CAREER: Regulation and Function of STAT Signaling in Cell Adhesion and Detachment

当胚胎发育时，细胞通常在一个地方出生，但在另一个地方需要。科学家们正在寻找控制细胞移动或停留的关键决定的分子机制。Starz-Gaiano博士和其他人发现了一个被称为信号转导和转录激活因子(STAT)途径的分子级联，在决定细胞是否可以运动的过程中发挥了关键作用。这一途径对于一些细胞保持干细胞身份，而不是发育成另一种细胞也是至关重要的。斯塔兹-盖亚诺博士的实验室将使用遗传学、分子和数学方法来了解STAT信号如何控制这些细胞事件。果蝇将被用于这些研究，因为它们有几个优势：快速发展，小而特征明确的基因组，许多遗传方法，以及透明的组织，使细胞在移动时能够可视化。斯塔兹-盖亚诺博士希望发现STAT信号在特定细胞中被关闭的机制，确定STAT用来改变细胞粘附性的关键分子，并将运动细胞的特性与干细胞维持所需的特性进行比较。解开细胞决策的分子奥秘对于理解正常发育、出生缺陷和疾病进展至关重要。由于80%以上的果蝇基因也在人类身上发现，该项目中确定的分子机制可能会得到广泛应用。这项研究将影响分子信号、细胞运动性、干细胞生物学和自然现象的数学模型等领域。这些项目也处于有利地位，可以通过跨学科伙伴关系加强教育，并将利用密歇根大学国家认可的项目，增加未被充分代表的学生参与科学。因此，拟议的活动将把广泛相关的跨学科研究与同时面向下一代公民和潜在科学家的杰出教育结合起来。

When embryos develop, cells are often born in one location but required at another. Scientists are searching for the molecular mechanisms that govern the critical decision of a cell to move or stay in place. Dr. Starz-Gaiano and others have uncovered a pivotal role for a molecular cascade, called the Signal Transducer and Activator of Transcription (STAT) pathway, in determining whether a cell will become motile. This pathway is also essential for some cells to remain as stem cells instead of developing into another kind of cell. Dr. Starz-Gaiano's laboratory will use genetic, molecular, and mathematical approaches to understand how STAT signaling controls these cellular events. Fruit flies will be used in these studies because they have several advantages: rapid development, a small and well-characterized genome, many genetic methods, and transparent tissues that enable visualization of cells as they move. Dr. Starz-Gaiano expects to discover the mechanism by which STAT signaling is turned off in select cells, to identify the critical molecules that STAT employs to change the adhesiveness of cells, and to compare the properties of motile cells to those required for stem cell maintenance. Unlocking the molecular mysteries of cellular decision-making is essential in understanding normal development, birth defects, and disease progression. Because over 80% of fruit fly genes are also found in humans, the molecular mechanisms identified in this project will likely be broadly applicable. This research will impact the fields of molecular signaling, cell motility, stem cell biology, and mathematical modeling of natural phenomena. The projects are also well-positioned to enhance education through interdisciplinary partnerships and will leverage UMBC's nationally-recognized programs that increase involvement of underrepresented students in science. Thus, the proposed activities will integrate widely relevant, interdisciplinary research with simultaneous, outstanding education for the next generation of citizens and potential scientists.