Neurons use their axons for direct communication with other cells. These axons are constantly challenged by the surrounding environment, and they also have to battle the rigors of aging. Axonal maintenance throughout life is a major cell biological & bioenergetic challenge for the neuron; and essential, as axons ensure continued circuit function. Any disturbance ultimately results in axon degeneration, which is a hallmark of nervous system injury and neurodegenerative disease. However, we know surprisingly little about why or how axons undergo degeneration. Our present focus lies in the molecular mechanisms that (1) ensure the survival of the axon, (2) execute the degeneration thereof, and (3) promote neurodegeneration of circuit-integrated neurons.
We use the fruit fly Drosophila to gain insights into the above questions: it offers an array of unparalleled powerful in vivo tools to analyze gene function, dissect molecular mechanisms, observe cellular biology, study behavior, and perform unbiased forward genetic screens. We are able to take advantage of state-of-the-art genetics, visual resolution with previously unprecedented depth, side-by-side manipulation of neurons and glia, optogenetics, and in vivo pulldowns. We are capable to manipulate distinct neurons that contain the longest axons in the fly: sensory neurons in the wing, and motor neurons in the leg. Our approaches may ultimately help to uncover mechanisms of a variety of distinct neurological conditions, as the mechanisms of axonal/neuronal stability are evolutionarily conserved from flies to mammals.