Research Starter Grant: Functional Characterization of MEL-28 in the Animal Model Caenorhabditis Elegans

细胞分裂可以说是发育过程中最具活力的事件。多个亚细胞过程必须协调，以确保正确分离细胞物质和胞质分裂的成功完成。例如，核被膜在S期是完整的，确保DNA复制的正确完成，当染色体在中期板对齐时，核被膜完全分解。这种分解是必要的，以便纺锤体微管可以接触浓缩的染色体并将它们拉到适当的极点。关于核膜的形成和破裂如何与DNA复制和染色体分离协调，人们知之甚少。了解染色质维持和核膜动力学之间的关系将揭示一般原则，从而管理细胞分裂过程中发生的多个并发事件。费尔南德斯博士发现了一种新的AT钩结构域蛋白，称为MEL-28（脊椎动物中的ELYS），它是核膜功能和染色质形态和运动的适当调节所必需的。本项目将对MEL-28进行功能研究，以更好地了解该蛋白如何协调两个不同的过程。智力优势：同时进行的亚细胞过程的协调是成功完成细胞分裂的关键，因此更好地了解这是如何完成的对于理解细胞如何分裂至关重要。费尔南德斯博士已经证明，MEL-28是核被膜结构和功能完整性以及染色质正确形态、凝聚状态和定位所必需的。然而，由于MEL-28是一种具有很少保守结构域的大蛋白，因此MEL-28蛋白如何发挥功能以完成这些任务在很大程度上仍然是未知的。因此，这项工作将导致理解一个重要的但新的蛋白质如何在其细胞分裂的基本作用中发挥作用。更广泛的影响：了解我们的自然世界的基础不仅仅是了解它的事实，而是了解这些事实来自哪里。让学生了解科学方法的最好方法是花时间在研究环境中作为积极的参与者。费尔菲尔德大学的本科生将执行本提案中描述的实验，从这些实验中收集经验数据，并解释这些数据，以确定它们是否支持或反驳我们的假设。对于许多学生来说，这将使他们第一次接触到原创研究。培养学生以这种方式从事研究将使他们成为更好的科学家。更重要的是，这些活动将帮助学生发展成为更好的思想家，从而使公民更有能力就如何管理我们的社会作出深思熟虑的决定。

Cell division is arguably the most dynamic event to occur during development. Multiple subcellular processes must be coordinated in order to ensure the correct segregation of cellular materials and the successful completion of cytokinesis. For instance, the nuclear envelope, which is intact during S-phase ensuring the proper completion of DNA replication, breaks down completely by the time the chromosomes are aligned at the metaphase plate. This breakdown is essential in order that the spindle microtubules may contact the condensed chromosomes and pull these to their appropriate poles. Very little is understood about how the formation and breakdown of the nuclear envelope is coordinated with DNA replication and chromosome segregation. Understanding the relationship between chromatin maintenance and nuclear envelope dynamics will reveal general principles whereby the multiple concurrent events that occur during cell division are managed. Dr. Fernandez has identified a novel AT-hook domain protein called MEL-28 (ELYS in vertebrates) that is required for both nuclear envelope function and the proper regulation of chromatin morphology and movement. This project will perform functional studies of MEL-28 in order to better understand how this protein coordinates two distinct processes.Intellectual Merit: The coordination of simultaneous subcellular processes is key to the successful completion of cell division, thus understanding better how this is accomplished is essential to understanding how cells divide. Dr. Fernandez has shown that MEL-28 is required for the structural and functional integrity of the nuclear envelope and for the proper morphology, condensation state, and positioning of the chromatin. However, as MEL-28 is a large protein with few conserved domains, it is still largely unknown how the MEL-28 protein functions to accomplish these tasks. Thus this work will lead to understanding how an essential yet novel protein functions in its fundamental role in cell division.Broader Impacts: Fundamental to understanding our natural world is not just to learn facts about it, but to understand where these facts come from. The best way for students to understand the scientific method is to spend time in a research setting as an active participant. Fairfield University undergraduate students will perform the experiments described in this proposal, gather empirical data from these experiments, and interpret these data to determine whether they support or refute our hypotheses. For many students, this will provide their first exposure to original research. Training students to engage research in this manner will make them better scientists. More importantly, these activities will help students develop into better thinkers and thus citizens more capable of making thoughtful decisions about how to run our society.