SEM of Chlamydomonas reinhardtii

David Howard's Research Page

 Corbicula fluminea sperm

I am currently looking for Masters of Science students and undergraduate researchers. Stipend funding is likely for the right students.  Click here to find out more about these research opportunities in the Howard lab.

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Example Publications Chlamydomonas Research Normal Life

Overview of Research Interests

Research in my lab investigates how organisms generate and control movement at the cellular and molecular levels.  This area of biology is called cell motility and the cytoskeleton.  Most of my work is focused on understanding what controls the speed and strength of beating in cilia and flagella.  Cilia and flagella are long, thin organelles that extend from eukaryotic cells.  Cilia and flagella beat by propagating bends down their length.  This beating is cartooned in the animation below.

Cartoon of Chlamydomonas swimming The single-celled green alga Chlamydomonas reinhardtii has two flagella which beat to cause the cell to swim through liquid.  The Chlamydomonas in the cartoon would be swimming toward the top of the screen.  The beating has been slowed down about 50X so that you can see a full beat cycle.  Ordinarily, the flagella beat too fast for the eye to see. 

(Visit the Chlamy Center)

Widespread Importance of Cilia & Flagella

Virtually all animals, many protists, and all lower plants (mosses and ferns) possess cilia &/or flagella and use them for one or more vital functions.  Common examples of cilia and flagella include the sperm tails of swimming sperm, the respiratory cilia which clean out the respiratory tract in mammals, and oviductal cilia which help move the egg down the Fallopian tubes in mammals.  (Visit the Talbot Lab to see movies of this in action.)

Cilia and Flagella in Human Health

Numerous human diseases are caused by defective cilia and/or flagella.  Some of these diseases include:

  • Developmental defects that cause internal organs to be misplaced or malformed (primary ciliary dyskinesia 1/20,000 births1, Kartagener syndrome1, and lateralization defects 1/8,000 births3)
  • A disease that results in numerous cysts developing in the kidneys which damage the kidneys (polycystic kidney disease at 1/10,000 births)4,11
  • Degeneration of the retina and loss of sight in diseases like retinitis pigmentosa10,12
  • Bardet-Biedl syndrome, a relatively rare disorder associated with a variety of health problems including retinal degeneration, obesity, kidney malformations, polydactyly, and learning disabilities.2,9
  • Defects in brain development (hydrocephalus)8
  • Male infertility due to immotile or poorly motile sperm1,7
  • Reduced female fertility due to immotile oviductal cilia1

In addition to these diseases, recent evidence indicates that primary cilia are the strain sensors in bone cells called osteocytes14.  Thus, cilia may also be important in controlling bone density and osteoporosis.

Current and Recent Research Focus

Numerous lines of evidence indicate that the enzyme cAMP-dependent protein kinase (PKA) is involved in the regulation of flagellar beating.  As a kinase, this PKA enzyme should exert its effects by phosphorylating one or more proteins to turn these proteins on or off.  However, the targets of PKA are not known for most cilia and flagella, including those of humans.  Although we are interested in all aspects of flagellar beating, most recent efforts in my lab have been focused on studying flagellar PKA.  

For most of our work, we use the model organism Chlamydomonas to study flagellar PKA and the control of flagellar beating5.  Chlamydomonas is the most powerful model system for studying cilia and flagella, and much of the recent progress in understanding human diseases related to cilia and flagella comes from studying this organism3,7,13. 

Go to our Chlamydomonas research page to find out what's going on now.

SEM of Chlamydomonas

Chlamydomonas

 

Corbicula sperm with 2 flagella

Corbicula sperm

 In sperm flagella, PKA often acts to initially activate beating of the flagella and thus swimming of the sperm.  Colleen Trantow6 (an undergraduate in my lab) recently investigated PKA in the sperm from the Asian clam Corbicula fluminea.  Corbicula sperm are highly unusual because they possess two flagella (indicated by the A and B in the figure to the left) instead of one.  We found that PKA activates both flagella in Corbicula.  Furthermore, Colleen found that the related enzyme PKG also activates motility.  This was the first clear case of both PKA and PKG activating sperm motility6.

Literature Cited

  1. Afzelius BA, Mossberg B, & Bergstrom SE. 2001. Immotile cilia syndrome (primary ciliary dyskinesia), including Kartagener syndrome.  in The Metabolic and Molecular Bases of Inherited Disease, eds. Scriver, C. R., Beaudet, A. L., Sly, W. S. & Valle, D. (McGraw–Hill, New York), pp. 4817–27.

  2. Ansley SJ, Badano JL, Blacque OE, Hill J, Hoskins BE, Leitch CC, Kim JC, Ross AJ, Eichers ER, Teslovich TM, Mah AK, Johnsen RC, Cavender JC, Lewis RA, Leroux MR, Beales PL, Katsanis N.  2003. Basal body dysfunction is a likely cause of pleiotropic Bardet-Biedl syndrome. Nature. 425:628-33.

  3. El Zein L, Omran H, Bouvagnet P. 2003. Lateralization defects and ciliary dyskinesia: lessons from algae. Trends Genet. 19:162-7.

  4. Hirokawa N, Takemura R. 2003. Biochemical and molecular characterization of diseases linked to motor proteins. Trends Biochem Sci. 28:558-65.

  5. Howard DR, Habermacher G, Glass DB, Smith EF, Sale WS.  1994. Regulation of Chlamydomonas flagellar dynein by an axonemal protein kinase. J Cell Biol 127:1683-92.

  6. Howard, D.R., C.M. Trantow, and C.D. Thaler. 2004. Motility of a biflagellate sperm: Waveform analysis and cyclic nucleotide activation.  Cell Motil. Cytoskel.  59:120-130.

  7. Ibanez-Tallon I, Heintz N, Omran H.  2003. To beat or not to beat: roles of cilia in development and disease. Hum Mol Genet. 12 Spec No 1:R27-35.

  8. Ibanez-Tallon I, Pagenstecher A, Fliegauf M, Olbrich H, Kispert A, Ketelsen UP, North A, Heintz N, Omran H. 2004.  Dysfunction of axonemal dynein heavy chain Mdnah5 inhibits ependymal flow and reveals a novel mechanism for hydrocephalus formation.  Hum Mol Genet. 13:2133-41.

  9. Li JB, Gerdes JM, Haycraft CJ, Fan Y, Teslovich TM, May-Simera H, Li H, Blacque OE, Li L, Leitch CC, Lewis RA, Green JS, Parfrey PS, Leroux MR, Davidson WS, Beales PL, Guay-Woodford LM, Yoder BK, Stormo GD, Katsanis N, Dutcher SK.  2004. Comparative genomics identifies a flagellar and basal body proteome that includes the BBS5 human disease gene. Cell. 117:541-52.

  10. Marszalek JR, Liu X, Roberts EA, Chui D, Marth JD, Williams DS, Goldstein LS. 2000.Genetic evidence for selective transport of opsin and arrestin by kinesin-II in mammalian photoreceptors. Cell. 102:175-87.

  11. Pazour GJ, Dickert BL, Vucica Y, Seeley ES, Rosenbaum JL, Witman GB, Cole DG.   2000. Chlamydomonas IFT88 and its mouse homologue, polycystic kidney disease gene tg737, are required for assembly of cilia and flagella. J Cell Biol.151:709-18.

  12. Pazour GJ, Baker SA, Deane JA, Cole DG, Dickert BL, Rosenbaum JL, Witman GB, Besharse JC.  2002. The intraflagellar transport protein, IFT88, is essential for vertebrate photoreceptor assembly and maintenance. J Cell Biol. 157:103-13.

  13. Snell WJ, Pan J, Wang Q.  2004. Cilia and flagella revealed: from flagellar assembly in Chlamydomonas to human obesity disorders. Cell.  117:693-7.

  14. Whitfield JF.  2003. Primary cilium--is it an osteocyte's strain-sensing flowmeter?  J Cell Biochem. 89:233-7. 

 This is not an exhaustive list of the literature in this area, but merely a place for the interested to start learning.

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Last Modified:  July 2005