I hypothesize that recovery from infection is an active process that differs from the route we take from health to pathology;I want to understand what properties make patients resilient to infections. In other words, how do we get sick AND recover? My goal is to repair the dissonance between microbial pathogenesis as we study it in the lab and the way we treat patients with infections. As scientists studying infections we mostly define the mechanisms controlling how sick a host gets. The philosophy is that we can help people if we can prevent them from getting extremely ill. Unfortunately, what this means is that we are great at defining just how sick a patient will be when they show up in the ER;we leave it to the physician to clear the infection and return the patient to a healthy state. The route back to health may involve the same physiological mechanisms that define the route to sickness but it may not;we don't know because we don't study recovery. I am proposing a new paradigm for studying host-microbe interactions where we use whole animals to define the properties governing recovery (the route back from sickness) and resilience (the ability of the host to be perturbed and then return to its original state). I will identify fundamental principles governing recovery and to establish a conceptual framework in which this neglected but important phase of disease can be pursued. I will use the following three aims to dissect this problem.
Aim 1 : Test if mechanisms known to dictate decline are involved in recovery. Known resistance and tolerance mechanisms will be tested for their role in recovering from bacterial infections. This will help describe the attributes that control the shape of a recovery curve.
Aim 2 : Identify novel mechanisms involved in recovery. We will perform a forward genetic screen for mutants with altered ability to recover from infections. This will lead us towards new biology by asking an open question about what is required for rec

Agency
National Institute of Health (NIH)
Institute
National Center for Complementary & Alternative Medicine (NCCAM)
Type
NIH Director’s Pioneer Award (NDPA) (DP1)
Project #
8DP1AT007753-02
Application #
8331607
Study Section
Special Emphasis Panel (ZGM1-NDPA-A (01))
Program Officer
Pontzer, Carol H
Project Start
2011-09-30
Project End
2016-07-31
Budget Start
2012-08-01
Budget End
2013-07-31
Support Year
2
Fiscal Year
2012
Total Cost
$790,000
Indirect Cost
$290,000
Name
Stanford University
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305