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Joe Howard, PhD

Eugene Higgins Professor of Molecular Biophysics and Biochemistry and Professor of Physics
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Contact Info

Molecular Biophysics and Biochemistry

P.O. Box 208024

New Haven, CT 06520-8024

United States

About

Titles

Eugene Higgins Professor of Molecular Biophysics and Biochemistry and Professor of Physics

Biography

Jonathon (Joe) Howard is the Eugene Higgins Professor of Molecular Biophysics & Biochemistry, a Professor of Physics, and a member of the Quantitative Biology Institute at Yale University. He is best known for his research on the mechanical properties of motor proteins and the cytoskeleton, and the development of techniques for observing, measuring and manipulating individual biological molecules. His group studies several cellular systems in which force and motion play key roles, including the motility of cilia, and the branching of developing neurons.

Brought up in Australia, where he studied mathematics and neurobiology at the Australian National University, Professor Howard was a professor at the University of Washington Medical School in Seattle, a founding Director of the Max Planck Institute for Molecular Cell Biology and Genetics in Dresden, Germany, before moving to Yale 2013 where he enjoys new research projects and teaching.

Appointments

Education & Training

Postdoctoral Fellow
University of California, San Francisco (1987)
Postdoctoral Fellow
University of Bristol (1985)
PhD
Australian National University, Neurobiology (1983)
BSc (Hon)
Australian National University, Mathematics (1979)

Research

Overview

Motor and Cytoskeletal Systems: From molecules to cells

Tubulin exchange in and out of the microtubule wall and its role in severing, rigidity & dynamics
Microtubules are tubular polymers whose protein subunits, tubulin, associate in a head-to-tail geometry to form protofilaments, thirteen of which form the microtubule’s cylindrical wall. The pipe-like geometry gives the microtubule high rigidity for its protein mass. High bending rigidity is essential for the structural roles that microtubules play in cellular architecture: as tracks for motor proteins such as kinesins and dyneins, and as scaffolds that support force-generating organelles such as the mitotic spindle and the cilium (Howard 2001).

Microtubules grow and shrink by addition and subtraction of tubulin dimers at their ends, processes that are regulated by a host a microtubule associated proteins (Howard and Hyman 2007, Bowne-Anderson et al. 2015). Recently, however, it has become clear that, in addition to removal and addition of tubulin at microtubule ends, significant tubulin exchange also occurs within the wall of the microtubule. Removal can be mediated by microtubule severing enzymes such as spastin and katanin (Kuo & Howard 2021, Kuo et al. 2022), by motor proteins such as kinesins and dyneins, and by mechanical forces applied to the microtubule. Removal of tubulin from the microtubule lattice leads to holes, whose enlargement leads to microtubule softening and eventual breakage, and whose repair by incorporation of new GTP-tubulin from solution can promote microtubule growth. Together, the growth and repair of these defects can profoundly rearrange the microtubule cytoskeleton in cells.

We are developing new techniques for visualizing microtubule defects and to study the kinetic and structural mechanisms of microtubule severing.

Branching morphogenesis of neurons

The architecture of the brain and its constituent neurons is staggeringly complex. This complexity is enabled by the highly branched morphologies of dendrites and axons, which allow each neuron to connect to thousands of other neurons. We recently showed, using Drosophila sensory neurons as a model system, that the branching, growth, and retraction of dendrite tips can generate many of the morphological features of dendrites including the rate of growth of their arbors during development, and the average length, density, and orientation of their branches (Shree et al. 2022, Ouyang et al. in preparation). Branch diameters, another important morphological feature of neurons, change systematically across branch points, which facilitates the distribution of materials and nutrients through the network (Liao et al. 2019). Furthermore, neuronal dendrites have a scale-invariant network architecture that optimizes their function and metabolism (Liao et al. 2023).

Currently, we are using genetic perturbations and high-resolution imaging to elucidate the role of the microtubule cytoskeleton in generating dendrite morphology.

The motility of cilia and flagella

A major open question in cell motility is how the dynein motors, which power the bending of cilia and flagella, are coordinated to give the periodic beating patterns that drive cell motion (Howard et al. 2022). We are using the single-celled alga Chlamydomonas reinhardtii as a model system to test different models of motor coupling (Geyer et al. 2016, Sartori et al. 2016, Geyer 2022).

Currently, we are analyzing waveforms of different mutants by high-speed light microscopy and high-resolution electron cryo-microscopy.

Medical Subject Headings (MeSH)

Biophysics; Cilia; Developmental Biology; Microtubules; Mitosis; Molecular Motor Proteins; Nanotechnology; Neurobiology; Physics

Research at a Glance

Yale Co-Authors

Frequent collaborators of Joe Howard's published research.

Publications

2023

2022

2021

Academic Achievements & Community Involvement

  • activity

    Biophysical Journal

  • activity

    Physics of Life

  • activity

    Biophysical Society

  • activity

    American Physical Society

  • activity

    American Society for Cell Biology

Get In Touch

Contacts

Academic Office Number
Mailing Address

Molecular Biophysics and Biochemistry

P.O. Box 208024

New Haven, CT 06520-8024

United States

Administrative Support

Locations

  • Jonathon Howard

    Academic Office

    Sterling Hall of Medicine

    333 Cedar Street, Wing C, Fl 1, Rm SHM C-130A

    New Haven, CT 06510

  • HowardLab

    Lab

    Sterling Hall of Medicine

    333 Cedar Street, Wing C, Fl 1, Rm SHM C-130

    New Haven, CT 06510

    Business Office

    203.432.5587