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，不同于我们从健康到病理的路线;我想了解是什么特性使患者对感染有弹性。那么，我们是如何生病并康复的呢？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治疗感染患者的方式之间的不和谐。作为研究感染的科学家，我们主要是定义控制宿主生病程度的机制。哲学是，如果我们能防止人们患上重病，我们就能帮助他们。不幸的是，这意味着我们很擅长定义病人在急诊室出现时的病情;我们把清除感染和恢复病人健康状态的工作留给了医生。恢复健康的途径可能涉及定义疾病途径的相同生理机制，但也可能不是;我们不知道，因为我们不研究恢复。我提出了一个研究宿主-微生物相互作用的新范式，我们使用整个动物来定义控制恢复（从疾病中恢复的路径）和恢复力（宿主受到干扰然后恢复到原始状态的能力）的属性。我将确定指导康复的基本原则，并建立一个概念框架，以便在这个被忽视但重要的疾病阶段开展工作。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。这将通过提出一个开放性问题，即需要什么才能再生，

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 rec