Regulation by Basic Helix-loop-helix Proteins in Yeast

Lopes实验室的长期目标是了解基本螺旋-环-螺旋（bHLH）转录因子调节基因表达的机制。bHLH家族在真核生物中普遍存在，并调节多种过程，包括发育、分化和细胞增殖。酿酒酵母是研究bHLH蛋白如何在基因组尺度上调控基因表达的理想模型系统。酿酒酵母只有9个bHLH蛋白，这些蛋白在响应单一环境线索的单一生物途径的调节方面已经得到了很好的研究。Lopes实验室最近的研究量化了bHLH候选基因在不同生长条件下的表达，为通过多种机制进行交叉调控的复杂网络提供了令人信服的证据。这些结果强调了这样一个事实，即他们确定了酵母基因组数据库未提示的调控事件。本项目验证了bHLH蛋白通过多种机制调控靶基因的假说。Lopes博士将确定bHLH蛋白在靶基因表达中的自动调节和交叉调节的作用。他还将确定不同生长条件对bHLH定位和二聚化的影响。本研究主要研究真核生物的两种重要调控模式：组合调控和基因表达协调。这个项目直接解决了生物学中的一个基本问题：基因是如何开启和关闭的？Lopes博士致力于指导，该项目将用于培养研究生和本科生的初级研究。bHLH蛋白的无所不在的性质确保了这些发现将吸引广泛的研究社区，Lopes博士在同行评审期刊上传播研究成果方面有着良好的记录。Lopes博士还将创建一门创新的研究生课程，完全专注于撰写和审查科学手稿和拨款提案。

The long-term goal of the Lopes lab is to understand the mechanisms whereby basic helix-loop-helix (bHLH) transcription factors regulate gene expression. The bHLH family is ubiquitous among eukaryotes and regulates a diverse set of processes including development, differentiation, and cell proliferation. Saccharomyces cerevisiae is an ideal model system to examine how bHLH proteins regulate gene expression on a genomic scale. S. cerevisiae only has 9 bHLH proteins, which have been well studied with respect to regulation of single biological pathways typically in response to single environmental cues. Recent studies in the Lopes lab, quantifying expression of bHLH candidate genes under a diverse set of growth conditions, provide compelling evidence for an elaborate network of cross-regulation via several mechanisms. These results are underscored by the fact that they identify regulatory events that are not suggested by yeast genomic databases. This project tests the hypothesis that bHLH proteins regulate target genes via multiple mechanisms. Dr. Lopes will determine the role of auto- and cross-regulation of bHLH proteins on target gene expression. He will also determine the effect of different growth conditions on bHLH localization and dimerization. This research project addresses two important eukaryotic regulatory paradigms, combinatorial control and coordination of gene expression. This project directly addresses a fundamental question in biology: how are genes turned-on and turned-off? Dr. Lopes is committed to mentoring and this project will be employed to train both graduate and undergraduate students in primary research. The ubiquitous nature of bHLH proteins ensures that the findings will appeal to a broad research community and Dr. Lopes has a strong record of disseminating research findings in peer-reviewed journals. Dr. Lopes will also create an innovative graduate level course focused entirely on writing and reviewing scientific manuscripts and grant proposals.