Investigating metabolic dysfunction as a driver of Motor Neuron Disease

重要的研究工作增加了我们对支持ALS病理学的细胞功能障碍的理解，但我们还有很多东西要学。最近的研究结果表明，代谢缺陷在ALS的发病和进展中起着重要作用，为新的治疗途径提供了诱人的前景。我们已经开发了一种快速高通量的ALS酵母模型，使我们能够探测与蛋白质超氧化物歧化酶1（Sod 1）缺陷相关的细胞毒性的代谢性质。Sod 1的突变导致家族性ALS，也与该疾病的散发形式有关。该项目将使用酵母系统以高分辨率建立与ALS患者中发现的Sod1突变相关的代谢缺陷，并将这些发现转化为从ALS患者中分离的人类细胞。该项目是多学科的，在坎贝尔Gourlay博士（肯特）和Majid Hafezparast教授（苏塞克斯）的实验室内提供广泛的尖端细胞生物学、微生物学、计算和生物化学技术的培训。这项研究的结果将导致我们对与ALS相关的代谢功能障碍的理解显着增加。

Significant research efforts have increased our understanding of the cellular dysfunction that underpins ALS pathology, but we have much to learn. Recent findings suggest that metabolic defects play an important role in the onset and progression of ALS, offering the tantalising prospect of new avenues to therapy. We have developed a rapid high throughput yeast model of ALS that enables us to probe the metabolic nature of cellular toxicity associated with defects in the protein Superoxide dismutase 1 (Sod1). Mutations in Sod1 lead to familial ALS and are also linked to sporadic forms of the disease. The project will establish the metabolic defects associated with Sod1 mutations found in ALS patients at high resolution using the yeast system and translate these findings into human cells isolated from ALS patients. The project is multi-disciplinary and offers training in a wide range of cutting edge cell biological, microbiological, computational and biochemical techniques within the labs of Dr. Campbell Gourlay (Kent) and Prof. Majid Hafezparast (Sussex). The outcomes of this research will lead to a significant increase in our understanding of the metabolic dysfunction associated with ALS.