Jonathon Howard

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Jonathon Howard
NationalityAustralian, USA
Alma materAustralian National University
Known forResearch in single-molecule biophysics of motor proteins, cytoskeleton, cell shape and motion
SpouseKarla Neugebauer
ChildrenOlivia Howard and Peter Neugebauer
Scientific career
ThesisKinetics and noise of transduction in insect photoreceptors (1982)
Doctoral advisorAllan Snyder, Simon Laughlin
Websitehttps://howardlab.yale.edu

Jonathon Howard is a biophysicist and cell biologist. He is the Eugene Higgins Professor of Molecular Biophysics & Biochemistry and a Professor of Physics at Yale University. His research is focused on microtubules, motor proteins and cell shape and motion.

Education

Howard was educated at Australian National University, where he received a B.A. degree in Pure Mathematics in 1979 and a Ph.D. in Neurobiology in 1983.[1] His thesis is titled Kinetics and noise of transduction in insect photoreceptors, and his supervisors were Allan Snyder and Simon Laughlin.[2]

Research

During his PhD, he worked with Simon Laughlin, who is an experimentalist, and Allan Snyder, who is a theoretician, on the optics and electrophysiological properties of the fly compound eye.

During his postdoc with A. James Hudspeth at University of California, San Francisco, he made several major contributions ranging from hair cells to motor proteins. He developed very precise mechanical techniques to study how hair cells of the vertebrate inner ear detect sound and acceleration.[3] and confirmed the “gating spring” model, proposed by Corey and Hudspeth. He also discovered that hair cells adapt to sustained stimuli via a mechanical mechanism in which an active process, which he hypothesized to be driven by the motor protein myosin-1, regulates the tension in the gating spring.[4] During this period, he also collaborated with Ronald Vale, and developed the first single-molecule assay for studying motor proteins. His work showed that kinesin moves processively, taking several hundred steps along a microtubule before dissociating.[5] This finding explained how kinesin could carry cargos long distances in the axons of nerve cells. This work also helped to establish the field of single-molecule biophysics.

In 1989, Howard set up his own lab at the University of Washington, where his research focused on how motor proteins convert chemical energy derived from the hydrolysis of ATP into mechanical work used to drive cell motility. His research contributes to our understanding of motor protein and microtubule in the following ways:[6] his group

  • measured the force generated by a single kinesin molecule, ~5 pN.[7]
  • showed that kinesin moves on a path parallel to the protofilaments and measured the dependence of the speed of movement of kinesin on the load force[8]
  • determined that each kinesin hydrolyzing exactly one molecule of ATP for each 8-nm step that it takes along the surface of the microtubule[9]

In 2000, Howard moved to Germany, where he played a key role, as Director, in establishing the Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG) in Dresden, one of the foremost biological research institutes in Europe. At the MPI-CBG, research in the Howard lab focused on:

In 2013, Howard became the Eugene Higgins Professor of Molecular Biophysics and Biochemistry at Yale University. At Yale, he has continued his interest in the biophysics of the microtubule skeleton, including studies of the microtubule-severing proteins Spastin,[16] spindle localization in the C. elegans embryo,[17] ciliary beating in Chlamydomonas,[18] physical bioenergetics during Zebrafish embryogenesis[19] and branching morphogenesis of neuronal dendrites.[20][21]

Howard summarized many results and ideas on molecular motors in a monograph Mechanics of Motor Proteins and the Cytoskeleton,[22][23][24] which has sold over 5,000 copies and been cited more than 3,000 times.

Awards and honors

  • Fellow of the Biophysical Society (2017)[25]
  • Pioneer Award, National Institutes of Health (2015)[26]
  • Member, European Molecular Biology Organization (2004)[27]
  • John Simon Guggenheim Fellow (1996)[28]
  • Pew Scholar, Program in the Biomedical Sciences (1990)[29]

References

  1. ^ Novak, Steven J. "Oral history interview with Jonathon Howard". Science History Institute Digital Collections. Retrieved 2023-05-20.
  2. ^ Howard, Jonathon (1982). Kinetics and noise of transduction in insect photoreceptors (Thesis). Australian National University. OCLC 222145173.
  3. ^ Howard, J.; Hudspeth, A. J. (1988). "Compliance of the hair bundle associated with gating of mechanoelectrical transduction channels in the Bullfrog's saccular hair cell". Neuron. 1 (3): 189–199.
  4. ^ Howard, J.; Hudspeth, A. J. (1987). "Mechanical relaxation of the hair bundle mediates adaptation in mechanoelectrical transduction by the bullfrog's saccular hair cell". Proceedings of the National Academy of Sciences. 84 (9): 3064–3068.
  5. ^ Howard, J.; Hudspeth, A. J.; Vale, R. D. (1989). "Movement of microtubules by single kinesin molecules". Nature. 342: 154–158.
  6. ^ Sedwick, Caitlin (2014). "Jonathon Howard: Motor proteins go walkabout". Journal of Cell Biology. 204 (2): 150–151.
  7. ^ Hunt, A. J.; Gittes, F.; Howard, J. (1994). "The force exerted by a single kinesin molecule against a viscous load". Biophysical Journal. 67 (2): 766–781.
  8. ^ Ray, S.; Milligan, R. A.; Howard, J. (1993). "Kinesin follows the microtubule's protofilament axis". J. Cell Biol. 121 (5): 1083–1093.
  9. ^ Coy, D. L.; Hancock, W. O.; Wagenbach, M.; Howard, J. (1999). "Kinesin's tail domain is an inhibitory regulator of the motor domain". Nat. Cell Biol. 1: 288–292.
  10. ^ Helenius, J.; Brouhard, G.; Kalaidzidis, Y; Diez, S; Howard, J. (2006). "The depolymerizing kinesin MCAK uses lattice diffusion to rapidly target microtubule ends". Nature. 441: 115–119.
  11. ^ Varga, V.; Helenius, J.; Tanaka, K.; Hyman, A. A.; Tanaka, T. U.; Howard, J. (2006). "Yeast kinesin-8 depolymerizes microtubules in a length-dependent manner". Nat. Cell Biol. 8: 957–962.
  12. ^ Brouhard, G. J.; Stear, J. H.; Noetzel, T. L.; Al-Bassam, J.; Kinoshita, K.; Harrison, S. C.; Howard, J.; Hyman, A. A. (2008). "XMAP215 is a processive microtubule polymerase". Cell. 132 (1): 79–88.
  13. ^ Riedel‐Kruse, I. H.; Hilfinger, A.; Howard, J.; Jülicher, F. (2007). "How molecular motors shape the flagellar beat". HFSP Journal. 1: 192–208.
  14. ^ Howard, J.; Bechstedt, S. (2004). "Hypothesis: A helix of ankyrin repeats of the NOMPC-TRP ion channel is the gating spring of mechanoreceptors". Curr. Biol. 14 (6): R224–R226.
  15. ^ Riedel, I. H.; Kruse, K.; Howard, J. (2005). "A Self-Organized Vortex Array of Hydrodynamically Entrained Sperm Cells". Science. 309 (5732): 300–303.
  16. ^ Kuo, Y.-W.; Trottier, O.; Mahamdeh, M.; Howard, J. (2019). "Spastin is a dual-function enzyme that severs microtubules and promotes their regrowth to increase the number and mass of microtubules". Proceedings of the National Academy of Sciences. 116 (12): 5533–5541.
  17. ^ Garzon-Coral, C.; Fantana, H. A.; Howard, J. (2016). "A force-generating machinery maintains the spindle at the cell center during mitosis". Science. 352 (6289): 1124–1127.
  18. ^ Sartori, P.; Geyer, V. F.; Scholich, A.; Jülicher, F.; Howard, J. (2016). "Dynamic curvature regulation accounts for the symmetric and asymmetric beats of Chlamydomonas flagella". eLife. 5: e13258.
  19. ^ Rodenfels, J.; Neugebauer, K. M.; Howard, J. "Heat Oscillations Driven by the Embryonic Cell Cycle Reveal the Energetic Costs of Signaling". Developmental Cell. 48 (5): 646–658.
  20. ^ Liao, M. J.; Liang, X.; Howard, J. (2021). "The narrowing of dendrite branches across nodes follows a well-defined scaling law". Proceedings of the National Academy of Sciences. 118 (27): e2022395118.
  21. ^ Shree, S.; Sutradhar, S.; Trottier, O.; Tu, Y.; Liang, X.; Howard, J. (2022). "Dynamic instability of dendrite tips generates the highly branched morphologies of sensory neurons". Sci. Adv. 8 (26): eabn0080.
  22. ^ Howard, J. (2001). Mechanics of Motor Proteins and the Cytoskeleton. Sinauer Associates. ISBN 978-0878933334.
  23. ^ Mogilner, Alex (2002). "Mechanics of Motor Proteins and the Cytoskeleton". Physics Today. 55 (3): 63–64.
  24. ^ Schmitz, Stephan; Veigel, Claudia (2002). "Size matters: Mechanics of Motor Proteins and the Cytoskeleton". J Cell Sci. 115 (14): 2807–2808.
  25. ^ "Joe Howard honored as 2017 Fellow of the Biophysical Society | Molecular Biophysics and Biochemistry". mbb.yale.edu. Retrieved 2022-11-08.
  26. ^ "NIH Director's Pioneer Award Program – 2015 Award Recipients". commonfund.nih.gov. 2018-09-18. Retrieved 2022-11-08.
  27. ^ "Find people in the EMBO Communities". people.embo.org. Retrieved 2022-11-08.
  28. ^ "Jonathon Howard". John Simon Guggenheim Memorial Foundation. Retrieved 2022-11-08.
  29. ^ Pew Biomedical Scholars. "Jonathon Howard, Ph.D." Pew Biomedical Scholars. Retrieved 2022-11-08.
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