Carina Villegas Diversity Supplement

项目摘要 我们的研究重点是控制细胞生长和分裂周期的机制。的 对调节分裂决定的蛋白质和途径的鉴定导致了抑制剂的产生， 癌然而，这些抑制剂的缺点清楚地表明，仍有许多分子 细胞周期控制方面，我们不了解，需要进一步的研究创新 改善治疗。细胞周期由两波基因表达组成，以复制DNA， 进行有丝分裂。我们将研究控制这种细胞的蛋白质的结构，功能和调节- 周期依赖性基因表达这些蛋白质包括转录因子或TF（例如E2 F、B- Myb，FoxM 1），其活性刺激转录，负调节TF的蛋白质（例如Rb， CycF和MuvB复合物），以及磷酸化和磷酸化细胞的激酶（例如Cdk、Aurora A和Plk 1）。 调节TF活性。我们将使用一种综合方法，将结构生物学与细胞- 基于分析，以确定这些蛋白质如何相互作用和染色质控制 转录。这些研究将提供关于细胞周期是如何被激活的新的机制见解。 控制和转录因子如何直接调节基因表达，通过影响 染色质结构

PROJECT SUMMARY Our research is focused on the mechanisms that control the cell cycle of growth and division. The identification of proteins and pathways that regulate the decision to divide has led to inhibitors to treat cancer. However, the shortcomings of these inhibitors make it clear that there are still many molecular aspects of cell-cycle control that we do not understand, and further research is needed to innovate improved therapies. The cell cycle consists of two waves of gene expression to replicate DNA and undergo mitosis. We will study the structure, function, and regulation of proteins that control this cell- cycle dependent gene expression. These proteins include the transcription factors or TFs (e.g. E2F, B- Myb, FoxM1) whose activity stimulates transcription, proteins that negatively regulate the TFs (e.g. Rb, CycF, and the MuvB complex), and the kinases (e.g. Cdk, Aurora A, and Plk1) that phosphorylate and modulate TF activity. We will use an integrated approach that combines structural biology with cell- based assays to determine how these proteins interact with each other and chromatin to control transcription. These studies will provide new mechanistic insights regarding how the cell cycle is controlled and how transcription factors directly modulate gene expression through influencing chromatin structure.