The Structural Biology of Memory

我们感兴趣的是了解负责大脑中信息获取和存储的分子机制，即学习和记忆。过去50年的研究导致了这样一种想法，即神经细胞之间突触强度的活动依赖性变化（突触可塑性）可以代表信息存储的机制。神经递质谷氨酸和？-氨基丁酸（GABA）介导脊椎动物中枢神经系统中的大多数突触信号传导。它们的受体在突触可塑性的诱导、表达和/或调节中起重要作用。这些分子系统的功能障碍似乎是与“正常”衰老过程相关的认知能力下降的原因。从医学的角度来看，包括阿尔茨海默氏症、帕金森氏症、精神分裂症、双相情感障碍、严重临床抑郁症以及缺血性神经元损伤在内的各种疾病都与相同的受体分子有关。我们的研究目前主要集中在谷氨酸和GABA受体的结构表征上，我们的主要工具是X射线晶体学。我们的目标是了解它们的组装，功能和调节的分子机制，并设计调节其信号传导特性的方法。这项工作是使用培养中生长的细胞和最先进的技术进行的，包括用于生长蛋白质晶体和同步加速器产生的X射线的机器人。

We are interested in understanding the molecular mechanisms responsible for acquisition and storage of information in the brain, i.e. learning and memory. Research over the past five decades led to the idea that activity-dependent changes in the strength of synapses between nerve cells (synaptic plasticity) can represent a mechanism for information storage. The neurotransmitters glutamate and ?-amino-butyric acid (GABA) mediate most synaptic signalling in the vertebrate central nervous system. Their receptors play important roles in the induction, expression and/or modulation of synaptic plasticity. Dysfunction of these molecular systems appears to be responsible for the cognitive decline linked to the ‘normal‘ aging process. From a medical point of view, a wide spectrum of disorders including Alzheimer‘s, Parkinson‘s, schizophrenia, bipolar disorder, major clinical depression as well as ischemic neuronal injury are linked to the same receptor molecules.Our research is currently focused on the structural characterization of glutamate and GABA receptors, our main tool being X-ray crystallography. We aim to understand the molecular mechanisms governing their assembly, function and regulation, and to devise ways of modulating their signalling properties. This work is performed using cells grown in culture and state-of-the-art technology including robots for growing protein crystals and synchrotron-generated X-rays.