Coordination of replication and migration in an epithelial sheet

细胞迁移是一个高度整合的多步骤过程，是正常发育、受损组织修复以及癌症和动脉粥样硬化等疾病进展的基础。 细胞利用关键的信号蛋白，特别是蛋白激酶，来调节细胞分裂和细胞形状的变化，以实现适当的迁移。 果蝇Tribbles蛋白的功能是限制细胞分裂并促进细胞迁移过程中的蛋白质周转，并且与TRB蛋白家族相关，该蛋白家族包括人类SKIP-1，当突变时与称为急性髓细胞性白血病（AML）的白血病的侵袭性形式相关。 一个重要但尚未解决的问题是，这些蛋白质是作为激酶将磷酸分子连接到靶蛋白上，还是作为假激酶间接调节信号传导。 为了解决这个问题，PI的实验室将使用强大的遗传模型系统来表达Tribbles的正常和突变版本，并检查对细胞结构和蛋白质周转的影响。这些实验的结果将揭示Tribbles在正常发育过程中的分子功能，所提出的工作将培养本科生和研究生采用尖端方法来了解发育的遗传基础，并对人类疾病产生影响。

Cell migration is a highly integrated, multistep process that underlies normal development, repair of injured tissue, and the progression of diseases such as cancers and atherosclerosis. Cells utilize key signaling proteins, notably protein kinases, to regulate changes in cell division and cell shape for proper migration. The Drosophila Tribbles protein functions to restrict cell division and promote protein turnover during the cell migration process and is related to the TRB family of proteins that includes human SKIP-1, which when mutated is associated with an aggressive form of leukemia called acute myelogenous leukemia (AML). An important, but unresolved question is whether these proteins act as kinases to attach phosphate molecules to target proteins or rather as a pseudokinases to regulate signaling indirectly. To address this, the PI's laboratory will use a powerful genetic model system to express normal and mutated versions of Tribbles and examine effects on cell structure and protein turnover. The outcome of these experiments will shed light on the molecular function of Tribbles during normal development and the work proposed will train undergraduates and graduate students in cutting edge approaches to understand the genetic basis of development with implications for human disease.