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 可以在萌芽酵母之间经历可逆的形态发生转变， 假菌丝和菌丝生长形态。它独特的能力可以从酵母菌转变为菌丝 响应各种寄主和环境信号的生长对其 致病性。许多菌丝特有的基因编码致病因子。连字符 发育受多条信号转导途径的调控。其中， CAMP依赖的蛋白激酶A(PKA)途径是形态发生的主要调节因子 和致命性。尽管cAMP-PKA很重要，但它的分子机制 激活菌丝转录程序的途径仍不清楚。我们找到了营地- 依赖PKA下调菌丝形态发生的主要抑制因子Nrg1， 与菌丝转录程序的启动有关。持续菌丝 转录需要Hda1被招募到菌丝特异基因的启动子中， 它会导致启动子染色质的变化。我们建议确定 CAMP-PKA依赖的Nrg1下调的机制和调节因子 Aim 1中的菌丝诱导。Aim 2定义了宿主因子(S)和白色念珠菌的途径 HDA1启动子招募及其在侵袭性念珠菌病中的重要性。AIM 3研究 Cph2的功能和调控。一种结合分子遗传学、细胞遗传学的方法 我们的学习将选修生物学和生物化学。这项工作将为我们提供一个 更好地理解白色念珠菌如何整合各种信号来控制生长和 发展，以及它如何在各种宿主环境中生存和发展。

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.