Regulation of Filamentous Growth in Yeast

白色念珠菌是人类最常见的真菌病原体之一。它 可以在芽殖酵母之间进行可逆的形态发生转变， 假菌丝和菌丝生长型。它独特的能力，从酵母菌转换为菌丝 响应各种宿主和环境信号的生长对于其 致病性许多菌丝特异性基因编码毒力因子。菌丝 发育受多种信号转导途径调控。其中以 cAMP依赖的蛋白激酶A（PKA）途径是形态发生的主要调节因子 和毒性。尽管cAMP-PKA的重要性， 途径激活菌丝转录程序仍然未知。我们发现环磷酸腺苷- 菌丝形态发生的主要阻遏物Nrg 1的PKA依赖性下调， 与菌丝转录程序的启动相关。持续菌丝 转录需要Hda 1被募集到菌丝特异性基因的启动子， 导致启动子染色质的改变。我们建议确定 cAMP-PKA依赖性Nrg 1下调的机制和调节剂 目的1菌丝诱导。目标2定义宿主因子和C。白念珠菌途径 Hda 1启动子募集及其在侵袭性念珠菌病中的重要性Aim 3研究 CPH 2的功能和调节。利用分子遗传学、细胞遗传学、 生物学和生物化学是我们学习的内容。这项工作将为我们提供一个 更好地理解C。白色念珠菌整合各种信号来控制生长， 开发，以及它如何在各种主机环境中生存和发展。

Candida albicans is one of the most frequently isolated fungal pathogens of humans. It can undergo reversible morphogenetic transitions between budding yeast, pseudohyphal, and hyphal growth forms. Its unique ability to switch from yeast to hyphal growth in response to various host and environmental signals is essential to its pathogenicity. Many hypha-specific genes encode virulence factors. Hyphal development is regulated by multiple signal transduction pathways. Among them, the cAMP-dependent protein kinase A (PKA) pathway is a major regulator of morphogenesis and virulence. Despite its importance, the molecular mechanism for how the cAMP-PKA pathway activates the hyphal transcriptional program is still not known. We find cAMP- PKA dependent down-regulation of the major repressor of hyphal morphogenesis, Nrg1, correlates with the initiation of the hyphal transcriptional program. Sustained hyphal transcription requires Hda1 being recruited to the promoters of hypha-specific genes, where it leads to changes in promoter chromatin. We propose to determine the mechanisms and regulators for cAMP-PKA dependent Nrg1 down-regulation upon hyphal induction in Aim 1. Aim 2 defines host factor(s) and C. albicans pathways for the promoter recruitment of Hda1 and its importance in invasive candidiasis. Aim 3 studies functions and regulation of Cph2. A combined approach using molecular genetics, cell biology and biochemistry will be taken in our studies. This work will provide us with a better understanding of how C. albicans integrates various signals to control growth and development, and how it survives and grows in various host environments.