RII Track-2 FEC-Genome to fitness: An Analysis of the Stress Response in Peromyscus

RII Track-2 FEC 基因组对健康的影响：白鼠应激反应分析

• 批准号: 1736150
• 负责人: Hippokratis Kiaris
• 金额: $ 389.85万
• 依托单位: University of South Carolina at Columbia
• 依托单位国家: 美国
• 项目类别: Cooperative Agreement
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1736150&HistoricalAwards=false
• 关键词: RII; Track; FEC; Genome; fitness

Non-technical description This Research Infrastructure Improvement Track-2 Focused EPSCoR Collaborations (RII Track-2 FEC) award explores how genetic differences determine the response of individual animals to various stress-inducing stimuli. At the level of a cell or an individual organism, stress-inducing stimuli can involve a number of factors such as oxygen deficiency, poor diet, or exposure to toxic chemicals. The stress responses vary among cells and tissue types and how these responses impact the animal?s functions and survival is not well understood. This project applies a combination of genomic analyses coupled with stress tests at cellular and organismal levels to understand the fitness of mammals using North American deer mouse as a model. The project is a collaborative effort that will be led by the University of South Carolina with faculty and students from Claflin University, an Historically Black College and University (HBCU) in South Carolina, and Auburn University in Alabama participating in the research, education, and outreach activities. A new Rodent Performance Testing Laboratory will be established at Auburn University and two early career faculty will be hired to augment and strengthen the resources for collaborations. Senior faculty members will provide strong mentorship for junior researchers for career advancement and will work together in training a diverse group of graduate and undergraduate students and postdocs. Technical descriptionThis collaborative project involving University of South Carolina, Claflin University, and Auburn University aims to dissect the genomic basis of stress response in mammals. The overarching goals of this study is to identify the genes and epigenes responsible for variation in endoplasmic reticulum (ER) stress and the resulting unfolded protein response (UPR) and to characterize the physiological and fitness ramification of these differences in out-bred North American deer mouse (Peromyscus maniculatus). Specifically, the planned research will: (1) identify and validate Quantitative Trait Loci correlated with UPR response in P. maniculatus; (2) establish cultures of primary fibroblasts from P. maniculatus and to perform analysis of the UPR in culture; (3) monitor the response of P. maniculatus in different environmentally-relevant diets; (4) associate genomic signatures and variation in the UPR profile of fibroblasts to variation in animal survival and reproductive performance under semi-natural conditions. The tools, methodologies, and reagents developed and optimized during this work will be made readily available to other researchers. The project will augment available resources by establishing a new Rodent Performance Testing Laboratory at Auburn University and by hiring two early career faculty with expertise in stress biology, evolution and genomics. Strong emphasis on mentoring of early career faculty and postdocs, development of new graduate courses, and recruitment of graduate and undergraduate students with particular emphasis on recruiting students from ethnic and other underrepresented minority groups in STEM are included in this project.

非技术描述这个研究基础设施改善Track-2专注于EPSCoR协作(RII Track-2 FEC)奖探索了遗传差异如何决定单个动物对各种应激诱导刺激的反应。在细胞或单个有机体的水平上，压力诱导刺激可能涉及许多因素，如缺氧、不良饮食或暴露在有毒化学物质中。应激反应因细胞和组织类型的不同而不同，这些反应如何影响动物？S的功能和生存尚不清楚。该项目将基因组分析与细胞和生物水平的压力测试相结合，以北美鹿鼠为模型来了解哺乳动物的健康状况。该项目由南卡罗来纳大学牵头，南卡罗来纳州克拉夫林大学、南卡罗来纳州历史上的黑人学院和大学(HBCU)以及阿拉巴马州奥本大学的教职员工和学生将参与研究、教育和外联活动。将在奥本大学建立一个新的啮齿动物性能测试实验室，并将聘请两名职业早期教师，以增加和加强合作资源。资深教员将为初级研究人员的职业发展提供强有力的指导，并将共同努力培养不同的研究生、本科生和博士后群体。这个由南卡罗来纳大学、克拉夫林大学和奥本大学参与的合作项目旨在剖析哺乳动物应激反应的基因组基础。本研究的主要目标是确定导致内质网(ER)应激和由此产生的未折叠蛋白反应(UPR)的差异的基因和表观基因，并表征这些差异在远交种北美鹿小鼠(Permyscus Manulatus)中的生理和适应性分支。具体地说，计划中的研究将：(1)确定和验证与马尾松UPR反应相关的数量性状基因座；(2)建立马尾松原代成纤维细胞的培养，并对培养物中的UPR进行分析；(3)监测马尾松在不同环境相关日粮中的反应；(4)将成纤维细胞的基因组特征和UPR图谱中的变异与半自然条件下动物存活和繁殖性能的变化联系起来。在这项工作中开发和优化的工具、方法和试剂将随时可供其他研究人员使用。该项目将通过在奥本大学建立一个新的啮齿动物性能测试实验室，并通过聘请两名具有压力生物学、进化和基因组学专业知识的早期教师来增加可用资源。该项目非常重视对早期就业教师和博士后的指导，开发新的研究生课程，以及招收研究生和本科生，特别重视招收STEM中少数民族和其他代表性不足的少数群体的学生。

项目成果

CCL8 Promotes Postpartum Breast Cancer by Recruiting M2 Macrophages

• DOI: 10.1016/j.isci.2020.101217
• 发表时间: 2020-06-26
• 期刊: ISCIENCE
• 影响因子: 5.8
• 作者: Farmaki, Elena;Kaza, Vimala;Kiaris, Hippokratis
• 通讯作者: Kiaris, Hippokratis

Coordination of the unfolded protein response during hepatic steatosis identifies CHOP as a specific regulator of hepatocyte ballooning

• DOI: 10.1007/s12192-020-01132-x
• 发表时间: 2020-06
• 期刊: Cell Stress and Chaperones
• 影响因子: 3.8
• 作者: Youwen Zhang;I. Chatzistamou;H. Kiaris

Life History Trade-offs within the Context of Mitochondrial Hormesis

• DOI: 10.1093/icb/icy073
• 发表时间: 2018-09-01
• 期刊: INTEGRATIVE AND COMPARATIVE BIOLOGY
• 影响因子: 2.6
• 作者: Hood, W. R.;Zhang, Y.;Kavazis, A. N.
• 通讯作者: Kavazis, A. N.

Maternal Dietary Protein Intake Influences Milk and Offspring Gut Microbial Diversity in a Rat (Rattus norvegicus) Model

• DOI: 10.3390/nu11092257
• 发表时间: 2019-09
• 期刊: Nutrients
• 影响因子: 5.9
• 作者: M. Warren;H. Hallowell;Keah V. Higgins;M. Liles;W. Hood

Beyond the Powerhouse: Integrating Mitonuclear Evolution, Physiology, and Theory in Comparative Biology

超越动力源：在比较生物学中整合线粒体核进化、生理学和理论

• DOI: 10.1093/icb/icz132
• 发表时间: 2019
• 期刊: Integrative and Comparative Biology
• 影响因子: 2.6
• 作者: Havird, Justin C.;Weaver, Ryan J.;Milani, Liliana;Ghiselli, Fabrizio;Greenway, Ryan;Ramsey, Adam J.;Jimenez, Ana G.;Dowling, Damian K.;Hood, Wendy R.;Montooth, Kristi L.
• 通讯作者: Montooth, Kristi L.