fulton

Chandler Fulton, Ph.D.
Professor of Biology Emeritus

Cell Differentiation and Cell Death

Ph.D., Rockefeller University

contact information
(781) 736-3150

We use techniques of quantitative cell and molecular biology to investigate the orchestration of cell differentiation and cell death. Our research paradigm is a remarkable unicellular eukaryote, Naegleria gruberi, which can alternate between walking amoebae and swimming flagellates. When reproducing amoebae are transferred to a nutrient-free aqueous environment, they undergo synchronous differentiation to streamlined flagellates, a conversion completed within 100 minutes. Amoebae walk using an actin-based motility system, which becomes latent in the flagellates. The flagellates swim using a tubulin-based motility system. The tubulin that makes up the flagellar microtubules is synthesized as a programmed event of differentiation. Thus the cells undergo a yin-yang change in utilization of two fundamental eukaryotic motility systems. Evidence that this differentiation is regulated in part by changes in intracellular free calcium ions led us to calmodulin, the conserved calcium-binding protein that in all eukaryotes transduces the calcium signal to diverse effector proteins. There are two calmodulins in Naegleria flagellates, and they are neatly segregated in the cells, with the major one (CaM-1) localized in the flagella and the other (CaM-2) in the flagellate cell body. During differentiation the mRNAs for the two calmodulins increase in abundance and then rapidly decrease concurrently with those for [[alpha]]-and ß-tubulins. We hope to dissect signal transduction pathways from initiation of differentiation through the regulation of transcription, mRNA stability, and localization of proteins in flagella.

Two major current interests of our lab are derived from this work. The first is the study of a calmodulin-related protein, centrin. Centrin is a centriole-associated calcium-binding protein that somehow participates in a unique type of contractility which receives its energy from binding calcium ions rather than from ATP hydrolysis. This little-understood contractility is involved in movements within all eukaryotic cells, from positioning centrioles for mitosis to the dramatic contraction of the stalks of certain ciliates, such as Vorticella. We are studying the nature of centrin and its associated proteins in an effort to understand the structures it forms and its involvement in motility.

A Naegleria agent induces in vertebrate cells a unique mode of cell death called apoptosis. Apoptosis is crucial in development and throughout life. The Naegleria agent, a small protein, is not toxic to vertebrate cells and does not affect their growth, but causes them to die in a delayed fashion after the cells exit the cell cycle. We wish to define this agent, to understand how it produces delayed apoptosis, and then to explore possible therapeutic uses.

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Selected Publications

Naegleria: A research partner for cell and developmental biology. Fulton, C. (1993). J. Euk. Microbiol. 40:520-532.

A flagellar calmodulin gene of Naegleria, coexpressed during differentiation with flagellar tubulin genes, shares DNA, RNA, and encoded protein sequence elements. Fulton, C., Lai, E.Y. and Remillard. S.P. (1995). J. Biol. Chem. 270:5839-48. [abstract]

A calcineurin-B-encoding gene expressed during differentiation of the amoeboflagellate Naegleria gruberi contains two introns. Remillard SP, Lai EY, Levy YY, Fulton C. (1995).Gene 154: 39-45. [abstract]

Centrin is a conserved protein that forms diverse associations with centrioles and MTOCs in Naegleria and other organisms. Levy, Y.Y., Lai, E.Y., Remillard, S.P., Heintzelman, M.B. and Fulton, C. (1996). Cell Motil. Cytoskel. 33: 298-323. [abstract]

Centrin is synthesized and assembled into basal bodies during Naegleria differentiation. Levy YY, Lai EY, Remillard SP, Fulton C. (1998). Cell Motil Cytoskeleton. 40:249-60. [abstract]

Stable intermediates and holdpoints in the rapid differentiation of Naegleria. Fulton C, Lai EY. (1998) Exp Cell Res. 242:429-38. [abstract]

The genome of Naegleria gruberi illuminates early eukaryotic versatility. Fritz-Laylin LK, Prochnik SE, Ginger ML, Dacks JB, Carpenter ML, Field MC, Kuo A, Paredez A, Chapman J, Pham J, Shu S, Neupane R, Cipriano M, Mancuso J, Tu H, Salamov A, Lindquist E, Shapiro H, Lucas S, Grigoriev IV, Cande WZ, Fulton C, Rokhsar DS, Dawson SC. Cell. 2010 Mar 5;140:631-42. [abstract]

 

Last reviewed:July 1, 2010.

 
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