Excellence in Research: Crosstalk between the STK4/Hippo and NF-Kappa B pathway in mammalian cells

该项目的目标是了解细胞内的分子信号是如何在不断变化的环境条件下控制细胞大小和生长、细胞迁移和细胞存活的。使用在培养中培养的哺乳动物细胞，来自一所本科院校的本科生和研究生将使用一系列生化、分子生物学、遗传学和基因组学方法来确定来自不同信号通路的成分如何沟通以协调细胞生长。该项目将为本科生和研究生提供生物科学方面的培训和教育机会，使他们能够在学术界或生命科学行业进一步追求职业目标。此外，将该项目的研究成果纳入课堂课程将进一步提高他们在生命科学方面的教育和研究质量，通过扩大对国家STEM研究工作的参与，帮助减少STEM就业的差距。该项目将研究STK4/Hippo途径的关键核效应蛋白YAP/TEAD蛋白与转录因子NF-Kappa B(NF&A；B；B)的组成部分RELA之间相互作用的机制。本项目的目的是(A)确定调节YAP/TEAD和RELA相互作用的信号机制，(B)确定YAP/TEAD和RELA蛋白在细胞内物理相互作用的机制，以及(C)证明YAP/TEAD是否调节RELA-DNA相互作用以及RELA依赖的基因转录和细胞功能。该项目将使用的技术包括高通量RNA或DNA测序、CRISPR/Cas9辅助的基因组编辑、染色质免疫沉淀和其他分子分析以及生物信息学数据分析。这项研究的结果包括对哺乳动物细胞中STK4/河马和核因子B信号之间的串扰机制进行了全面的剖析。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

The goal of this project is to understand how molecular signals inside the cell are used to control cell size and growth, cell migration, and cell survival under changing environmental conditions. Using mammalian cells grown in culture, undergraduate and graduate students from an undergraduate institution that serves students from disproportionately underrepresented African-American communities will use a range of biochemical, molecular biology, genetics, and genomics approaches to determine how components from different signaling pathways communicate to coordinate cell growth. This project will provide undergraduate and graduate students with training and educational opportunities in biological sciences, allowing them to further pursue career goals in academia or in life sciences industries. Additionally, incorporation of research findings from this project into the classroom curriculum will further enhance their quality of education and research in life sciences, helping to reduce disparities in STEM employment by broadening participation in the Nation's STEM research workforce.This project will investigate the mechanism of the interaction between the YAP/TEAD protein, a key nuclear effector of the STK4/Hippo pathway, and RELA, a component of the NF-Kappa B (NFκB) transcription factors. The aims of this project are (a) to define the signaling mechanism that regulates YAP/TEAD and RELA interactions, (b) to determine the mechanism by which YAP/TEAD and RELA proteins physically interact in the cell, and (c) to demonstrate whether YAP/TEAD regulates the RELA-DNA interaction and the RELA-dependent gene transcription and cellular function. The techniques to be utilized in this project include high-throughput RNA or DNA sequencing, CRISPR/Cas9-aided genome editing, chromatin-immunoprecipitation and other molecular assays, and bioinformatics data analysis. The outcomes of this research include a comprehensive dissection of the mechanism of crosstalk between the STK4/Hippo and NFκB signaling in mammalian cells.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.