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EDWARD M. BLUMENTHAL
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Epithelial Physiology and Control of Feeding/Digestive Behavior
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.
Project 1: The adult lethal gene drop-dead and control of food processing What controls hunger and appetite? What are the signaling pathways that monitor nutritional state and link it to feeding? Answering these questions is of obvious importance to human health. In our lab, we are using Drosophila to study genes involved in feeding behavior and digestion. We are studying the adult lethal gene drop-dead (drd) which, when mutated, causes flies to die during the first week of adult life. While drd has previously been reported to cause neurodegeneration, we have found that the mutant flies also 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). Current projects in the lab include determining the expression pattern of the drd gene, characterizing more fully the phenotype of mutant flies, and screening for other genes that interact with drd.
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.
Project 2: Control of epithelial ion and water transport 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 believe that tyramine synthesis and reception occur in different cells in the tubule, making tyramine an agent for cell-cell communication. Current projects ongoing in the lab involve identifying the specific gene products that act as the tyramine receptor, as the decarboxylase enzyme that converts tyrosine to tyramine, and as the transporter that imports tyrosine into the principal cells of the tubule.
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.
Selected Publications 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 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. 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. 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
Abstracts Presented During 2007-08 Cassandra R. Peller and Edward M. Blumenthal. Alterations in triglyceride levels and feeding behavior by a mutation in lot’s wife. Presented at the Drosophila Research Conference, San Diego, CA, April 2-6, 2008. Elizabeth M. Bacon and Edward M. Blumenthal. Effect of starvation and mutation of lot’s wife on crop motility in Drosophila. Presented at the Drosophila Research Conference, San Diego, CA, April 2-6, 2008. Edward M. Blumenthal. Molecular dissection of tyraminergic communication in the Drosophila Malpighian tubule. Presented at Experimental Biology, San Diego, CA, April 5-9, 2008. Edward M. Blumenthal. Molecular dissection of tyraminergic communication in the Drosophila Malpighian tubule. Presented at the Society for Experimental Biology annual meeting, Marseille, France, July 6-10, 2008.
Current Lab Personnel Julie Bucheger (MU 2004), Research Technician Laura Korthauer (undergraduate researcher) Jackie Whelan (undergraduate researcher) Olivia Corradin (undergraduate researcher) Jennifer Rorex (undergraduate researcher)
Past Lab Personnel Joe LaPlaca (MU 2004) Jen Krueger (MU 2005) Graham Smith (MU 2005) Tiffani Cherry (MU 2006) Amanda Herman (MU 2006) Matt Klinker (MU 2004) Will Mueller (MU 2007) Cassie Peller (MU 2008) Elizabeth Bacon (Summer Research Program 2007) |
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Box 1881 · Milwaukee, Wis. USA · 53201-1881
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