Analysis of the C.albicansTranscriptome

描述（由申请人提供）：本项目将通过使用超高通量RNA测序，结合合理选择的不同实验条件，精确定义人类真菌病原体白色念珠菌基因组内所有转录本的身份和位置。C.白色念珠菌是一种越来越重要的人类病原体，由于患者群体不断扩大以及对现有抗真菌药物的耐药性不断增加，开发新的治疗方法至关重要。使用我们的方法很可能会鉴定出数百种新的转录本，其中许多可能是C。白色念珠菌或密切相关的物种;这些新的病原体特异性基因可能被证明是良好的治疗靶点。此外，我们将通过RT-PCR验证所有新的转录本，并确定哪些新的转录本可能编码蛋白质。最后，我们将进行初步的功能表征的新的成绩单，通过使用微阵列，以确定其相对丰度在各种使用的实验条件下，并通过识别与已知功能的基因，他们共同调节。这一提议是重要的，因为它直接推进了我们对这种医学上重要的人类真菌病原体的生物学的理解，并且因为来自其他生物体的类似研究强烈表明，拟议的实验将大大改进C.白色念珠菌基因组。因此，我们可以深入了解C。白念珠菌生物学的研究，也更广泛地有益于真菌基因组学领域，其长期目标是对人类患者治疗真菌感染的方式产生重大影响。利用C.白色念珠菌基因组，高通量测序技术的存在，以及公共念珠菌基因组学数据库，为成功完成该项目和将数据传播到真菌发病机制研究界以显著影响未来的念珠菌奠定了基础。白色念珠菌的研究，并最终治疗念珠菌病。 公共卫生相关性：白色念珠菌是一种越来越重要的人类病原体，新的治疗方法的开发是至关重要的，特别是考虑到最近在临床分离的念珠菌耐药性的上升。白色念珠菌。这项工作旨在确定新的基因在C。白念珠菌;很可能会鉴定出数百个新基因，其中许多可能被证明是良好的治疗靶点。因此，这项工作有可能对人类健康产生巨大的积极影响。

DESCRIPTION (provided by applicant): This project will define precisely the identity and positions of all transcripts within the genome of the human fungal pathogen Candida albicans, by using ultra high throughput RNA sequencing, in conjunction with a rationally chosen diverse set of experimental conditions. C. albicans is an increasingly important human pathogen, and, due to an expanding patient population and to increasing resistance to existing antifungal drugs, it is vital that new treatments are developed. It is likely that hundreds of new transcripts will be identified using our approach, and many of these may be specific to C. albicans or closely related species; these novel pathogen-specific genes may prove to be good therapeutic targets. In addition, we will validate all new transcripts by RT-PCR, and identify which of the new transcripts are likely to encode proteins. Finally, we will perform preliminary functional characterization of the novel transcripts, by using microarrays to determine their relative abundance under the various used experimental conditions, and by identifying with which genes of known function they are co-regulated. This proposal is significant both because it directly advances our understanding of the biology of this medically important human fungal pathogen, and because similar studies from other organisms strongly suggest that the proposed experiments will substantially refine the primary annotation of the C. albicans genome. We thus gain insight into C. albicans biology and also benefit the field of fungal genomics more widely, with the long-term goal of having a significant impact into the way in which fungal infections are treated in human patients. With a chromosome-level assembly of the C. albicans genome, the existence of high throughput sequencing technologies, and a public Candida genomics database, the groundwork is in place for both successful completion of this project and dissemination of the data to the fungal pathogenesis research community to significantly impact future C. albicans research, and, ultimately the treatment of Candida disease. PUBLIC HEALTH RELEVANCE: Candida albicans is an increasingly important human pathogen, and the development of new treatments is vital, especially given the recent rise in drug resistance among clinical isolates of C. albicans. This work seeks to identify novel genes within C. albicans; it is likely that hundreds of new genes will be identified, and of those, many may prove to be good therapeutic targets. Thus, this work has the potential for a large positive future impact on human health.