CAREER: Inference of transcriptional regulation under environmental perturbations

职业：环境扰动下转录调控的推断

基本信息

批准号：
1846559
负责人：
Gerald Quon
金额：
$ 85.72万
依托单位：
University of California-Davis
依托单位国家：
美国
项目类别：
Continuing Grant
财政年份：
2019
资助国家：
美国
起止时间：
2019-06-01 至 2025-05-31
项目状态：
未结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1846559&HistoricalAwards=false
关键词：
CAREER Inference transcriptional regulation under

项目摘要

The genome defines blueprints necessary for the proper functioning of cells, and for complex organisms, such as vertebrates, it is nearly identical for most cells that make up the individual. Despite this, cells vary widely in shape and function. Understanding the mechanisms by which individual cells are set on the path to, and then maintain, their identity and function, and how they communicate with each other in order to coordinate development of the whole organism, is of keen interest to developmental biologists. The goals of this project are two-fold. First, it develops computational tools for 1) characterizing the impact of cell-cell communication on molecular function, 2) measuring biological variation in molecular function between cells collected from different tissues or individuals, and 3) predicting experimental strategies for manipulating cell identity and function. Second, it trains high school, undergraduate and graduate students in the use of these tools and data analysis techniques, and develops approaches to engage students in interdisciplinary team-based genomics research. The project will thus achieve the broader goal of training the next generation of data scientists to address important problems in biology using genomics technologies. Recent developments in DNA sequencing technologies enable the measurement of different dynamic aspects of gene regulation across a wide spectrum of organisms. For each segment of DNA in a genome, we can now measure a snapshot of its physical accessibility, measure its relative rate of transcription into RNA, identify the location of reversible modifications to the DNA or its anchoring proteins, and even identify other distal DNA segments that are in physical contact with it. The research goal of this project is to quantitatively characterize the mechanisms by which signals from both intrinsic and extrinsic factors are integrated to drive variation in gene and chromatin regulation, and ultimately define cell identity and its dynamics. It specifically develops tools based on deep neural networks to perform in silico perturbations to cells in order to identify the regulators of transcriptional cell state, identify regulatory pathways underlying cellular responses to stimuli, and characterize the effect of cell-cell communication on gene regulation. The educational goal of this project is to develop scalable strategies to train the next generation of genome data scientists at the high school, undergraduate and graduate levels of education to use these tools to address diverse problems in biology in an interdisciplinary team-based science approach. The results of this work can be found at http://qlab.faculty.ucdavis.edu.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

基因组定义了细胞正确功能所必需的蓝图，对于脊椎动物等复杂的生物，对于大多数组成个体的细胞而言，它几乎是相同的。尽管如此，细胞的形状和功能差异很大。了解开发生物学家的兴趣，了解各个细胞设置在通往其身份和功能的道路上，然后维持其身份和功能以协调整个生物体的发展以互相交流的机制。该项目的目标是两个方面。首先，它开发了用于1）表征细胞 - 细胞通信对分子功能的影响的计算工具，2）测量从不同组织或个体收集的细胞之间分子功能的生物学变化，以及3）预测操纵细胞身份和功能的实验策略。其次，它培训了高中，本科和研究生的使用这些工具和数据分析技术，并开发了吸引学生参与基于跨学科的基因组学研究的方法。因此，该项目将实现更广泛的目标，即培训下一代数据科学家使用基因组技术解决生物学的重要问题。 DNA测序技术的最新发展使得能够测量各种生物体的基因调节的不同动态方面。对于基因组中DNA的每个段，我们现在可以测量其物理可及性的快照，测量其相对的转录速率，确定可逆修改对DNA或其锚定蛋白的位置，甚至识别其他与之物理接触的远端DNA片段。该项目的研究目标是定量表征来自内在和外在因子的信号的机制，以驱动基因和染色质调节的变化，并最终定义细胞身份及其动力学。它专门开发基于深层神经网络的工具，以在对细胞的硅扰动中执行，以识别转录细胞状态的调节因子，确定对刺激的细胞反应的调节途径，并表征细胞细胞通信对基因调节的影响。该项目的教育目标是制定可扩展的策略，以培训高中，本科和研究生教育水平的下一代基因组数据科学家，以使用这些工具来解决基于跨学科的团队科学方法的生物学问题。这项工作的结果可以在http：//qlab.faculty.ucdavis.edu..edu..edu..edu..edu..ed..ed..ed..ed..ed..ed..ed..ed..edu..edu..edu..edu..edu..edu..edu..edu..edu..edu..edu..edu..edu..edu.edu.edu.edu..edu.edu..edu.edu.edu.ed.ucd.ucdavis.edu.edu.edu.edu.ucd.ucdavis.edu.edu。