Jonathon Howard, Ph.D.

Research

The Howard laboratory is interested in how cells get their shapes and how their shapes change as cells develop, divide, and move. Our research focuses on the biochemistry and biophysics of the cytoskeleton, particularly emphasizing the mechanics of microtubules and microtubule-based motor proteins. On the one hand, the lab is interested in how these proteins work: How do kinesins, dyneins, and spastins act as molecular machines to convert chemical energy derived from the hydrolysis of adenosine triphosphate (ATP) into mechanical work used to move along, bend, depolymerize, or sever microtubules? On the other hand, the lab is interested in the roles that microtubules and their motors play in shaping and moving cells. A major focus is on neuronal morphology, especially the cytoskeletal mechanisms underlying branching and growth in dendrites. The lab also has a strong interest in ciliary and flagellar motility, specifically how dynein motors coordinate to drive periodic beating patterns. We approach these questions using a combination of high-resolution microscopy, single-molecule in vivo imaging, theory, and computation. We use the fruit fly as a model organism, as well as primitive animals such as Hydra and Nematostella, and make use of extensive morphological and connectomic databases.

As an Innovation Fund investigator, Jonathon Howard, Ph.D., is teaming up with Tomás Falzone, Ph.D., to uncover how the diameters of both dendrites and axons support the demands of optimal neuronal function. Neurons are key communicators within the body, transmitting electrical signals to and within the brain. Dendrites are branched processes that extend from the cell bodies of neurons and collect inputs from other neurons and the environment. At the same time, axons are long and thin processes that send these signals from the cell body to other neurons. The researchers hypothesize that neuronal diameters are regulated by cytoskeletal structures and intracellular transport. By drawing on Howard’s expertise in dendritic morphology and high-resolution microscopy and on Falzone’s extensive experience in axonal transport and the development of human neuronal models, the team aims to answer this fundamental question regarding neuronal shape. Insights from this collaboration could reveal new knowledge about neuronal development, biology, and function and provide crucial information about how these morphological processes can be disrupted in neurodegenerative disorders associated with branching defects and neurite swelling.