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制作机械模型 真菌，从而使我们能够理解真菌生物学的新方面。建立这些模型，并预测如何 特定的扰动会影响细胞，具有基因功能注释至关重要。但是，大多数 非模型生物中的基因仍然未被注释且未表征。因此，我们的兴趣在于 用于预测念珠菌中基因功能的构建和测试计算模型，这是一种新兴的真菌 病原。为了进行这项工作，我们将进行高通量转录组学研究，以产生共同 表达网络，然后通过功能性遗传筛选测试这种方法的准确性 详细的分子遗传学。作为理解基因功能的另一个复杂性，调节网络 在整个演化过程中，重新开启是常见的，其中相同的关键蛋白对不同输入的套件做出反应。 了解如何重新连接这些信号级联对于基因功能和 驱动这些变化的环境刺激。我们将从分子细节上剖析顺式和反式的作用 使用保守的转录因子作为情况 学习。这些研究将为社区研究提供基本数据和细胞生物学知识 真菌，更广泛地针对那些研究非模型生物的人。