T1 TRANSLATIONAL

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 公共卫生官员面临的一个主要挑战是预测疾病的爆发。人畜共患疾病是一个特殊的挑战，因为对宿主转换背后的具体机制知之甚少。例如，哪些非生物因素增加了宿主转换的可能性？拟议的研究是一项跨学科的调查，将提供深入了解病毒宿主转换背后的机制。我们的中心假设，这是基于初步的 我们目前的研究结果是，病毒对温度小幅升高的适应增强了衣壳的稳定性，这反过来又增加了病毒宿主转换的可能性。我们感兴趣的是几度的温度差异，例如哺乳动物和鸟类之间的体温差异，或者由于全球变暖而可能在世界部分地区发生的变化。这是一项高度跨学科的研究，汇集了计算生物物理学家、进化生物学家和统计学家，对可能对人类健康产生重大影响的假设进行多管齐下的攻击。我们将通过以下具体目标来检验我们的中心假设：（i）使用实验进化来检验这样的假设，即携带适应性突变的病毒比野生型病毒更有可能转换宿主。(ii)使用生物物理模型来测试假设， 参与病毒宿主转换的突变增加了衣壳的稳定性。(iii)使用统计和空间建模来探索宿主转换的概率和空间异构环境中的传播动态。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. A major challenge for public health officials is predicting the outbreak of diseases. Zoonotic diseases are a particular challenge since little is known about the specific mechanisms behind host switching. For example, what abiotic factors increase the probability of host switching? The proposed research is an interdisciplinary investigation that will provide insight into the mechanisms behind viral host switching. Our central hypothesis, which is based on preliminary results from our current research, is that viral adaptation to small increases in temperature enhances capsid stability, which in turn increases the likelihood of viral host switching. We are interested in differences in temperature of a few degrees, such as the difference between mammalian and avian body temperature, or the change that might occur in parts of the world due to global warming. This is a highly interdisciplinary study that brings together a computational biophysicist, an evolutionary biologist and a statistician for a multipronged attack on a hypothesis that could have major implications for human health. We will test our central hypothesis via the following specific aims: (i) Use experimental evolution to test the hypothesis that viruses carrying adaptive mutations for increased temperature are more likely to switch hosts than the wild type viruses. (ii) Use biophysical modeling to test the hypothesis that some mutations involved in viral host switching increase the stability of the capsid. (iii) Use statistical and spatial modeling to explore the probability of host switching and the dynamics of spread in a spatially heterogeneous environment.