabling patients to stay healthy despite infection. This application proposes a new paradigm for studying disease, where whole animal models, evolutionary principles and host- microbe interactions are used to define the properties and fundamental principles governing health. The work resulting from this application will establish a new conceptual framework and approaches in which to mechanistically understand what it means to be healthy and how this can be applied to treat diseases.

Public Health Relevance

In this project, we will investigate the interactions between the host, infectious diseases and the intestinal microbiota and determine the mechanisms that enable a host to stay healthy during disease. We have developed a novel technique using whole animal models to enable us to systematically identify physiological mechanisms that work to maintain and induce health in the host. Our work will lead to novel therapeutic strategies to treat infectious diseases and beyond. !

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
NIH Director’s Pioneer Award (NDPA) (DP1)
Project #
5DP1AI144249-03
Application #
9977129
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Rothermel, Annette L
Project Start
2018-09-30
Project End
2023-07-31
Budget Start
2020-08-01
Budget End
2021-07-31
Support Year
3
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Salk Institute for Biological Studies
Department
Type
DUNS #
078731668
City
La Jolla
State
CA
Country
United States
Zip Code
92037