Characterisation of seizure-suppressor genes in Drosophila

哺乳动物的中枢神经系统由许多不同类型的神经细胞组成。这些细胞在它们接触的目标，它们释放的信号化学物质（神经递质）以及它们能够激发触发神经递质释放的电动作电位的方式方面有所不同。神经元功能的任何这些方面的缺失都有可能导致神经系统疾病，包括但不限于精神分裂症、抑郁症和癫痫。因此，为了设计出更好、更有效的神经系统疾病治疗方法，需要充分了解其根本原因。癫痫就是一个很好的例子。目前，只有大约70%的患者对药物治疗有反应，其余30%没有反应。显然需要额外的药物。然而，在设计新药之前，首先需要确定新的靶分子。只有在鉴定之后，药物才能被设计成与这些分子相互作用并对其产生影响。为此，我们使用果蝇，黑腹果蝇，因为它非常适合遗传分析，它的基因组已经测序，因为它提供了一个简单的，但可比较的，人类神经系统的模型。对于该项目具有重要意义的是，已经确定了许多突变，使苍蝇容易发生癫痫样发作。苍蝇的癫痫发作与人类的癫痫发作非常相似。利用果蝇的遗传易处理性，我们希望找到新的基因，这些基因在受到错误调节时可以改善癫痫发作，并通过这样做，为人类药物设计找到新的途径。

The mammalian central nervous system is composed of many different types of nerve cells. These cells differ in the target that they contact, the signalling chemicals (neurotransmitters) they release, and the way in which they are able to fire electrical action potentials that trigger release of their neurotransmitter(s). Abnormalities in any of these aspects of neuron function have the possibility to result in neurological disorders including, but not limited to, schizophrenia, depression and epilepsy. It is implicit, therefore, that in order to design better and more effective treatments for neurological disorders, the underlying causes need to be fully understood. Epilepsy is a case in point. Currently only about 70% of sufferers respond to drug treatment; the remaining 30% do not. Clearly additional drugs are required. However, before new drugs can be designed, novel target molecules need first to be identified. Only after identification can drugs be designed to interact with and effect such molecules. To this end, we are using the fruitfly, Drosophila melanogaster, because it is very amenable to genetic analysis, its genome has been sequenced, and because it provides a simple, yet comparable, model of the human nervous system. It is of significance for this project that a number of mutations have been identified that make flies susceptible to epileptic-like seizures. Seizures in the fly are remarkably similar to seizures in humans. Using the genetic tractability of the fly, we hope to identify novel genes that, when mis-regulated, ameliorate seizures and, by doing so, identify new avenues for human drug design.