An investigating into the effect of acute and chronic KATP channel modulation on membrane conductance and cellular metabolism

本博士项目的工作将以诱导多能干细胞来源的神经细胞的功能评估为基础。评估的主要方法将涉及单细胞膜片钳电生理的多个方面。这将支持额外的工作，使用多电极阵列和实时细胞成像。该项目将研究在单层培养和基于肽水凝胶的新型3D培养中生长的神经元。也将有机会参与到基于所收集数据的神经元特性的数学建模中。我们将提供所需的所有细胞培养和神经生理学方法的全面培训。对单个神经元兴奋性机制的理解将基于药理学干预和适当的分子方法。与阿斯利康神经科学家合作，我们还将研究人类神经元的兴奋性是如何通过从他们的发现组合中选择药物靶点来改变的。

The work in this doctoral project will be based around functional assessments of neural cells derived from inducible pluripotent stem cell sources. The major methods of assessment will involve multiple aspects of single cell patch clamp electrophysiology. This will be supported with additional work using multielectrode arrays and real time cellular imaging. The project will investigate neurons grown both in monolayer cultures and in novel 3D cultures based on peptide hydrogels. There will also be opportunities to become involved in mathematically modelling neuronal properties based on the data gathered. We will provide full training in all the cell culture and neurophysiological methods required. Understandings of the mechanisms underpinning excitability of single neurones will be based on pharmacological interventions and where appropriate molecular methods. Working with AstraZeneca neuroscientists we will also investigate how human neuronal excitability is modified by selected druggable targets from within their discovery portfolio.