Characterisation of seizure-suppressor genes in Drosophila

果蝇癫痫抑制基因的表征

• 批准号: BB/E000029/1
• 负责人: Richard Baines
• 金额: $ 37.27万
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2007
• 资助国家: 英国
• 起止时间: 2007 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FE000029%2F1
• 关键词: Characterisation; seizure; suppressor; genes; Drosophila

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.

哺乳动物中枢神经系统由许多不同类型的神经细胞组成。这些细胞在接触的目标上有所不同，信号化学物质（神经递质）释放的方式以及它们能够发射触发神经递质（S）的电势的电势。神经元功能的任何这些方面的异常都可以导致神经系统疾病，包括但不限于精神分裂症，抑郁和癫痫。因此，隐含的是，为了为神经系统疾病设计更好，更有效的治疗方法，需要充分理解潜在的原因。癫痫病是一个很好的例子。目前，只有约70％的患者对药物治疗有反应；其余30％没有。显然需要其他药物。但是，在设计新药之前，首先需要鉴定新的靶分子。只有在鉴定之后才能设计药物来与此类分子相互作用并作用。为此，我们使用的是果蝇果蝇果蝇，因为它非常适合遗传分析，因此已经对其基因组进行了测序，并且由于它提供了人类神经系统的简单但可比的模型。对于该项目而言，已经确定了许多突变使苍蝇易受癫痫样癫痫发作。飞行中的癫痫发作与人类的癫痫发作非常相似。使用苍蝇的遗传障碍性，我们希望识别出新的基因，当错误调节时，可以改善癫痫发作，并通过这样做确定人类药物设计的新途径。