Molecular Dynamic of Neurons during C. elegans Lifespan

该网络的目标是通过研究训练一组由10名年轻科学家组成的小组，为他们提供解决问题所必需的实用技能和知识。神经元的功能是由其形态受体和粘附蛋白（用于连接组的模式）、突触蛋白复合物（用于细胞间通信）和离子通道（用于神经元的兴奋性和信号传播）的表达决定的。任何神经元的蛋白质组成本身都依赖于受转录因子和转录后调控（剪接、翻译、蛋白质稳定性）控制的基因表达。最后，神经元是高度区隔的细胞，需要将蛋白质运送到正确的位置。因此，这些神经元特征的改变可以在多个层面上观察到：分子、细胞和行为。我们将重点关注神经元的三个特征：i)通过RNA测序和蛋白质组学测量的基因表达水平，ii)功能性多蛋白复合物的组装（通过高分辨率显微镜和邻近依赖的蛋白质标记），以及iii)通过光遗传学，钙成像和行为分析相结合的表型输出。这一研究项目将有助于定义区分给定神经元的生理和病理状态的关键特征。这些生物标志物对于促进药物筛选或开发人类神经系统疾病的新治疗策略将是宝贵的。跨学科研究和培训计划将涵盖广泛的方法和主题，从细胞间分子相互作用到细胞间通信，基因表达谱，有害突变的影响，行为研究和翻译调节。加上广泛的网络范围内的可转移技能培训，这将为研究员在神经生物学的医学重要领域以及包括政府和工业在内的广泛载体的职业生涯做好准备。

The objective of this network is to train, through research, a group of 10 young scientists, giving them the practical skills and knowledge necessary to tackleThe function of a neuron is determined by its expression of morphogen receptors and adhesion proteins (to pattern its connectome), of synaptic protein complexes (for intercellular communication), and of ion channels (for neuronal excitability and signal propagation). The protein composition of any neuron is itself dependent on gene expression controlled by transcription factors and by post-transcriptional regulations (splicing, translation, protein stability). Finally, neurons are highly compartmentalized cells and require trafficking of proteins to their correct locations. Alterations of these neuronal features can therefore be observed at multiple levels: molecular, cellular, and behavioral. We will focus on three neuronal features: i) gene expression levels as measured by RNA sequencing and proteomics, ii) assembly of functional multiprotein complexes (by high resolution microscopy and proximity dependent protein labelling), and iii) phenotypic output via a combination of optogenetics, calcium imaging, and behavioral assays.This research program will help define the critical features that differentiate between physiological and pathological states of a given neuron. Such biomarkers would be precious to facilitate drug screens or develop novel therapeutic strategies for human neurological diseases.The interdisciplinary research and training programme will cover a broad spectrum of approaches and topics, fromintracellular molecular interactions to cell-cell communication, gene expression profiling, the impact of deleterious mutations, behavioral studies, and translation regulation. Coupled with extensive network-wide transferable skills training, this will prepare the fellows for careers in the medically important field of neurobiology as well as a broad range of carriers including government and industry.