Richard Tuxworth is a cell biologist interested in disorders of the nervous system. He studies both early-onset inherited forms of neurodegeneration caused by lysosomal dysfunction and aspects of the common neurodegenerative disorders associated with old age.
Lysosomal storage disorders and neural development
Lysosomes are low-pH organelles critical for recycling in cells and for coordination of growth and stress signaling. Lysosomes become dysfunctional in a large group of inherited syndromes known as the lysosomal storage disorders. Many result in neuropathology at a young age, including fatal childhood-onset neurodegeneration. The early pathology suggests lysosomal function must be essential for normal neuronal development. To study this, Richard’s group primarily use fruit flies as a simple model system because the flies can be rapidly manipulated genetically to mirror some of the changes seen in the human lysosomal storage disorders.
These models are then used to ask what happens to neural development when lysosomal function is impaired and to assess the consequences for nervous system function. This approach combines genetics, cell biology, neurobiology and imaging with cell-based studies and proteomics.
The cell biology of neurodegeneration
Common late-onset neurodegenerative disorders such as Alzheimer’s disease are an increasing burden on the health services and more generally society as the population ages. There are no currently effective methods of slowing disease progression. Richard and colleagues in the College of Medical and Dental Sciences are investigating novel methods of intervening in neurodegenerative disorders to relieve disease burden. Richard’s group uses simple models of neurodegenerative disease developed in fruit flies to perform rapid surveys of potential new methods of intervention. Successful methods can then be validated in other systems.