Professor Robin Franklin, University of Cambridge
Dr Amnon Buxboim, The Hebrew University of Jerusalem
The brain and spinal cord (collectively referred to as the central nervous system or CNS) is comprised of nerve cells (neurons) whose fibres (axons) form an extraordinarily complex network which enables us to perform many of the functions that make us human. The axons are assisted in their tasks by an insulating layer that wraps around the nerve fibre called a myelin sheath. The myelin sheath, which is made and maintained by a cell called the oligodendrocyte, has two roles: to facilitate the communication between neurons by way of electrical signals passed along the axon, and to protect axons by keeping them intact and healthy.
New oligodendrocytes are generated in the adult CNS by stem cells that are abundant throughout the CNS. This occurs as part of the normal human growth and also in diseases which involve the loss of oligodendrocytes and the myelin sheath, of which multiple sclerosis (MS) is the best-known example. The regeneration of oligodendrocytes by CNS stem cells in called remyelination. However, as with all regenerative processes, the remyelination becomes increasingly less efficient with ageing, which in a chronic disease such as MS means that eventually a point is reached when the exposed axons die. This is an irreversible loss that is called neurodegeneration.
A major reason for the age-related decline in remyelination is the effects of age on CNS stem cells, which become increasingly less able to fulfil their normal roles as we progress through adult life. It has recently been found that these age-related changes occur in CNS stem cells because the brain increases in stiffness as we age. CNS stem cells, are acutely sensitive to the physical features of the ageing brain.
In this project, Professor Franklin and Professor Buxboim ask how a stiff brain is able to induce disadvantageous changes in adult CNS stem cells, and how are the physical signals of the brain transmitted to a CNS stem cell to change its function. These are important questions since the answers will provide clues as to how the effects of age might be reversed therapeutically.
The project will combine the distinctive but complementary expertise of Professor Franklin, who is an expert in the biology of CNS stem cell, His co-PI Dr Kevin Chalut in the physics of stem cells and Professor Buxboim in how mechanical signals change the function of cells.