John Tuthill, Ph.D.

Research

The Tuthill lab will investigate how animals sense the position of their legs and use this spatial information to coordinate their locomotion. To precisely control movement of the limbs, motor circuits must receive and integrate feedback about where our arms and legs are located and how they are moving through space. This feedback is provided by mechanically sensitive proprioceptor neurons embedded throughout the body. Fruit flies, for example, have 152 proprioceptor neurons in the femur of each leg. Feedback from these neurons helps the fly to expertly negotiate unpredictable terrain. By recording the activity of these proprioceptors during controlled leg movements, we found different neuronal subtypes that encode joint position, movement, and direction. Now, we aim to combine genetic and optical methods to monitor and manipulate the activity of leg proprioceptors in walking flies. This work will determine how sensory feedback fine-tunes leg motor control as flies walk on a treadmill, and how perturbation of the proprioceptive system alters the flies’ walking coordination. We will also investigate how proprioception enables adaptive motor plasticity as a fly learns to avoid an obstacle during walking. Because deficits in sensory feedback can lead to a loss of fine motor control, the work could guide therapeutic efforts for sensorimotor disorders or rehabilitation after nerve injury.

As an Innovation Fund investigator, John Tuthill, Ph.D., is teaming up with Sebastian Brauchi, Ph.D., to understand how snow flies continue to function in very cold temperatures. In subzero conditions, ion transport slows and protein movement decreases, jeopardizing the membrane potential and conduction of electrical signals, which are key for neuromuscular function. Yet, snow flies can still move at internal temperatures as low as -10 degrees Celsius. The team will test the hypothesis that snow flies have evolved specific proteins such as more flexible ion channels and pumps, thus allowing them to function at lower temperatures than other insects. The project combines the Tuthill lab’s expertise in insect neurobiology and behavior with the Brauchi lab’s extensive experience studying the biophysical properties of ion channels. Together, they will integrate in vivo electrophysiological recordings, protein sequence analysis, and first-of-their-kind measurements of membrane biophysical properties in subzero conditions to understand how insects have adapted to sustain movement in extreme cold. This work could spark broader investigation of the adaptations of diverse cold-active species.