Fruit fly research helps Ellis unlock biological mysteries

How can the bristles on a fruit fly's back help scientists unlock the mysteries of biological development and even cancer? Scientists like Hilary Ellis, assistant professor of biology, who ask this question and are uncovering some exciting results. Ellis studies the patterning of sensory organs (bristles) on the fruit fly, Drosophila melanogaster. Normally, wildtype flies have a fixed number of bristles that are in constant positions on the fly's back. Just like humans develop ears where ears belong and eyes where eyes belong, fruit flies develop bristles where bristles belong. Ellis seeks to understand the genetic events that control the timing and placement of the sensory bristles during fruit fly development. She hopes that analysis of the genes that regulate fly development will lead to a better understanding of similar events in human development.

All living things that consist of more than one cell, from worms to humans, must solve the fundamental challenge of putting structures in the correct places. This process of patterning during development compares to playing an intricately woven Bach fugue at the piano. The player's fingers must contact the keyboard in the right place, and they need to sound the notes at the appropriate time for the appropriate interval. Each note in the fugue interacts with other notes, each of them also correctly expressed, to produce the final musical form. The notes are like the cells of an organism responding to activated genes and signals from other surrounding cells, eventually producing an organism with all its separate parts in the correct positions. A complex puzzle of genes controls this intricate process of development, and this genetic puzzle fascinates Ellis. Analyzing these kinds of complex genetic interactions is not possible in humans, so Ellis and other scientists have turned to model organisms such as the fruit fly.

Already analysis of the genes involved in establishing the pattern of sensory bristles on flies has proven fruitful. When Leif Ellisen of Stanford University and others sequenced a gene believed to be responsible for a type of human leukemia in 1991, they discovered that the gene they had sequenced was the human version (homologue) of the previously identified fruit fly gene called Notch. Develop-ment of the nervous system and peripheral sensory organs in the fly requires a functional Notch gene. Without Notch too many cells adopt an inappropriate fate and become sensory cells. The disease state of cancer often results from cells adopting inappropriate fates, so the involvement of Notch in fly cell fate decisions is intri-guing. Sci-entists do not know exactly what human Notch does, but studies of the fly gene should help them to understand what may be happening in this particular leukemia.

Ellis' interests center around another fly gene that acts in the process of sensory organ development. The gene is named polychaetoid (pyd). Flies that do not have pyd, like those missing Notch, make too many sensory bristles. This characteristic of the mutant flies suggests that pyd plays an important role in determining cell fates. Understanding what kind of protein pyd encodes and how that protein acts may provide essential clues to understanding fully the critical process of cell fate determination.

Ellis employs a variety of methods to study pyd. One of her aims is to collect new mutations (changes in the DNA or genetic material) that will tell her more about the action of pyd in the fly. She also wants to investigate the interactions between pyd and other genes involved in sensory organ development such as Notch. This research requires countless hours spent at the microscope mating flies and analyzing their offspring for often subtle bristle pattern defects. Although the work can become tedious and labor intensive, Ellis expresses a genuine passion for genetic research.

When she began her undergraduate work at the University of California at Davis, Ellis considered career tracks in both journalism and veterinary medicine. However, her first undergraduate genetics course changed her direction completely. She said of genetics that "it just makes sense -- it's logical." Ellis pursued her passion and developed her abilities in genetic research as a graduate student at MIT in the lab of Robert Horvitz, where she studied the genetic events controlling programmed cell death in the round worm, Caenorhabditis elegans. She began work in developmental biology as a postdoctoral fellow studying frog eye development in William Harris' lab at the University of California in San Diego. Ellis then combined her interest in developmental problems with her passion for genetics in Jim Posakony's lab, also at U.C. San Diego, where she began her present work on fly sensory organ development.

Currently, Ellis serves as a faculty member of the Genetics and Molecular Biology and the Cell and Developmental Biology graduate programs at Emory. She also supports undergraduate research in her lab.

-- Michele Arduengo