Jonathon (Joe) 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.[1] 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.Sc. degree (with honors) in Pure Mathematics in 1979 and a Ph.D. in Neurobiology in 1983.[2] His Ph.D. thesis is titled Kinetics and noise of transduction in insect photoreceptors, and his supervisors were Allan Snyder and Simon Laughlin.[3]
Career and 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 to the understanding of hair cells and motor proteins. He developed very precise mechanical techniques to study how hair cells of the vertebrate inner ear detect sound and acceleration.[4] 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.[5] 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.[6] 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:[7] his group
measured the force generated by a single kinesin molecule, ~5 pN.[8]
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[9]
determined that each kinesin hydrolyzing exactly one molecule of ATP for each 8-nm step that it takes along the surface of the microtubule[10]
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.[11] 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.[18]
At Yale, he has continued his interest in the biophysics of the microtubule skeleton, including studies of the microtubule-severing proteins Spastin, spindle localization in the C. elegans embryo,[19] ciliary beating in Chlamydomonas,[20] physical bioenergetics during Zebrafish embryogenesis[21] and branching morphogenesis of neuronal dendrites.[22][23]
Howard summarized many results and ideas on molecular motors in a monograph Mechanics of Motor Proteins and the Cytoskeleton,[24][25][26] which has sold over 5,000 copies and been cited more than 3,000 times.
^Howard, Jonathon (1982). Kinetics and noise of transduction in insect photoreceptors (Thesis). Australian National University. OCLC222145173.
^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. doi:10.1016/0896-6273(88)90139-0. PMID2483095.
^Howard, J.; Hudspeth, A. J.; Vale, R. D. (1989). "Movement of microtubules by single kinesin molecules". Nature. 342 (6246): 154–158. doi:10.1038/342154a0. PMID2530455.
^Ray, S.; Milligan, R. A.; Howard, J. (1993). "Kinesin follows the microtubule's protofilament axis". J. Cell Biol. 121 (5): 1083–1093. doi:10.1083/jcb.121.5.1083.
^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 (5): 288–292. doi:10.1038/13001. PMID10559941.
^"Former Directors". Max Planck Institute of Molecular Cell Biology and Genetics.
^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 (7089): 115–119. doi:10.1038/nature04736. PMID16672973.
^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 (9): 957–962. doi:10.1038/ncb1462.
