Development of drug screening platforms for central nervous system regeneration

点击翻译按钮获取中文摘要

Numerous neurological disorders are characterized by damage to the insulation surrounding nerve fibres, termed myelin, leading to nerve damage/ loss and cognitive, motor, and sensory deficits. Although myelin can be regenerated, this process often fails in disease (for example in cerebral palsy or progressive MS), and no therapies are currently approved to enhance this process. Identifying drug targets to develop new therapies is challenging, as the mechanisms underpinning successful regeneration of myelin are not well understood.Thus, the most rapid route to identifying pro-regenerative therapies is to screen drugs that have been approved for other indications. However, no platform currently exists for efficient screening of drugs in the injured mammalian brain without the use of a large number of experimental animals.This PhD project will develop a screening platform that will allow for the first unbiased drug screen in injured mammalian brain specifically for regenerative drugs suitable for repurposing. The project will involve combining established brain explant models of brain injury with automated live-imaging and analyses to carry out a drug screen for myelin regeneration. This involves the use of transgenic animals, cell culture, live imaging, confocal microscopy, setting up imaging analyses pipelines, 3D printing, experimental design and statistical analyses. This approach will also serve as a proof-of-concept study for automated organ explant screening, and identify a drug that may eventually lead to a clinical trial for myelin regeneration. The focus of this lab, based at The Queen's Medical Research Institute in the MRC Centre for Reproductive Health, is to understand the cellular and molecular mechanisms regulating myelin regeneration and to identify new therapeutic strategies to support this process in disease. The lab is composed of the PI, a PhD student, 2 postdocs, and a research assistant. The student will be integrated into the Edinburgh Neuroscience program and the Edinburgh Centre for MS Research, and will participate in lab meetings from groups with shared research interests, local conferences/meetings, and international conferences.