Metabolic regulation of inflammation; how energy controls immunity (BERAZA_F17DTP2)

炎症的代谢调节；

• 批准号: 1937607
• 金额: --
• 依托单位: University of East Anglia
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2017
• 资助国家: 英国
• 起止时间: 2017 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-1937607
• 关键词: Metabolic; regulation; inflammation; how; energy

Inflammation is the hallmark of chronic liver disease and mediates the transition between health and disease. The regulation of immune cell activation, including macrophages, is far more complex than initially described as there are increasing evidences of the role of metabolism in regulating immune cell function. In this line, recent work has shown that specific stimuli promote the metabolic reprogramming of macrophages, leading to changes on the proliferative and pro-inflammatory phenotype of these cells. The aim of this work is to investigate the mechanisms underlying metabolic reprogramming of immune cells and how the regulation of specific metabolic pathways, including autophagy, regulate the immune response. To define this is essential to develop anti-inflammatory strategies based on the regulation of metabolism to preserve health. Our work is of special relevance as we will investigate these in the context of the gut/liver axis and how metabolic regulation in either organ may impact on the function of this axis, providing a mechanistic view of this crosstalk.This collaborative and multidisciplinary study will allow the PhD candidate to develop both in vitro and in vivo work and to learn a variety of transferrable skills including basic molecular biology methodologies such as qPCR and Western blot analysis, histomorphological and immunohistochemical analysis and assessment of the immune response as well as cutting edge technologies as in vivo imaging and Seahorse analysis. This will enrich the student's professional curricula to enable a successful progression of her/his carer in the following stages.

炎症是慢性肝病的标志，并介导健康和疾病之间的过渡。免疫细胞（包括巨噬细胞）活化的调节比最初描述的要复杂得多，因为有越来越多的证据表明代谢在调节免疫细胞功能中的作用。在这条线上，最近的工作表明，特定的刺激促进巨噬细胞的代谢重编程，导致这些细胞的增殖和促炎表型的变化。这项工作的目的是研究免疫细胞代谢重编程的潜在机制，以及特定代谢途径（包括自噬）的调节如何调节免疫反应。定义这一点对于制定基于代谢调节的抗炎策略以保持健康至关重要。我们的工作具有特殊的相关性，因为我们将在肠道/肝脏轴的背景下研究这些，以及两个器官中的代谢调节如何影响该轴的功能，这种合作和多学科的研究将允许博士候选人开发体外和体内工作，并学习各种可转移的技能，包括基本的分子生物学方法，如qPCR和Western印迹分析、组织形态学和免疫组织化学分析和免疫反应评估以及体内成像和Seahorse分析等尖端技术。这将丰富学生的专业课程，使她/他的照顾者在以下阶段取得成功。

项目成果

Intestinal Microbiome-Macrophage Crosstalk Contributes to Cholestatic Liver Disease by Promoting Intestinal Permeability in Mice.

• DOI: 10.1002/hep.31228
• 发表时间: 2020-12
• 期刊: Hepatology (Baltimore, Md.)
• 作者: Isaacs-Ten A;Echeandia M;Moreno-Gonzalez M;Brion A;Goldson A;Philo M;Patterson AM;Parker A;Galduroz M;Baker D;Rushbrook SM;Hildebrand F;Beraza N
• 通讯作者: Beraza N

Fine-Tuning of Sirtuin 1 Expression Is Essential to Protect the Liver From Cholestatic Liver Disease.

SIRTUIN 1表达的微调对于保护肝脏免受胆​​固醇肝病至关重要。

• DOI: 10.1002/hep.30275
• 发表时间: 2019-03
• 期刊: Hepatology (Baltimore, Md.)
• 作者: Blokker BA;Maijo M;Echeandia M;Galduroz M;Patterson AM;Ten A;Philo M;Schungel R;Gutierrez-de Juan V;Halilbasic E;Fuchs C;Le Gall G;Milkiewicz M;Milkiewicz P;Banales JM;Rushbrook SM;Mato JM;Trauner M;Müller M;Martínez-Chantar ML;Varela-Rey M;Beraza N
• 通讯作者: Beraza N