A Systems Biological Approach to Elucidate Local Protein Synthesis Code in Plasticity and Memory

阐明可塑性和记忆中局部蛋白质合成代码的系统生物学方法

• 批准号: BB/I004483/1
• 负责人: Christopher Proud
• 金额: $ 32.99万
• 依托单位: University of Southampton
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2010
• 资助国家: 英国
• 起止时间: 2010 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FI004483%2F1
• 关键词: Systems; Biological; Approach; Elucidate; Local

Diseases which affect the nervous system such as Alzheimer's, Parkinson's, depression and schizophrenia account for the single largest cost to the healthcare system of the UK and are often associated with long-term disability, and distress for patients and their families. A common clinical feature of many of these and other disorders is a cognitive (often learning/memory) deficit. However learning and memory is a very complex biological process that is only partly understood. Of particular interest to us are the changes that occur after learning (i.e. during memory establishment) in the synapses - the critical structures that join two neurons together and mediate information flow and processing in all brains. In this study we aim to identify the biochemical changes (at the protein level) that are associated with forming memories. In particular, we aim to test the involvement of several candidate molecules that have been implicated but whose importance has not yet been proven. This work will also allow us to try and bridge the gap between what we see at the biochemical level in terms of molecules and their abundance with the actual behaviour of the brain (and subsequently of the animal). The observed biochemical changes will be used to refine and extend computational models of neuronal synapses. These computational models will provide a unique method to visualise these complex biochemical networks which involve more than 1000 proteins. Mathematical methods will then be applied that allow us to predict which molecules are more likely to be involved in the memory and a selection of the best candidates will be tested in the laboratory. These new insights will help us understand how memory is formed in the brain. Unravelling these core biological processes is vital to our understanding of animal behaviour in the first instance. In the longer term our research will have relevance to human cognition ultimately aiding the search for new drug therapies for cognitive illness.

影响神经系统的疾病，如阿尔茨海默氏症、帕金森氏症、抑郁症和精神分裂症，是英国医疗保健系统的最大单一成本，通常与长期残疾有关，并给患者及其家人带来痛苦。许多这些和其他疾病的共同临床特征是认知（通常是学习/记忆）缺陷。然而，学习和记忆是一个非常复杂的生物学过程，人们只对它有部分了解。我们特别感兴趣的是突触在学习后（即记忆建立期间）发生的变化，突触是将两个神经元连接在一起并介导所有大脑中的信息流和处理的关键结构。在这项研究中，我们的目标是确定与记忆形成相关的生化变化（在蛋白质水平上）。特别是，我们的目标是测试参与的几个候选分子，已牵连，但其重要性尚未得到证明。这项工作还将使我们能够尝试弥合我们在生物化学水平上看到的分子及其丰度与大脑（以及随后的动物）实际行为之间的差距。所观察到的生物化学变化将被用于改进和扩展神经元突触的计算模型。这些计算模型将提供一种独特的方法来可视化这些涉及1000多种蛋白质的复杂生化网络。然后将应用数学方法，使我们能够预测哪些分子更有可能参与记忆，并选择最佳候选人在实验室进行测试。这些新的见解将帮助我们了解记忆是如何在大脑中形成的。解开这些核心生物过程对于我们首先理解动物行为至关重要。从长远来看，我们的研究将与人类认知相关，最终有助于寻找治疗认知疾病的新药物。

项目成果

Quantitative Non-canonical Amino Acid Tagging (QuaNCAT) Proteomics Identifies Distinct Patterns of Protein Synthesis Rapidly Induced by Hypertrophic Agents in Cardiomyocytes, Revealing New Aspects of Metabolic Remodeling.

• DOI: 10.1074/mcp.m115.054312
• 发表时间: 2016-10
• 期刊: Molecular & cellular proteomics : MCP
• 作者: Liu R;Kenney JW;Manousopoulou A;Johnston HE;Kamei M;Woelk CH;Xie J;Schwarzer M;Garbis SD;Proud CG
• 通讯作者: Proud CG

Consolidation and translation regulation.

• DOI: 10.1101/lm.026849.112
• 发表时间: 2012-08-16
• 期刊: Learning & memory (Cold Spring Harbor, N.Y.)
• 作者: Gal-Ben-Ari S;Kenney JW;Ounalla-Saad H;Taha E;David O;Levitan D;Gildish I;Panja D;Pai B;Wibrand K;Simpson TI;Proud CG;Bramham CR;Armstrong JD;Rosenblum K
• 通讯作者: Rosenblum K