Discovery of gene function and dissection of network re-wiring in non-model fungi

非模式真菌基因功能的发现和网络重连的解析

• 批准号: 10710185
• 负责人: Teresa R. OMeara
• 金额: $ 38.22万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-28 至 2027-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10710185
• 关键词: Affect; Biological; Biology; Candida albicans; Candida auris; Case Study; Cells; Communities; Complication; Computer Models; Computing Methodologies; Data; Dissection; Evolution; Genes; Genetic Screening; Goals; Knowledge; Methods; Modeling; Molecular; Molecular Genetics; Organism; Proteins; Research; Role; Signal Transduction; Stimulus; Testing; Work; fungus; gene discovery; gene function; insight; interest; model building; pathogenic fungus; predictive modeling; programs; transcription factor; transcriptomics

PROJECT ABSTRACT The long-term goal of my research program is to be able to make mechanistic models for understudied fungi, thus allowing us to understand new aspects of fungal biology. To build these models, and predict how specific perturbations will affect the cell, it critical to have gene function annotations. However, the majority of the genes in non-model organisms are still unannotated and uncharacterized. Our interest therefore lies in building and testing computational models for predicting gene function in Candida auris, a newly emerging fungal pathogen. To carry out this work, we will perform high-throughput transcriptomic studies to generate a co- expression network, and then test the accuracy of this approach through functional genetic screening and detailed molecular genetics. As an additional complication to understanding gene function, regulatory network re-wiring is common throughout evolution, where the same key proteins respond to a suite of different inputs. Understanding how these signaling cascades can be re-wired will give insight into both gene function and the environmental stimuli that drive these changes. We will dissect, in molecular detail, the role of cis and trans factors in network re-wiring between C. albicans and C. auris, using a conserved transcription factor as a case study. These studies will provide fundamental data and cell biological knowledge to the community studying fungi, and more broadly to those studying non-model organisms.

项目摘要 我的研究计划的长期目标是能够为未被研究的人建立机械模型。 真菌，从而使我们能够了解真菌生物学的新方面。来建立这些模型，并预测 特定的扰动会影响细胞，这对基因功能注释至关重要。但大多数 非模式生物中的基因仍然未被注释和表征。因此，我们的兴趣在于 构建和测试用于预测新出现的真菌耳念珠菌中基因功能的计算模型 病原体为了开展这项工作，我们将进行高通量转录组学研究，以产生一个共同的， 表达网络，然后通过功能遗传筛选和 详细的分子遗传学作为理解基因功能的另一个复杂因素，调控网络 在整个进化过程中，重新连接是很常见的，相同的关键蛋白质会对一系列不同的输入做出反应。 了解这些信号级联是如何重新连接的，将有助于深入了解基因功能和基因表达。 环境刺激推动这些变化。我们将从分子的细节上剖析顺式和反式 C之间网络重新布线的因素。白色念珠菌和C.耳，使用保守的转录因子作为案例， study.这些研究将为社区研究提供基础数据和细胞生物学知识 真菌，更广泛地说，研究非模式生物。