Intercellular communication: uncovering mechanisms that coordinate the development of multicellular organisms
- 5123 Rennebohm Hall
- Ph.D., California Institute of Technology, Postdoctoral Research: University of Utah
- Research Interests
- Intercellular communication: uncovering mechanisms that coordinate the development of multicellular organisms
- Research Fields
- Disease Biology, Cell Biology, Developmental Genetics, Drosophila
Development after embryogenesis requires exquisite control of signaling between individual tissues to build an adult organism of the proper shape and size. This intercellular communication is directed by groups of specialized secretory cells that release systemic signals; these signals then orchestrate biological responses in target tissues. Once a tissue has received a signal, it can respond by growing, remodeling, or dying. Thus, the interplay between secretion of systemic signals and response in receiving tissues is essential to unfold the genetically-encoded developmental program of multicellular organisms. One of the most dramatic examples of this interplay between signals and responses occurs during insect metamorphosis, the developmental stage that transforms a crawling larva into a flying adult. In the Bashirullah Lab, we combine forward genetic approaches with cellular and molecular biology to uncover novel essential genes and new biological processes that regulate the onset of and progression through Drosophila metamorphosis. We have discovered important new roles for endocrine and exocrine biology during metamorphosis that have important implications for human development and disease.
Insulin secretion and control of body size: The mechanisms regulating insulin secretion are highly conserved among animals. Just like mammals, insulin plays a critical role in the regulation of metabolism in Drosophila. However, insulin also directly regulates animal body size in flies, akin to insulin-like growth factor (IGF) in mammals. As a result, flies with defective insulin secretion are dramatically smaller than their wild-type counterparts. Using forward genetics, we have identified several novel and conserved regulators of animal body size, many of which may be important for type 2 diabetes in humans. We are now using genetic and cell biology approaches to functionally characterize these newly-identified regulators of insulin secretion.
Developmental control of regulated exocytosis: Regulated exocytosis is a fundamental cell biological process that releases specific cargoes to the extracellular environment in a stimulus-dependent manner. Importantly, dysregulation of this process underlies many human diseases, including endocrine disorders like diabetes and exocrine disorders like asthma and respiratory distress syndrome. Our experimental model system is the Drosophila larval salivary gland, which utilizes regulated exocytosis to secrete mucin-like “glue” proteins at the onset of metamorphosis. Salivary glands are composed of large cells that produce glue-containing secretory granules which are several micrometers in diameter, providing an ideal in vivo context to identify and characterize new proteins that play a role in regulated exocytosis. We have identified new and unexpected regulators of intracellular trafficking, and we are focused on understanding how these proteins impact the regulated exocytosis pathway.
Genetic and hormonal control of metamorphosis: The process of transforming a juvenile larva into a mature adult fly is remarkably complex; nearly every tissue present in the larval organism is dismantled and rebuilt or remodeled. However, the mechanisms that regulate this rebuilding of the organism remain unknown, providing an ideal opportunity to uncover new biological processes. One of the critical regulators of metamorphosis is the steroid hormone ecdysone. Systemic pulses of ecdysone direct developmental progression and trigger tissue remodeling during metamorphosis. Our lab has a large, unique collection of metamorphosis-specific lethal mutations derived from a forward genetic screen. We are using these mutations to genetically dissect ecdysone signaling as well as the biological processes that ecdysone coordinates during metamorphosis.
Search PubMed for more publications by Arash Bashirullah
Neuman, S.D. Bashirullah, A. (2018). Hobbit regulates intracellular trafficking to drive insulin-dependent growth during Drosophila development. Development. 145: dev161356.
Pallilyil, S., Zhu, J., Baker, L.R., Neuman, S.D., Bashirullah, A., Kumar, J.P. (2018). Allocation of distinct organ fates from a precursor field requires a shift in expression and function of gene regulatory networks. PLoS Genetics. 14(1): e1007185
Kang Y, Neuman SD and Bashirullah A (2017). Tango7 regulates cortical activity of caspases during reaper-triggered changes in tissue elasticity. Nature Communications, 8(1):603.
Kang Y, Marischuk K, Castelvecchi GD, Bashirullah A (2017). HDAC Inhibitors disrupt programmed resistance to apoptosis during Drosophila development. G3, 7(6): 1985-1993.
Weasner BM, Weasner BP, Neuman SD, Bashirullah A, Kumar JP (2016). Retinal expression of the Drosophila eyes absent gene is controlled by several cooperatively acting cis-regulatory elements. PLoS Genetics, 12(12):e1006462.
Kang, Y. and A. Bashirullah (2014). A steroid-controlled global switch in sensitivity to apoptosis during Drosophila development. Developmental Biology, 386(1): 34-41.