2011 Mechanisms of Membrane Transport Gordon Research Conference

描述(申请人提供)：我们的目标是组织和促进戈登研究会议，该会议将成为多学科讨论的跳板，讨论与膜运输过程及其调控的机械理解相关的想法和技术。对于这样的会议来说，这是一个特别合适的时刻。最近从模式生物中获得膜蛋白的高分辨率结构的成功启发了该领域，并鼓励了新一代研究人员的进入。尽管新的结构继续以快速的速度出现，但功能分析正在这些结构的背景下重生；由转运体结构指导的机械分析正在改变我们的领域。机制包括运输者或渠道的详细结构和动态行为；会议的广泛和长期目标是通过将静态结构的见解与动态功能分析的见解紧密结合来理解机制。了解基本的转运蛋白机制是了解它们的生理功能、调节以及它们在疾病中的破坏的关键一步。因此，“膜转运机制”GRC的具体目标是利用将形式与功能联系起来的前所未有的机会，并鼓励年轻研究人员--主要是受过物理和生物物理科学培训的--与在生理学、细胞生物学和生物化学等领域有经验的更成熟的研究人员之间进行富有成效的互动。这种对话在其他情况下很难进行，但对初级调查人员的专业发展至关重要，并为更资深的科学家注入活力。这需要我们的会议强调最相关的最新调查结果，我们需要招募有前途的年轻科学家以及更有经验的调查人员。这一双重使命一直是我们选择演讲者和组织该计划的指导标准。适当的财政支助对于招聘有前途的年轻研究人员和确保博士后研究员和研究生有足够的代表性至关重要，尤其重要。这批人很快就会在这一领域处于领先地位，我们必须为他们提供足够的财政支持，以参加将对他们的未来产生重大影响的会议。这项工作与人类健康高度相关：转运体和通道是肾脏调节血清离子水平、肠道吸收营养物质和神经元调节信号的关键因素，以及许多其他过程。了解这些蛋白质的基本机制将有助于更好地了解正常功能，以及高血压、吸收不良综合征和囊性纤维化等疾病，并开发新的和改进的治疗药物。 与公共健康相关：通过调节离子和营养素等水溶性底物的运动，转运体和通道在肾脏和消化系统中都发挥着重要作用。一些被称为离子通道的转运蛋白主要是通过移动K+、Ca~(2+)或Cl-等离子来传递电信号，而另一些转运蛋白，如转运蛋白和泵，则同时参与信号和营养物质的获取/清除。转运体和通道协同作用，是肾脏调节血清离子浓度的核心元素，而血清离子浓度又对调节血液的压力和成分至关重要：肾脏中关键的转运体和通道的功能障碍直接导致血压紊乱，包括巴特综合征和其他疾病。在肠道中，转运体允许有选择地将营养吸收到血液中；这些转运体的功能障碍会导致吸收不良综合征。相反，当转运蛋白功能得到仔细调节时，疾病往往可以被治愈或控制，就像今天临床上使用的各种药物(利尿剂、抗高血压药、抗抑郁药等)一样。为了有效地了解和治疗膜转运功能疾病，我们必须了解这些转运蛋白是如何在分子水平上发挥作用的。推进这一理解是“膜运输机制”戈登研究会议的目标，这次会议聚集了一些研究运输蛋白质的顶尖科学家，介绍和比较结果，讨论新的想法，并建立合作。

DESCRIPTION (provided by applicant): Our objective is to organize and promote a Gordon Research Conference that will be a springboard for multidisciplinary discussion of ideas and technologies related to a mechanistic understanding of membrane transport processes and their regulation. This is a particularly opportune moment for such a meeting. Recent success in obtaining high-resolution structures of membrane proteins from model organisms has inspired the field and encouraged entry of a new generation of investigators. Though new structures continue to emerge at a rapid pace, functional analysis is having a rebirth in the context of these structures; mechanistic analyses guided by transporter structures are transforming our field. Mechanism encompasses both the detailed structure and the dynamic behavior of a transporter or channel; the broad and long term goal of the conference is to understand mechanism by tightly integrating insights from static structures with those from dynamic functional analyses. Understanding fundamental transporter mechanisms is a key step to understanding their physiological functions, their regulation, and their disruption in disease. Accordingly, the specific aims of "Mechanisms of membrane transport" GRC are to take advantage of the unprecedented opportunity to link form with function and encourage productive interactions between young investigators - largely trained in the physical and biophysical sciences - and more established investigators whose experience is in areas such as physiology, cell biology and biochemistry. Such dialogue occurs with difficulty in other settings, but is essential to the professional development of junior investigators and invigorates the portfolio of more senior scientists. This requires that our Conference emphasize the most relevant recent findings, and that we recruit promising young scientists as well as more seasoned investigators. This dual mission has been a guiding criterion in our selection of speakers and our organization of the program. Adequate financial support is essential and especially important for recruiting promising young investigators and ensuring adequate representation of postdoctoral fellows and graduate students. This cohort will soon be leading the field, and we must provide them sufficient financial support to attend a conference that will have a striking impact on their future. This work highly related to human health: transporters and channels are key elements in renal regulation of serum ion levels, intestinal absorption of nutrients, and neuronal modulation of signaling, among a host of other processes. Understanding the fundamental mechanisms of these proteins will lead to better understanding of normal function, of diseases like hypertension, malabsorption syndromes, and cystic fibrosis, and to development of new and improved therapeutic agents. PUBLIC HEALTH RELEVANCE: By regulating the movement of water soluble substrates such as ions and nutrients, transporters and channels play essential roles in both the kidney and digestive systems. Some transport proteins, called ion channels, exist primarily to send electrical signals by moving ions like K+, Ca2+, or Cl- across the membrane, whereas others, such as transporters and pumps, are involved in both signaling and nutrient access/removal. Transporters and channels act in concert as the core elements of the kidney's machinery to regulate serum ion concentrations, which in turn is essential for regulating blood's pressure and composition: dysfunction of key transporters and channels in the kidney leads directly to disorders of blood pressure, including Bartter's syndrome and other diseases. In the gut, transporters allow the selective uptake of nutrients into the bloodstream; dysfunction of these leads to malabsorption syndromes. Conversely, diseases can often be cured or controlled when transporter function is carefully modulated, as by a wide range of drugs in clinical use today (diuretics, antihypertensives, antidepressants and many others). To effectively understand and cure diseases of membrane transport function, we must understand how these transport proteins operate at the molecular level. Advancing this understanding is the goal of the "Mechanisms of Membrane Transport" Gordon Research Conference, which brings together some of the foremost scientists studying transport proteins to present and compare results, discuss new ideas, and establish collaborations.