Independent Scientist Development Award in Oxidative Stress and Apnea

描述(申请人提供)：Ortiz，Rudy M.K02：独立科学家奖摘要候选人。鲁迪·M·奥尔蒂斯博士是加州大学默塞德分校的生理学和营养学助理教授，这是加州大学系统的第10个也是最新的校园，也是21世纪第一个主要研究机构。我于2005年加入UCM，作为其创始教员之一，是其第一位西班牙裔教员，最近(02/09)成为UCM第一位被授予R01(来自NHLBI)的助理教授。家长基金使用北象海豹作为评估一些哺乳动物进化的生理和细胞机制的模型，这些机制使它们能够自然地适应极端环境条件，如长期禁食和呼吸暂停(睡眠和潜水引起的呼吸暂停)，这些可能会促进氧化应激及其相关病理。这些情况本来对人类是有害的，最终是致命的。目标。这一奖项将使我能够进一步扩大我的研究计划，利用受保护的时间来学习和融入我们以前在实验室中从未使用过的技术和技能，如qRT-PCR和高级层析。虽然我们已经开始探索这些技术，但受保护的时间将使我有更多的时间将这些技术作为稳定和常规的方法在实验室中实现。这将扩大我们的能力，提高我们科学的整体素质。改进我们的科学最终将提高我们的生产力，从而极大地增加我获得终身教职的机会，这是我相对近期(在未来1-2年内)的目标。最终，我的目标是在接下来的2-3年内，在我余下的职业生涯中，以多个同时获得R级奖项的形式获得足够的研究支持。这一资金水平应该足以支持一个研究小组至少10名成员，能够每年发表4-5篇论文。一旦我在实验室中完全确立了我的研究事业和必要的技能和技术，我打算在继续我的生物医学研究的同时，为代表不足的少数族裔开发和指导外部资助的培训计划(如MHIRT、MBR和MARC)。我认为自己是这些项目的产物，从我在德克萨斯A&M读本科开始就参与了这些项目，目前我参加了UCSC-MHIRT项目，这让我在这些项目方面有了丰富的经验。环境我的实验室和我的合作者的实验室(在家长R01拨款中提到)拥有实现拟议研究的科学目标所需的所有空间和设备。我有三位资深同事与我合作，就父母助学金与我定期会面，讨论助学金的进展情况。反过来，他们提供延长的导师和研究指导，以帮助确保我断奶后完全独立于研究。受保护的时间也将加强对我的学生的培训，我将能够投入更多的时间来监督他们的研究，这是由家长资助的。研究。这个新提出的特定目标的目的是评估嘌呤循环和HIF-1激活在北象海豹对睡眠呼吸暂停诱导的缺氧的自然耐受性中的贡献。这一特定的目标将解决的假设是，象海豹通过回收睡眠呼吸暂停诱导的缺氧所产生的嘌呤核苷来避免潜在的自由基产生，以及HIF-1在睡眠呼吸暂停期间被氧化还原依赖的机制激活，以协调细胞对缺氧的动态平衡反应。 公共卫生相关性：Ortiz，Rudy M.K02：独立科学家奖项目旁白象海豹除了慢性睡眠呼吸暂停导致的低氧外，还会经历长时间的食物和水缺乏，这两种情况都会迅速引起人类的心血管和呼吸系统并发症。然而，这些海豹必须进化出独特的强大的生理和细胞机制，以对抗通常与这些行为相关的潜在有害后果。阐明海豹体内的这些机制可能会揭示新的治疗靶点，以帮助缓解人类的这些后果。拟议的研究为将北象海豹发展为一个可行的生物医学模型提供了初步步骤，以研究为对抗氧化应激和炎症事件而进化的自然适应，这些自然适应通常是由长期食物剥夺以及睡眠和潜水相关的低氧引起的。

DESCRIPTION (provided by applicant): Ortiz, Rudy M. K02: Independent Scientist Award Abstract Candidate. Dr. Rudy M. Ortiz is an assistant professor of physiology and nutrition at the University of California, Merced, which is the 10th and newest campus of the University of California system and is the first major research institution of the 21st century. I joined UCM as a member of its founding faculty in 2005, was its first Hispanic faculty member, and recently (02/09) became the first assistant professor at UCM to be awarded an R01 (from NHLBI). The parent grant uses the northern elephant seal as a model for evaluating the physiological and cellular mechanisms some mammals have evolved that have allowed them to naturally adapt to extreme environmental conditions such as prolonged fasting and apnea (both sleep- and diving- induced) that may promote oxidative stress and its related pathologies. These are conditions that would otherwise be detrimental and eventually fatal in humans. Goals. This award will allow me to expand my research program further by using the protected time to learn and incorporate technologies and skills that we have not used previously in the lab such as qRT-PCR and advanced chromatography. While we have begun to explore these techniques, the protected time will allow me to focus more time on getting these techniques implemented as stable and routine methodologies in the lab. This will expand our capabilities and improve the overall quality of our science. Improving our science will ultimately increase our productivity and thus greatly enhance my chances of obtaining tenure, which is my relatively near-term (within the next 1-2 yrs) goal. Ultimately, my goal within the next 2-3 years is to have sufficient research support in the form of multiple and concurrent R-level awards for the remainder of my career. This level of funding should be sufficient to support a research team at least 10 members that is capable of producing 4-5 papers per year. Once I have fully established my research career and the requisite skills and techniques in my lab, I intend to develop and direct extramurally-funded training programs (such as MHIRT, MBRS and MARC) for underrepresented minorities as I continue my biomedical research. I consider my self a product of these programs having been involved with them since I was an undergraduate at Texas A&M and I currently participate in the UCSC-MHIRT program, which has given me extensive experience with such programs. Environment. My lab and that of my collaborators (mentioned in parent R01 grant) have all the space and equipment to required to accomplish the scientific goals of the proposed studies. I have 3 senior colleagues collaborating with me on the parent grant that I meet with regularly to discuss the progress of the grant. In turn, they provide extended mentorship and research direction to help insure my weaning to full research independence. The protected time will also enhance the training of my students I will be able to commit more time to supervising their research that is supported by the parent grant. Research. The goal of this newly proposed specific aim is to evaluate the contributions of purine recycling and HIF-1 activation to the northern elephant seal's natural tolerance against sleep apnea-induced hypoxia. This specific aim will address the hypothesis that elephant seals avoid potential free radical production by recycling purine nucleosides derived from sleep apnea- induced hypoxia, and that HIF-1 is activated by redox-dependent mechanisms during sleep apnea in order to coordinate the cellular homeostatic response against hypoxia. PUBLIC HEALTH RELEVANCE: Ortiz, Rudy M. K02: Independent Scientist Award Project Narative Elephant seals experience prolonged periods of food and water deprivation in addition to chronic sleep apnea-induced hypoxia, both of which can rapidly evoke cardiovascular and respiratory complications in humans. However, these seals must have evolved uniquely robust physiological and cellular mechanisms to counter the potentially detrimental consequences commonly associated with these behaviors. Elucidation of these mechanisms in seals may reveal novel therapeutic targets to help alleviate these consequences in humans. The proposed studies provide the initial steps towards developing the northern elephant seal as a viable biomedical model to study the natural adaptations evolved to counter oxidative stress and inflammatory events commonly induced by prolonged food deprivation and, sleep- and diving-associated hypoxia.