Jonathon Howard

Last updated
Jonathon Howard
Joe howard at yale.jpg
NationalityAustralian, USA
Alma mater Australian 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
Thesis Kinetics and noise of transduction in insect photoreceptors  (1982)
Doctoral advisor Allan Snyder, Simon Laughlin
Website https://howardlab.yale.edu

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.

Contents

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

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.

Awards and honors

Related Research Articles

<span class="mw-page-title-main">Microtubule</span> Polymer of tubulin that forms part of the cytoskeleton

Microtubules are polymers of tubulin that form part of the cytoskeleton and provide structure and shape to eukaryotic cells. Microtubules can be as long as 50 micrometres, as wide as 23 to 27 nm and have an inner diameter between 11 and 15 nm. They are formed by the polymerization of a dimer of two globular proteins, alpha and beta tubulin into protofilaments that can then associate laterally to form a hollow tube, the microtubule. The most common form of a microtubule consists of 13 protofilaments in the tubular arrangement.

<span class="mw-page-title-main">Cytoskeleton</span> Network of filamentous proteins that forms the internal framework of cells

The cytoskeleton is a complex, dynamic network of interlinking protein filaments present in the cytoplasm of all cells, including those of bacteria and archaea. In eukaryotes, it extends from the cell nucleus to the cell membrane and is composed of similar proteins in the various organisms. It is composed of three main components: microfilaments, intermediate filaments, and microtubules, and these are all capable of rapid growth or disassembly depending on the cell's requirements.

<span class="mw-page-title-main">Spindle apparatus</span> Feature of biological cell structure

In cell biology, the spindle apparatus is the cytoskeletal structure of eukaryotic cells that forms during cell division to separate sister chromatids between daughter cells. It is referred to as the mitotic spindle during mitosis, a process that produces genetically identical daughter cells, or the meiotic spindle during meiosis, a process that produces gametes with half the number of chromosomes of the parent cell.

<span class="mw-page-title-main">Kinesin</span> Eukaryotic motor protein

A kinesin is a protein belonging to a class of motor proteins found in eukaryotic cells. Kinesins move along microtubule (MT) filaments and are powered by the hydrolysis of adenosine triphosphate (ATP). The active movement of kinesins supports several cellular functions including mitosis, meiosis and transport of cellular cargo, such as in axonal transport, and intraflagellar transport. Most kinesins walk towards the plus end of a microtubule, which, in most cells, entails transporting cargo such as protein and membrane components from the center of the cell towards the periphery. This form of transport is known as anterograde transport. In contrast, dyneins are motor proteins that move toward the minus end of a microtubule in retrograde transport.

In cell biology, microtubule-associated proteins (MAPs) are proteins that interact with the microtubules of the cellular cytoskeleton. MAPs are integral to the stability of the cell and its internal structures and the transport of components within the cell.

Cell migration is a central process in the development and maintenance of multicellular organisms. Tissue formation during embryonic development, wound healing and immune responses all require the orchestrated movement of cells in particular directions to specific locations. Cells often migrate in response to specific external signals, including chemical signals and mechanical signals. Errors during this process have serious consequences, including intellectual disability, vascular disease, tumor formation and metastasis. An understanding of the mechanism by which cells migrate may lead to the development of novel therapeutic strategies for controlling, for example, invasive tumour cells.

<span class="mw-page-title-main">Molecular motor</span> Biological molecular machines

Molecular motors are natural (biological) or artificial molecular machines that are the essential agents of movement in living organisms. In general terms, a motor is a device that consumes energy in one form and converts it into motion or mechanical work; for example, many protein-based molecular motors harness the chemical free energy released by the hydrolysis of ATP in order to perform mechanical work. In terms of energetic efficiency, this type of motor can be superior to currently available man-made motors. One important difference between molecular motors and macroscopic motors is that molecular motors operate in the thermal bath, an environment in which the fluctuations due to thermal noise are significant.

<span class="mw-page-title-main">Motor protein</span> Class of molecular proteins

Motor proteins are a class of molecular motors that can move along the cytoskeleton of cells. They convert chemical energy into mechanical work by the hydrolysis of ATP. Flagellar rotation, however, is powered by a proton pump.

<span class="mw-page-title-main">KIF23</span> Protein-coding gene in the species Homo sapiens

Kinesin-like protein KIF23 is a protein that in humans is encoded by the KIF23 gene.

<span class="mw-page-title-main">KIF5B</span> Protein-coding gene in the species Homo sapiens

Kinesin family member 5B (KIF5B) is a protein that in humans is encoded by the KIF5B gene. It is part of the kinesin family of motor proteins.

<span class="mw-page-title-main">KIF3A</span> Protein-coding gene in the species Homo sapiens

Kinesin-like protein KIF3A is a protein that in humans is encoded by the KIF3A gene.

<span class="mw-page-title-main">KIFC1</span> Protein-coding gene in the species Homo sapiens

Kinesin-like protein KIFC1 is a protein that in humans is encoded by the KIFC1 gene.

<span class="mw-page-title-main">KIF17</span> Protein-coding gene in the species Homo sapiens

Kinesin-like protein KIF17 is a protein that in humans is encoded by the KIF17 gene. KIF17 and its close relative, C. elegans OSM-3, are members of the kinesin-2 family of plus-end directed microtubule-based motor proteins. In contrast to heterotrimeric kinesin-2 motors, however, KIF17 and OSM-3 form distinct homodimeric complexes. Homodimeric kinesin-2 has been implicated in the transport of NMDA receptors along dendrites for delivery to the dendritic membrane, whereas both heterotrimeric and homodimeric kinesin-2 motors function cooperatively in anterograde intraflagellar transport (IFT) and cilium biogenesis.

<span class="mw-page-title-main">Kinesin-like protein KIF11</span> Protein-coding gene in the species Homo sapiens

Kinesin-like protein KIF11 is a molecular motor protein that is essential in mitosis. In humans it is coded for by the gene KIF11. Kinesin-like protein KIF11 is a member of the kinesin superfamily, which are nanomotors that move along microtubule tracks in the cell. Named from studies in the early days of discovery, it is also known as Kinesin-5, or as BimC, Eg5 or N-2, based on the founding members of this kinesin family.

<span class="mw-page-title-main">Ronald Vale</span> American biochemist

Ronald David Vale ForMemRS is an American biochemist and cell biologist. He is a professor at the Department of Cellular and Molecular Pharmacology, University of California, San Francisco. His research is focused on motor proteins, particularly kinesin and dynein. He was awarded the Canada Gairdner International Award for Biomedical Research in 2019, the Shaw Prize in Life Science and Medicine in 2017 together with Ian Gibbons, and the Albert Lasker Award for Basic Medical Research in 2012 alongside Michael Sheetz and James Spudich. He is a fellow of the American Academy of Arts and Sciences and a member of the National Academy of Sciences. He was the president of the American Society for Cell Biology in 2012. He has also been an investigator at the Howard Hughes Medical Institute since 1995. In 2019, Vale was named executive director of the Janelia Research Campus and a vice president of HHMI; his appointment began in early 2020.

<span class="mw-page-title-main">KIF15</span> Protein-coding gene in the species Homo sapiens

Kinesin family member 15 is a protein that in humans is encoded by the KIF15 gene.

<span class="mw-page-title-main">Neurotubule</span>

Neurotubules are microtubules found in neurons in nervous tissues. Along with neurofilaments and microfilaments, they form the cytoskeleton of neurons. Neurotubules are undivided hollow cylinders that are made up of tubulin protein polymers and arrays parallel to the plasma membrane in neurons. Neurotubules have an outer diameter of about 23 nm and an inner diameter, also known as the central core, of about 12 nm. The wall of the neurotubules is about 5 nm in width. There is a non-opaque clear zone surrounding the neurotubule and it is about 40 nm in diameter. Like microtubules, neurotubules are greatly dynamic and the length of them can be adjusted by polymerization and depolymerization of tubulin.

Casper Hoogenraad is a Dutch Cell Biologist who specializes in molecular neuroscience. The focus of his research is the basic molecular and cellular mechanisms that regulate the development and function of the brain. As of January 2020, he serves as Vice President of Neuroscience at Genentech Research and Early Development.

Edwin W. Taylor is an adjunct professor of cell and developmental biology at Northwestern University. He was elected to the National Academy of Sciences in 2001. Taylor received a BA in physics and chemistry from the University of Toronto in 1952; an MSc in physical chemistry from McMaster University in 1955, and a PhD in biophysics from the University of Chicago in 1957. In 2001 Taylor was elected to the National Academy of Scineces in Cellular and Developmental Biology and Biochemistry.

J. Richard McIntosh is a Distinguished Professor Emeritus in Molecular, Cellular, and Developmental Biology at the University of Colorado Boulder. McIntosh first graduated from Harvard with a BA in Physics in 1961, and again with a Ph.D. in Biophysics in 1968. He began his teaching career at Harvard but has spent most of his career at the University of Colorado Boulder. At the University of Colorado Boulder, McIntosh taught biology courses at both the undergraduate and graduate levels. Additionally, he created an undergraduate course in the biology of cancer towards the last several years of his teaching career. McIntosh's research career looks at a variety of things, including different parts of mitosis, microtubules, and motor proteins.

References

  1. "Jonathon Howard". Yale.edu.
  2. Novak, Steven J. "Oral history interview with Jonathon Howard". Science History Institute Digital Collections. Retrieved 2023-05-20.
  3. Howard, Jonathon (1982). Kinetics and noise of transduction in insect photoreceptors (Thesis). Australian National University. OCLC   222145173.
  4. 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. PMID   2483095.
  5. 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. doi: 10.1073/pnas.84.9.3064 . PMC   304803 . PMID   3495007.
  6. 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. PMID   2530455.
  7. Sedwick, Caitlin (2014). "Jonathon Howard: Motor proteins go walkabout". Journal of Cell Biology. 204 (2): 150–151. doi:10.1083/jcb.2042pi. PMC   3897180 .
  8. 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. doi:10.1016/S0006-3495(94)80537-5. PMC   1225420 .
  9. 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.
  10. 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. PMID   10559941.
  11. "Former Directors". Max Planck Institute of Molecular Cell Biology and Genetics.
  12. 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. PMID   16672973.
  13. 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.
  14. 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. doi:10.1016/j.cell.2007.11.043. PMC   2311386 .
  15. Riedel-Kruse, I. H.; Hilfinger, A.; Howard, J.; Jülicher, F. (2007). "How molecular motors shape the flagellar beat". HFSP Journal. 1 (3): 192–208. doi:10.2976/1.2773861. PMC   2640991 . PMID   19404446.
  16. 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. doi: 10.1016/j.cub.2004.02.050 .
  17. Riedel, I. H.; Kruse, K.; Howard, J. (2005). "A Self-Organized Vortex Array of Hydrodynamically Entrained Sperm Cells". Science. 309 (5732): 300–303. doi:10.1126/science.1110329. PMID   16002619.
  18. "Jonathon Howard is appointed the Eugene Higgins Professor of Molecular Biophysics and Biochemistry". Yale News. 28 October 2013.
  19. 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. doi:10.1126/science.aad9745. PMC   6535051 . PMID   27230381.
  20. 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. arXiv: 1511.04270 . doi: 10.7554/eLife.13258 .
  21. Rodenfels, J.; Neugebauer, K. M.; Howard, J. (2019). "Heat Oscillations Driven by the Embryonic Cell Cycle Reveal the Energetic Costs of Signaling". Developmental Cell. 48 (5): 646–658. doi:10.1016/j.devcel.2018.12.024. PMC   6414255 .
  22. 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. doi: 10.1073/pnas.2022395118 . PMC   8271565 . PMID   34215693.
  23. 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. doi:10.1126/sciadv.abn0080. PMC   9242452 . PMID   35767611.
  24. Howard, J. (2001). Mechanics of Motor Proteins and the Cytoskeleton. Sinauer Associates. ISBN   978-0878933334.
  25. Mogilner, Alex (2002). "Mechanics of Motor Proteins and the Cytoskeleton". Physics Today. 55 (3): 63–64. doi:10.1063/1.1472396.
  26. Schmitz, Stephan; Veigel, Claudia (2002). "Size matters: Mechanics of Motor Proteins and the Cytoskeleton". J Cell Sci. 115 (14): 2807–2808. doi:10.1242/jcs.115.14.2807.
  27. "Connecticut Academy of Science and Engineering Elects 24 New Members in 2017". Connecticut Academy of Science and Engineering. 15 February 2017.
  28. "Joe Howard honored as 2017 Fellow of the Biophysical Society". Yale.edu. Retrieved 2022-11-08.
  29. "NIH Director's Pioneer Award Program – 2015 Award Recipients". commonfund.nih.gov. 2018-09-18. Retrieved 2022-11-08.
  30. "Find people in the EMBO Communities". people.embo.org. Retrieved 2022-11-08.
  31. "Jonathon Howard". John Simon Guggenheim Memorial Foundation. Retrieved 2022-11-08.
  32. "Sloan Research Fellowship". University of Washington.
  33. Pew Biomedical Scholars. "Jonathon Howard, Ph.D." Pew Biomedical Scholars. Retrieved 2022-11-08.