Professor Linda Greensmith is recognised for her work on the pathophysiology of motor neuron degeneration, in particular in relation to motor neuron disorders (MNDs) such as Amyotrophic Lateral Sclerosis (ALS).
She runs a large multidisciplinary research group at UCL Institute of Neurology, using a wide range of techniques, ranging from whole animal physiology to in vitro models.
Linda’s interest in the neuromuscular system began with her doctoral thesis at UCL, examining the role of neuromuscular interactions in motor neuron development and survival. Between 1989-1996, Linda worked as a Postdoctoral Fellow, firstly at UCL and subsequently at Imperial College, where her research focused on motor neuron degeneration.
In 1996 she was awarded a Wellcome Trust Fellowship to develop her skills in molecular biology and in 1999, Linda was awarded the prestigious Graham Watts Senior Research Fellowship at the UCL Institute of Neurology, funded by a Bequest for MND research. Since establishing the Graham Watts Laboratories, her group has grown and now has an international reputation in the field of MND.
In particular, Linda is internationally recognised for her expertise in mouse models of MND and for undertaking preclinical trials. In 2004, her laboratory made an important contribution to the field, identifying a novel co-inducer of protein chaperones as an effective neuroprotective agent for MND. This work, published in Nature Medicine, has resulted in several international clinical trials. Recent findings from Linda’s lab suggest that this approach, targeting protein chaperones, may also be effective in other protein folding disorders such as the muscle disease Inclusion Body Myopathy (IBM).
More recently, Linda has been developing a novel approach to restore function to paralysed respiratory muscles in MND patients. The approach combines optogenetics and regenerative medicine and uses stem cell-derived grafts of motoneurons that express channelrhodopsin-2, a molecular photo-sensor, to establish neuromuscular junctions with target muscles. Due to the photosensitivity of the graft, muscle contraction can then specifically be triggered by light flashes which are generated by an optical pacemaker device and transmitted to the graft via fiber optic cables. This study was published in 2014 in Science, where it was the subject of a Science Comment (Lyer and Delp, 2014), and chosen by the Science Editorial Team for inclusion in their collection of annotated research papers called “Science in the Classroom”, a new online educational resource.