唑类药物是麦角甾醇的合成抑制剂，是临床和农业上使用最广泛的抗真菌药物。在唑类药物胁迫下，真菌很多基因会出现适应性的转录响应，促进真菌在药物环境下生存。ADS-1是我们发现的一个新转录因子。ADS-1的缺失会使粗糙脉孢菌对唑类药物的敏感性增强，而过表达能使粗糙脉孢菌对唑类药物的耐受性增强。ADS-1的同源蛋白在丝状真菌中普遍存在，将其轮枝镰刀菌、黄曲霉中ADS-1的同源蛋白编码基因敲除之后，突变体对唑类药物的敏感性也增强，说明该转录因子的功能保守。ADS-1及其同源蛋白在抗真菌药物胁迫响应中的作用与机制尚未见报道。本项目将以粗糙脉孢菌为模式材料，鉴定转录因子ADS-1所调控的基因，明确这些基因在真菌对唑类抗真菌药物的适应性响应中作用，鉴定ADS-1所结合的DNA序列的共性特征，分析ADS-1与其它转录因子在唑类药物胁迫响应过程中的分工与协作关系，最终揭示ADS-1对唑类响应的机制。

The antifungal azoles, including imidazoles and triazoles, are the major drugs for fungal infections. Some azoles are also applied as pesticides. Azoles disrupt ergosterol biosynthesis by inhibiting the enzyme 14α-demethylase. Fungi are able to adapt to azole stress by altering transcriptional levels of many genes. Overexpression of some azole-responsive genes, such as azole target gene ERG11 or azole pumps encoding genes, has been demonstrated to be able to increase azole resistance in many fungi. Thus, the transcriptional response is an adaptive response to azole stress, which promote fungi to survive under azole stress. Our group found a novel transcription factor named as ADS-1 (antifungal drug sensitive-1). Its coding gene ads-1 increases transcriptional levels under ketoconazole stress. Deletion of ads-1 resulted in hypersusceptibility to antifungal azoles while its overexpression make N. crassa more resistant to azoles. ADS-1 homologs widely present in filamentous fungi. Deletion of ADS-1 homologue encoding genes fvads-1 in Fusarium verticillioides and afads-1 in Aspergillus flavus also make these two fungi hypersensitive to antifungal azoles. Thus, ADS-1 homologs are functional among different fungal species. In this study, we propose to investigate the mechanism by which ADS-1 promote fungal adaptation under azoles using N. crassa as a model. We will identify the genes regulated by ADS-1 by RNA-seq followed with result confirmation by qRT-PCR. We then test the azole susceptibility of gene knockout mutants of ADS-1-regulated genes to determine the roles of ADS-1-regulated genes in azole adaptation. We will also identify genome-wide DNA regions where ADS-1 binds with ChIP-seq. Based one the DNA sequence analysis, we will conclude the consensus motifs recognized and bound by ADS-1. In addition, we will analyze the relationship among ADS-1 and other transcription factors including CCG-8 and ADS-4. Finally, the role and mechanisms of ADS-1 in the network of azole response will be revealed.