Mapping the road to recovery - Does the way we get better differ from the way we

描述 摘要： 我假设从感染中恢复是一个积极的过程，与我们从健康中恢复的途径不同。 到病理学;我想了解是什么特性使病人对感染有抵抗力。换句话说， 我们会生病并康复吗？ 我的目标是修复我们在实验室中研究的微生物发病机制与我们在实验室中研究的方式之间的不和谐。 治疗感染的病人。作为研究感染的科学家，我们主要定义控制感染的机制， 宿主会有多恶心我们的哲学是，如果我们能防止人们变得极端， 伊利诺伊州不幸的是，这意味着我们很擅长定义病人的病情， 他们出现在急诊室;我们把它留给医生来清除感染，让病人恢复健康。 状态恢复健康的途径可能涉及与疾病途径相同的生理机制 但也有可能不会，我们不知道，因为我们不研究康复。 我提出了一个研究宿主-微生物相互作用的新范式，我们用整个动物来定义 控制恢复的属性（从疾病中恢复的路线）和恢复力（宿主的能力） 然后再回到原来的状态）。我将确定指导复苏的基本原则， 建立一个概念框架，在这个框架中，可以继续研究疾病的这一被忽视但重要的阶段。我 我将用以下三个目标来剖析这个问题。 目标1：测试已知的决定衰退的机制是否参与恢复。 将测试已知的耐药性和耐受性机制在细菌感染恢复中的作用。 这将有助于描述控制恢复曲线形状的属性。 目标2：确定参与恢复的新机制。 我们将进行正向遗传筛选，寻找从感染中恢复能力改变的突变体。这将 引导我们走向新的生物学，提出一个开放的问题，即恢复需要什么，而不是问 “恢复是否需要”进程X“？” 目标3：建立一个预测性的系统级复原力模型。 我们将使用数学模型来定义弹性系统，这些系统要么是健康的，要么是被持续感染所困 或促炎状态，然后使用前两个目标中开发的工具测试这些模型。

DESCRIPTION Abstract: 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 recovery rather than asking “is ‘process X’ required for recovery?” Aim 3: Develop a predictive systems-level model of resilience. We will use mathematical models to define resilient systems that are either healthy or stuck in persistent infections or pro-inflammatory states and then test these models using the tools developed in the first two aims.