Podbilewicz Benjamin , Professor

Phone:  (972)-4-8293454

Building/Auditory:  4-31 Emerson

Research Interests

We are using the nematode Caenorhabditis elegans to investigate cell fusion, organ formation, and nerve cell development. The wealth of anatomical, genetic, developmental, and molecular information available for C. elegans provides a multidisciplinary and powerful approach for these studies. Our work has focused on the study of one fundamental biological question: How do cells fuse? Cells fuse during fertilization and formation of organs. For example, macrophages, eye lens cells, placental cells, and muscle human cells fuse. We also work on how cells migrate, change shapes, and sculpt organs and how cell fusion and organ formation evolve. We initially approached cell fusion by mutational analysis, obtaining many mutations in two genes that we found are critical for the cell fusion process. We identified EFF-1 and AFF-1, two type I membrane proteins essential and sufficient for developmental cell fusion in C. elegans. EFF-1 and AFF-1 are the founders of the first family of eukaryotic cell fusion proteins (fusogens). EFF-1 and AFF-1 from nematodes can fuse heterologous insect cells. EFF-1 is required in both fusing cells and the process is via hemifusion. We will purify and determine the three-dimensional structure of EFF-1 and AFF-1 proteins, we will test their fusogenic activities in cells and in reconstituted liposomes. Our ultimate goal is to understand the molecular and physicochemical mechanisms of cell membrane fusion. We have accomplished a complete description of the cellular events leading to the formation of an organ. Using genetic analyses we identify genes that function to control different cell fusion events in C. elegans and in other organisms and how this process is regulated in development. Homotypic cell-cell fusion may control the size of syncytia by preventing fusion with neighboring cells. We now focus on fertilization, the development of vulva, epidermis, muscles and pharynx.

Pruning of neuronal trees. We discovered that EFF-1 is also required to sculpt complex neuronal trees required for sensing strong mechanical stimuli. We found that EFF-1 trims abnormal or excessive neuronal branches as a novel quality control mechanism. EFF-1 works in specific neurons by fusing excess and abnormal branched neuronal branches. In additional EFF-1 retracts branches. We have identified other genes that participate in the generation and maintenance of complex neuronal trees and we hope that our discoveries in C. elegans may help to understand and repair degenerative diseases of the nervous system and accidental breaking of neurons.

Evolution of organogenesis. We study cellular events during morphogenesis of the vulva across species. We found that changes in the direction of cell divisions can result in differences in size and shape of the vulva. We found that evolution of most vulval characters are biased and proposed that evolution of the vulva in nematodes is governed by selection and/or selection-independent constraints and not by stochastic processes. We are also trying to find missing fusion proteins that act in fertilization and muscle formation in worms and mammals.