STEM ZAP · Optogenetics based discovery of new pathways towards stem-cell mediated myelin repair

Optogenetics based discovery of new pathways towards stem-cell mediated myelin repair

This project aimed to identify novel molecular mechanisms involved in the process of myelination, which could be used to promote myelin repair in the central nervous system (CNS). This work is both timely and important as injury to myelin, the insulating material that ensures efficient electrical signal transmission in the brain, causes neurological disability in an estimated 405,000 Multiple Sclerosis (MS) patients in the EU at a cost of €14.6 billion per year to the economy. Therefore, new therapies that repair damaged myelin are an important clinical ambition, whose resolution could deliver enormous health and economic benefits across Europe. CNS Myelin is formed from oligodendrocytes (OL) that develop (differentiate) from specialized precursor cells known as OL precursor cells (OPC). This process involves the activation of pro-developmental genes, which could, if they were identified, be targeted to promote myelin repair. In this project we aimed to use a new technology known as optogenetics to stimulate OPC and induce them to develop into OL. Optogenetics involves the use of specialized proteins (Channel Rhodopsin 2 aka ChR2) derived from green algae that, when stimulated with blue light, enables positive currents to flow into the host cell. The positive current depolarizes the cell membrane leading to powerful changes in the cells activity. In some precursor cells membrane depolarization promotes differentiation, thus we reasoned that membrane depolarization would prove a useful means to maximize the development of OPC and identify new genes involved in myelin formation. The main objectives of this work we therefore to: 1. Genetically engineer OPC to produce ChR2 molecules (ChR2-OPC) and test the ability of membrane depolarization (via blue light stimulation) to promote the differentiation of these cells into oligodendrocytes. 2. Use a sequencing approach to identify the genes that are activated in ChR2-OPC following membrane depolarization. 3. Test a set of these newly identified genes in laboratory experiments designed to test OPC diffentiation and myelination. 4. Study post mortem MS brain tissue to determine if there are links between the newly identified genes and OPC located in damaged and diseased areas of the brain (lesions). OPC often fail to differentiate in areas with MS damage, thus the new OPC genes, if found to be altered in lesions, may provide interesting new targets for further research.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз