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

炎症是慢性肝病的标志，调节着健康和疾病之间的过渡。随着越来越多的证据表明新陈代谢在调节免疫细胞功能中的作用，对包括巨噬细胞在内的免疫细胞激活的调控比最初描述的要复杂得多。在这方面，最近的工作表明，特定的刺激促进巨噬细胞的代谢重新编程，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，以及包括自噬在内的特定代谢途径的调节如何调节免疫反应。确定这一点对于开发基于新陈代谢调节的抗炎策略以保护健康至关重要。我们的工作具有特别的相关性，因为我们将在肠道/肝脏轴的背景下研究这些，以及两个器官中的新陈代谢调节如何影响这一轴的功能，提供这一交叉的机制视图。这项合作和多学科的研究将使博士生能够发展体外和体内工作，并学习各种可转移的技能，包括基本的分子生物学方法，如定量聚合酶链式反应和免疫印迹分析，组织形态和免疫组织化学分析和免疫反应的评估，以及尖端技术，如体内成像和海马分析。这将丰富学生的专业课程，使她/他的照顾者在接下来的阶段取得成功的进步。

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.