B.A. (Biochemistry), 1987, Cornell University, Ithaca, NY
Ph.D. (Neuroscience), 1993, Yale University, New Haven, CT
Postdoctoral Fellow, University of California-San Diego, CA
Postdoctoral Fellow, University of Virginia, Charlottesville, VA
My laboratory focuses on two different aspects of the biology of the fruit fly Drosophila melanogaster. With both projects, are goal is combine multiple experimental approaches--genetic, molecular, and physiological/behavioral--to understand as fully as possible the processes that we are studying. Descriptions of the two projects are given below.
We are studying the adult lethal gene drop-dead (drd) which, when mutated, causes flies to die during the first week of adult life. The drd gene encodes a so-called NRF domain protein—a member of a family of integral membrane proteins with some homology to bacterial acyl transferases. No biochemical function has yet been determined for any eukaryotic NRF domain protein. While drd has previously been reported to cause neurodegeneration, we have found that the mutant flies also have many other phenotypes. First, they have a problem moving food through their guts, as they end up with a large amount of food stuck in the crop, which is a food storage organ (see figure below). Second, mutant female flies are sterile, due to a defect in the cross-linking of some of the proteins that make up the eggshell.
In our lab, we make use of a variety of different genetic and biochemical techniques to understand the function of drop-dead. Recently, we have found that drd expression is required during metamorphosis, but not during adulthood, for adult viability. Also, we find that expression in multiple tissues is required for survival, suggesting that there might be multiple “causes of death” when the drd mutant flies die. Ongoing projects in the lab include screening for genes that lie in the same metabolic pathway as drd, identifying the drd expression pattern, and studying the defect in eggshell formation in drd mutant females.
Distribution of food within the gut of wild-type and mutant flies. On the left is the dissected gut of a wild-type fly that was kept on blue food. Note that food is present in the midgut (Mid) and rectum (Rec) but not in the crop (Cr) or cardia (Car). In contrast, the gut from a drd mutant fly (right) has a large amount of food in the crop and some staining also in the cardia.
Many of the important homeostatic processes that are necessary for life, such as regulation of water and ionic balance or the absorption of nutrients, are mediated by transport across epithelial cell layers. Precise control of such transport pathways is essential for an organism to adapt to a changing environment. In this project we are studying a model transport epithelium, the Malpighian tubules, which function as the fly’s kidney. The Malpighian tubules produce urine by transporting ions—primarily potassium and chloride—and water out of the hemolymph and into the tubule lumen, which is contiguous with the gut. The rate of urine secretion is controlled by many diuretic and antidiuretic factors in response to changes in the hydration and feeding state of the fly. We have discovered that the biogenic amine tyramine (which is the compound found is red wine and cheese that some have linked to migraines) acts as one of these diuretic factors (Blumenthal, 2003). Application of tyramine causes an increase in the conductance of chloride across the tubule and thus an increase in urine production. We also find that not only can the tubule respond to tyramine, it can also synthesize it from the amino acid tyrosine. As shown in the figure below, we have found that tyramine synthesis and reception occur in different cells in the tubule. Tyramine is synthesized in the principal cells from tyrosine by the enzyme tyrosine decarboxylase, encoded by the gene Tdc1. The tyramine then activates receptors on the stellate cells—primarily the receptor encoded by the gene tarot (tro, for TA Receptor Of the Tubule, aka CG7431). This is the first example of cell-cell communication in an insect Malpighian tubule. Current projects ongoing in the lab involve characterizing second messenger pathways that modulate the response of the tubule to tyramine and identifying other gene products necessary for the synthesis and release of tyramine.
Model of tyramine (TA) action in the Malpighian tubule. In our model, tyrosine is taken up into the principal cells of the tubule (white) and converted into tyramine by the enzyme tyrosine decarboxylase (TDC). The tyramine is released from the principal cells and binds to receptors on the stellate cells (green), stimulating an increase in chloride conductance and urine secretion.
Blumenthal, E.M., and Sansone, C.L. 2012. Developmental expression of drop-dead is required for early adult survival and normal body mass in Drosophila melanogaster. Insect Biochem. Mol. Biol. 42(9): 690-698.
Blumenthal, E.M. 2009. Isoform- and cell-specific function of tyrosine decarboxylase in the Drosophila Malpighian tubule. Journal of Experimental Biology 212:3802-3809. doi:10.1242/jeb.035782.
Peller, C.R., Bacon, E.M., Bucheger, J.M., and Blumenthal, E.M. 2009. Defective gut function in drop-dead mutant Drosophila. Journal of Insect Physiology 55:834-839. First published online 7/19/2009; 10.1016/j.jinsphys.2009.05.011
Blumenthal, E.M. 2008. Cloning of the neurodegeneration gene drop-dead and characterization of additional phenotypes of its mutation. Fly 2:4, 1-9. Published online: http://www.landesbioscience.com/journals/fly/article/6546
Blumenthal, E. M. 2005. Modulation of tyramine signaling by osmolality in an insect secretory epithelium. Am. J. Physiol. Cell Physiol. 289, C1261-C1267. First published 6/29/2005; 10.1152/ajpcell.00026.2005 http://ajpcell.physiology.org/cgi/content/full/289/5/C1261
Blumenthal, E. M. 2003. Regulation of chloride permeability by endogenously produced tyramine in the Drosophila Malpighian tubule. Am. J. Physiol Cell Physiol. 284, C718-C728. First published 11/20/2002; 10.1152/ajpcell.00359.2002 http://ajpcell.physiology.org/cgi/content/full/284/3/C718
Blumenthal, E. M. 2001. Characterization of transepithelial potential oscillations in the Drosophila Malpighian tubule. J. Exp. Biol. 204, 3075-3084. http://jeb.biologists.org/cgi/content/full/204/17/3075
Tayler Sheahan, Laura Korthauer, and Edward Blumenthal. Female sterility and compromised eggshell integrity of drop-dead mutants. Presented at the Drosophila Research Conference, San Diego, CA, March 30-April 3, 2011.
Christine Sansone and Edward Blumenthal. Temporal and spatial requirements for drop-dead expression. Presented at the Drosophila Research Conference, San Diego, CA, March 30-April 3, 2011.
Edward M. Blumenthal. Regulation of epithelial ion transport by tyramine: Cell-to-cell communication in the Drosophila Malpighian tubule. Presented at the Society for Experimental Biology Annual Meeting, Glasgow, Scotland, July 1-4, 2011.
Chrissy Sansone (Ph.D. student)
Dr. Blumenthal is currently accepting new Ph.D. students into his lab
Julie Bucheger, 2004, B.S.
Joe LaPlaca, 2004, B.S.
Jen Krueger, 2005, B.S.
Graham Smith, 2005, B.S.
Tiffani Cherry, 2006, B.S.
Amanda Herman, 2006, B.S.
Matt Klinker, 2004, B.S.
Will Mueller, 2007, B.S.
Cassie Peller Nelson, 2008, B.S.
Nic Haas, 2008, B.S.
Elizabeth Bacon (Summer Research Program, 2007)
Laura Korthauer, 2009, B.S.
Jackie Whelan, 2009, B.S.
Olivia Corradin, 2010, B.S.
Jennifer Rorex, 2010, B.S.
Kristen Ruka, 2010, B.S.
Kendall Knight (Summer Research Program, 2010)
Francisco Nava, 2011, B.S.
Megan Mohnen (2013, B.S.)
Anna Quint (2012 B.S.)
Katie Schober (2012 B.S.)
Tayler Sheahan (2012 B.S.)
Sam Schultz (undergraduate technician)
Catharine Skoog (undergraduate researcher)
Dr. Haiying Zhang (postdoctoral fellow)