Development of Cardiovascular Regulatory Mechanisms: Exploring the Early Embryonic Frontier II

项目概要-0614815该项目的长期目标是了解脊椎动物胚胎中生理过程的调节如何与发育过程结合在一起。重点是早期胚胎发育，这既没有得到充分的研究，也没有得到很好的理解。三个研究目标包括创新的鸟类模型胚胎心血管系统发育生理学实验，以及包括研究生和本科生与初中和高中教师及其学生合作的多方面研究培训。具体地说，本项目的目标是：1)确定早期胚胎心血管调节的发育。据推测，心脏内部机制(肌肉长度-张力关系)与血管自动调节(局部水平控制的血管的收缩和扩张)一起，必须负责对早期胚胎血压和血流的任何调节。为了验证这一假设，将在体内测量血容量负荷期间的血压和血流量，以及测量血管活性物质和氧气水平的影响，以确定发育调节的开始。。2)血容量调节的发展探索。第二个假设是，在神经和/或激素调节的心血管和肾脏机制充分发展之前，血容量最初的调节很差。鸟类胚胎中的液体平衡将通过血液隔室的加载和丢失而受到挑战。然后将测量血压、心率、红细胞数量、血管外水分运输和血容量，以确定发育开始的代偿机制。3)拓展教师生理学教育专业。国际数学研究所新设立的科学和数学高级研究技术(SMART)项目让极具积极性的高中教师接触到国际数学研究所实验室的当代研究。在与北大文理和教育科学教育学学院的密切合作下，这项计划将扩展到高中以外的地方，包括中学教师，并将使用更先进的评估工具来评估计划校友的表现改善(例如，改进的标准化学生考试成绩和学生预修课程入学)。智力优势：这些研究将在三个方面产生关键的科学贡献。1)关于脊椎动物胚胎如何生理发育的信息很少。这些测量将为早期胚胎心血管系统(CVS)的个体发育提供重要的、基于机械的信息，提高对心血管调节如何受到器官发生和胚胎生长过程中发育过程的影响并与之整合的理解。2)这些信息将有助于更好地解释CVS的表型可塑性，并有助于更好地理解“胎儿程序化”现象。3)在为人类胎儿甚至胚胎的先天性缺陷制定矫正程序之前，加强对脊椎动物胚胎生理学的了解是至关重要的。更广泛的社会影响：除了培养本科生、毕业生和博士后外，SMART项目还将初中生和高中生纳入其中，将研究和教育融为一体。SMART让理科学校的教师在北卡罗来纳大学的生理学实验室进行原创生理学研究。据推测，这些教师然后将他们的经验传授给他们的学生，增强他们对科学的热爱和迷恋。德克萨斯州不再拥有单一多数人口，这使得PI的实验室能够指导少数族裔的研究生和本科生(PI的实验室人员中有50%是由NSF鼓励的少数族裔组成的)。最后，将继续开发NSF支持的发育生理学社区网站，为特定的队列(例如本科生)创建资源部分。作为进一步的外展机制，将创建特定的网络材料，向公众说明为什么发育生理学是NSF重要的资助目标。总而言之，这一持续研究计划将增进对胚胎生理学的理解，对发育进化生物学产生新的见解，通过博士后研究员为本科生提供当代培训机会，并为在校学生创造发现机会。

PROJECT SUMMARY - 0614815The long-term goal of this program is to understand how regulation of physiological processes is integrated together with developmental processes in vertebrate embryos. Emphasis is on early embryonic development, which is both inadequately studied and poorly understood. Three research objectives integrate innovative developmental physiology experiments on the cardiovascular system of bird model embryos (chicken, emu) together with multi-faceted research training comprising graduate and undergraduate students collaborating with middle and high school teachers and their pupils. Specifically the aims of this project are:1) Determination of the Development of Early Embryonic Cardiovascular Regulation. It is hypothesized that intrinsic cardiac mechanisms (muscle length-tension relationships), in concert with vascular autoregulation (constriction and dilation of blood vessels controlled at the local level), must be responsible for any regulation of early embryonic blood pressure and flow. To test this hypothesis, in vivo measurements of blood pressures and flows will be made during blood volume loading, as well as measurements of the effects of vasoactive substances and oxygen levels, will be used to determine the developmental onset of regulation. . 2) Exploration of the Development of Blood Volume Regulation. As second hypothesis is that blood volume is initially poorly regulated until neurally and/or hormonally regulated cardiovascular and renal mechanisms develop sufficiently. Fluid balance in bird embryos will be challenged through blood compartment loading and loss. Blood pressure, heart rate, red blood cell numbers, water transport out of the vessels and blood volume will then be measured to determine the developmental onset of compensatory mechanisms. 3) Expansion of Teacher Physiology Education Program. The PI's newly established Science and Math Advanced Research Techniques (SMART) program exposes highly motivated high school teachers to contemporary research in the PI's lab. In close collaboration with UNT's science pedagogy faculty in Arts and Sciences and in Education, this program will be expanded beyond high school to include middle school teachers, and will use more advanced assessment tools for evaluating performance improvement in program alumni (e.g. improved standardized student test scores and student advance placement course enrollment).Intellectual Merit: Key scientific contributions will emerge from these studies in three areas. 1) Little information exists on how vertebrate embryos develop physiologically. These measurements will provide vital, mechanistically-based information on the ontogeny of the early embryonic cardiovascular system (CVS), improving understanding of how cardiovascular regulation is affected by, and integrated with, developmental processes during organogenesis and embryonic growth. 2) This information will enable better interpretation of CVS phenotypic plasticity and yield greater understanding of the phenomenon of "fetal programming". 3) Enhanced understanding of embryonic physiology in vertebrates is vital prior to creating corrective procedures for congenital defects in the human fetus and even embryos. Broader Societal Impact: In addition to training undergraduates, graduates and post-docs, the SMART Program integrates research and education by including middle as well as high school students. SMART engages science school teachers in original physiology research in UNT's physiology laboratories. It is hypothesized that these teachers then impart their experience to their students, enhancing a love and fascination for science. Texas no longer has a single majority population, enabling the PI's lab to mentor minority graduate and undergrad students (50% of the PI's lab personnel consist of minorities encouraged by NSF). Finally, development will continue for the NSF-supported Developmental Physiology community website by creating resource sections for specific cohorts (e.g. undergrads). As a further outreach mechanism, specific web material will be created to illustrat to the lay public why developmental physiology is an important NSF target for funding.In summary, this continuing research program will enhance understanding of embryonic physiology, yield new insights into developmental evolutionary biology, provide contemporary training opportunities for undergrads through post-doctoral fellows, and create discovery opportunities for school students.