Dartmouth professor Elizabeth Smith. Image acquired from https://sites.dartmouth.edu/efsmithlab/
Leading researchers involved in the study of cilia and flagella presented their work at the Vermont Academy in July 2010 as part of a conference sponsored by the Federation of American Societies for Experimental Biology. Professor Elizabeth Smith of the Dartmouth Biology Department attended the meeting and wrote a report on the proceedings, which has been published in a recent issue of Science Signaling (1).
Cilia and flagella are derivatives of the cytoskeleton in eukaryotes, comprised of a distinctive ring of nine microtubule doublets. Interestingly, while bacteria also possess flagella, bacterial flagella are believed to have developed independently of the eukaryotic structures from secretory pathways. Furthermore, bacterial flagella rotate to produce motion, in contrast with the beating motion of eukaryotic cilia and flagella. The beating is produced by dynein motor proteins, located at junctions between microtubules in the rings, which cause microtubules to slide relative to one another. The coordinated sliding of microtubules drives bending of the entire structure, producing a remarkable biological motor whose processes remain a focus of study in cell biology.
As Smith notes in her article, the study of cilia and flagella has long been associated with observational science. The careful study of electron micrographs by Sergei Sorokin in 1962, for example, led to the first theories of ciliogenesis. Today, researchers like Michel Leuroux, a presenter from Simon Fraser University, use proteomic information to study how centrioles develop into basal bodies, reach the cell membrane and produce a ring-shaped axoneme, at the correct point in the cell cycle and in an optimal arrangement. Leuroux focuses on the proteins present in the transition zones separating basal bodies from the axoneme that, when present in mutant forms, give rise to a host of human diseases associated with defects in cilia. Using the nematode Caenorhabditis elegans as a model, Leurox determined that transition zone ciliopathy proteins immobilize basal bodies when they reach the membrane and establish the transition zone, critical points of failure in ciliogenesis.
Other subfields of current cilia research discussed at the conference included intraciliary transport, responsible for the movement of additional protein building blocks to the expanding tip of a maturing cilium, cellular signaling in non-motile primary cilia and the structure of the axoneme.
According to the website of the Elizabeth Smith Lab, Professor Smith’s research at Dartmouth deals primarily with the control of dynein activity in cilia, which directly affects the pattern of beats produced by the organelles. The lab is pursuing an observed relationship between calcium concentration, detected by complexes of calmodulin, and flagellar motility. These complexes are distributed differentially across the axoneme, with a particularly high affinity observed for the C1 microtubule of the central apparatus (2). Studies probing the composition of the protein complexes that bind calmodulin in the green alga Chlamydomonas revealed the presence of a homologue of the mammalian protein Pcdp1 (3). Furthermore, reduction in expression of calmodulin-binding complex constituents resulted in malformation of the axoneme and defects in motility, demonstrating the essential role of the complex, a component of the central apparatus, in the proper functioning of cilia (3).
Professor Smith’s debriefing of the past year’s cilia conference will help to inform researchers on the current direction of cilia research. Her own research looks to continue to be a fruitful source of insight for both the Dartmouth Biology Department and the cilia research community at large. In 2009, Smith was named a K.R. Porter Fellow, which assists in her efforts to encourage the development of young research scientists. Smith will be teaching Biology 71, “Current Topics in Cell Biology,” in the 2011 spring term.
References:
- E. F. Smith, R. Rohatgi,Science Signaling, 4(155), mr1, (2011).