Regulation by Basic Helix-loop-helix Proteins in Yeast

Lopes实验室的长期目标是了解碱性螺旋-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蛋白如何在基因组规模上调节基因表达的理想模型系统。 S.酿酒酵母仅具有9种bHLH蛋白，其已经关于通常响应于单一环境线索的单一生物途径的调节进行了充分研究。 Lopes实验室最近的研究，在不同的生长条件下定量表达bHLH候选基因，通过几种机制提供了令人信服的证据，一个复杂的交叉调节网络。 这些结果强调了这样一个事实，即它们识别了酵母基因组数据库没有建议的调控事件。 该项目验证了bHLH蛋白通过多种机制调节靶基因的假设。 Lopes博士将确定bHLH蛋白对靶基因表达的自动和交叉调节作用。 他还将确定不同生长条件对bHLH定位和二聚化的影响。 本研究计画探讨两个重要的真核生物调控范例，基因表现的组合控制与协调。 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，该项目将用于培训研究生和本科生的主要研究。 bHLH蛋白质的普遍存在性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结果方面有着良好的记录。 洛佩斯博士还将创建一个创新的研究生水平的课程，完全集中在写作和审查科学手稿和赠款建议。

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.