2012 Thiol-based Redox Regulation & Signaling GRC and GRS

描述(由申请人提供) 该提案请求支持将于2012年7月28日至8月3日在缅因州刘易斯顿的贝茨学院举行的关于基于硫醇的氧化还原调节和信号的第四次戈登研究会议(以及第一次相关的戈登研究研讨会)。这次会议的副标题“氧化还原调节和氧化应激的分子基础”反映了即将到来的会议的重点，即通过硫醇上的氧化还原修饰调节蛋白质功能和基本细胞过程之间的相互作用，以及在加剧氧化应激的环境条件下随之而来的调节失调。含有硫醇的蛋白质是细胞内主要的抗氧化剂，磷酸酶、激酶和转录因子中的硫醇的可逆氧化将硫醇氧化还原化学与基于磷酸化的信号转导、细胞增殖、细胞凋亡、基因调控、细胞周期控制等过程和途径联系在一起。以硫醇为基础的氧化还原动态平衡的失调，例如通过暴露于促进产生过度破坏性的活性氧物种的环境因素，可能会使氧化还原调节具有不可逆性，并对癌症和复杂的年龄相关疾病的发生和发展具有重大影响。这次跨学科会议是继在美国(2006年)和意大利(2008年和2010年)举行的三次非常成功的会议之后的第四次会议，将像过去一样，为从事该领域各个方面工作的分子生物学家和毒物学家、化学家和临床医生之间提供一个自由交流思想和方法的重要场所。虽然会议的主题领域是广泛的，但它与环境应激、癌症发生以及正常人类生理和疾病的分子基础的相关性是巨大的。通过将在生物物理方法、生物信息学和动物模型系统方面具有不同专业知识的研究人员与专注于疾病过程的临床研究人员和医生聚集在一起，会议预计将进一步促进合作并促进科学进步，前几次会议的成功就是例证。 公共卫生相关性：许多细胞功能依赖于涉及细胞内特定分子氧化还原性质变化的过程，而这些过程的失调是衰老和癌症发生和发展的主要组成部分。一种氨基酸，半胱氨酸(它包含一个硫醇基团)，起着分子开关的作用，是这些氧化还原变化的中心，尽管人们很少知道在正常和病理过程中发生氧化还原变化的分子细节。这次会议聚集了化学家、分子生物学家、毒理学家和临床医生，以促进对硫醇依赖过程的不同程度的理解的共享，并使我们能够从更好的理解中获得治疗益处。

DESCRIPTION (provided by applicant) This proposal requests support for the Fourth Gordon Research Conference (and first associated Gordon Research Seminar) on Thiol-based Redox Regulation and signaling to be held at Bates College in Lewiston, Maine, from July 28th to August 3rd, 2012. The subtitle of this conference, "Molecular Underpinnings of Redox Regulation and Oxidative Stress," reflects the focus of the upcoming meeting on the interplay between regulation of protein function and fundamental cellular processes through redox modifications on thiols, and the dysregulation that ensues under environmental conditions that exacerbate oxidative stress. Thiol-containing proteins are major antioxidants in cells, and reversible oxidation of thiols in phosphatases, kinases and transcription factors links thiol-based redox chemistry to phosphorylation-based signaling, cell proliferation, apoptosis, gene regulation, cell cycle control and other processes and pathways. Dysregulation of thiol-based redox homeostasis, for example by exposure to environmental agents which promote the generation of excessive damaging reactive oxygen species, may impart an element of irreversibility to redox regulation and has major implications for the onset and progression of cancer and complex age-related diseases. This interdisciplinary conference is in its fourth cycle after three very successful meetings in the U.S. (2006) and Italy (2008 and 2010), and will provide, as it has in the past, an important venue for the free exchange of ideas and methodologies among the molecular biologists and toxicologists, chemists and clinicians working on various aspects of the field. While the thematic area of the conference is broad-based, its relevance to environmental stress, carcinogenesis and the molecular basis for normal human physiology and disease is enormous. By bringing together investigators with varied expertise in biophysical methods, bioinformatics and animal model systems, with clinical researchers and physicians focused on disease processes, the meeting is expected to further stimulate collaborations and catalyze scientific progress as has been exemplified by the successes of the previous meetings. Public Health Relevance: Many cellular functions rely on processes that involve changes in redox properties of particular molecules within the cell, and the dysregulation of these processes is a major component of the onset and progression of aging and cancer. One amino acid, cysteine (which contains a thiol group), serves as a molecular switch and is central to these redox changes, although very few molecular details of which redox changes occur during normal and pathological processes are known. This conference brings together chemists, molecular biologists and toxicologists, and clinicians to promote the sharing of different levels of understanding of thiol-dependent processes and enable therapeutic benefits to be gained from our improved understanding.