About Dr. Dubreuil's Research
The lab has a long-standing interest in how scaffold proteins like spectrin and ankyrin help to manage the complexity of the plasma membrane in animal cells. Plasma membrane function relies on thousands of proteins that carry out transport, adhesion, signaling, traffic, and more. Our research is aimed at understanding how the cell keeps track of all of these players to modulate their activity and make sure that the needs of the cell are always met. We are using the fruit fly Drosophila as a simple model system where genetic tools can be used to address basic questions of protein function. The similarities between spectrins and ankyrins in Drosophila and humans are striking, suggesting that they have similar cellular effects across species.
The genetic approach has yielded many surprising new insights into spectrin biology. Recently we have become interested in the effects of spectrin on dietary fat uptake and storage in Drosophila larvae. Some spectrin defects block formation of lipid droplets in fat tissue, others cause abnormal accumulation of fat in the cells of the digestive tract. The fat processing machinery relies on lipoprotein carriers that are related to human LDL and VLDL. Genetic studies in Drosophila are uncovering novel mechanisms for loading and unloading these lipoproteins as they move fat from tissue to tissue and for packaging fat into lipid droplets for storage. Further studies of these mechanisms will broaden our understanding of fat trafficking in animal systems and may well shed light on the current obesity epidemic in humans.
Our interest in the biology of the gut epithelium in Drosophila has led us to another important area of research. As in many other invertebrates, the digestive tract of Drosophila larvae is lined with a specialized extracellular matrix (known as the Peritrophic Membrane or PM). The PM is like a sausage casing that is continually secreted at the anterior end of the gut and moves like a conveyor carrying food and ultimately waste through the organism. It is impervious to almost everything we can feed to larvae, supporting its suggested function as a barrier against infection and mechanical damage to the epithelial cells that form the digestive tract. Secretion of the PM is intriguing from the standpoint of epithelial biology and also digestive physiology. Somehow nutrients and digestive enzymes must efficiently pass through this formidable barrier. The development of ways to breach the PM barrier is likely to have useful implications for the development of new insecticides and will also improve our understanding of disease agents causing malaria and sleeping sickness, which have already figured out a way to get through
G. H. Mazock, A. Das, C. Base, and R. R. Dubreuil (2010) Transgene rescue identifies an essential function for Drosophila beta spectrin in the nervous system and a selective requirement for ankyrin-2-binding activity. Mol. Biol. Cell
R. R. Dubreuil, A. Das, C. Base, and G. H. Mazock (2010) The Drosophila Anion Exchanger (DAE) lacks a detectable interaction with the spectrin cytoskeleton. J. Negat. Results Biomed
A. Das and R. R. Dubreuil (2009) Spectrin: Organization and function in neurons. In Encyclopedia of Neuroscience (LR Squire et al, eds), Elsevier Ltd, pp. 213-218.
A. Das, C. Base, D. Manna,W. Cho, R.R.Dubreuil (2008) Unexpected complexity in the mechanisms that target assembly of the spectrin cytoskeleton. J. Biol. Chem.
D.S. Garbe, A. Das, R.R. Dubreuil, G.J. Bashaw (2007) Alpha and beta spectrin function independently of ankyrin to regulate the establishment and maintenance of axon connections in the Drosophila
embryonic CNS. Development
R. R. Dubreuil (2006) Functional links between membrane transport and the spectrin cytoskeleton. J. Membrane Biology.
A. Das, C. Base, S. Dhulipala, R.R. Dubreuil (2006) Spectrin functions upsteam of ankyrin in a spectrin cytoskeleton assembly pathway. J. Cell Biol.