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发生的最具活力的事件。必须协调多个亚细胞过程，以确保细胞材料的正确分离和细胞质分裂的成功完成。例如，核膜在S阶段是完整的，确保了dna复制的正确完成，但当染色体在中期平板上排列时，核膜完全分解。为了使纺锤体微管接触浓缩的染色体并将它们拉到合适的极点，这种分解是必不可少的。关于核膜的形成和破裂如何与DNA复制和染色体分离相协调，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理，从而管理细胞分裂期间发生的多个并发事件。费尔南德斯博士发现了一种名为MEL-28(脊椎动物中的Elys)的新型AT-Hook结构域蛋白，该蛋白对核膜功能以及染色质形态和运动的适当调节都是必需的。该项目将对MEL-28进行功能研究，以更好地了解该蛋白质如何协调两个不同的过程。智力上的优点：同时亚细胞过程的协调是成功完成细胞分裂的关键，因此更好地了解这一过程是如何完成的，对于了解细胞如何分裂至关重要。费尔南德斯博士已经证明，MEL-28对于核膜的结构和功能的完整性以及染色质的适当形态、凝集状态和定位是必需的。然而，由于Mel-28是一个很大的蛋白质，几乎没有保守结构域，所以Mel-28蛋白是如何完成这些任务的在很大程度上仍然是未知的。因此，这项工作将有助于理解一种基本而又新颖的蛋白质如何在细胞分裂中发挥其基本作用。博德影响：理解我们的自然世界的基本原理不仅是了解它的事实，而且是理解这些事实的来源。对于学生来说，理解科学方法的最好方法是作为积极参与者花时间在研究环境中。费尔菲尔德大学的本科生将进行这项提案中描述的实验，从这些实验中收集经验数据，并对这些数据进行解读，以确定他们是支持还是驳斥我们的假设。对于许多学生来说，这将是他们第一次接触到原创研究。训练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考者，从而更有能力对如何管理我们的社会做出深思熟虑的决定。

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.