Researchers in the making:
Scientific exploration
Dr. Alicia Ebert’s scientific career is just getting started, but she has already made two important discoveries about the role of proteins in embryonic development.
Story by Julie Sedivy/Photos by Trudie Lee
Embarking on a scientific journey is similar to a long, open-ended backpacking trip: scientists rarely know where the trails of hypotheses and evidence will lead them. Sometimes, they soldier on without much to show for their efforts; other times, they make small steps in scientific understanding; and occasionally, they come across new, uncharted landscape that needs to be explored. Dr. Alicia Ebert, a postdoctoral fellow in the lab of Dr. Sarah McFarlane at the University of Calgary, is one such scientific explorer who is charting new territory in the area of proteins and embryonic development.
When the eye begins to form in an embryo, cells that will make up the eye begin to specialize into different cell types. Retinal ganglion cells, which send signals from the retina to the brain along axons, are among the first cells to become specialized. Axons are long fibres in nerve cells that are responsible for carrying outgoing messages to other cells. As these retinal cells form, the axons must find a way to connect to the right cells in the developing brain. Along the way, the axons are guided by proteins that act like stoplights indicating the correct path that axons need to follow. Much of the work in Dr. McFarlane’s lab is devoted to understanding how this process works.
When Dr. Ebert arrived in Dr. McFarlane’s lab, she began using zebrafish to investigate the effects of various proteins on axon guidance. Zebrafish are ideal for studying early eye development because their eyes develop outside their bodies. Her studies turned up little in the way of definitive results until she genetically manipulated zebrafish in a way that reduced their ability to produce a particular class of proteins called plexins. Her research with plexins then led to an unexpected discovery.
Dr. Ebert expected to see abnormalities in the routing of axons to the brain, but instead, she discovered that the plexin-deficient zebrafish either developed no eyes at all or developed abnormally small eyes. In other words, a protein that was suspected to play a role in axon guidance turned out to also affect early eye formation. These eye abnormalities also manifest in humans, resulting in rare congenital defects known as anopthalmia (which translates from the Greek as “without eye”) and micropthalmia (“small eye”), which occur roughly once or twice every 10,000 births.
Novel findings like these can be extremely exciting, but as Dr. Ebert points out, it’s not enough simply to have results. She feels it’s also essential to be able to offer a plausible explanation of the result—and the more unexpected the result, the more important it is to address the question of why and how it occurred. Her current research is aimed at learning more about how plexins affect early eye development. This requires her to delve into new terrain in search of the underlying causes and to design additional experiments to test her emerging hypotheses.
Coming across a novel discovery like this is unusually good luck for any young researcher. But this is the second time in her research career that Dr. Ebert has stumbled across an unknown function of a known protein—a coincidence that she likens to being struck by lightning twice. The first time occurred when she was investigating the role of a particular protein in regulating the entry of calcium into the cells of a developing heart. Much to her surprise, the protein also turned out to affect how cells migrate to their proper location in the very early stages of embryonic development. Dr. Ebert also found that reducing these proteins led to the death of zebrafish embryos shortly after fertilization.
Dr. Ebert harbours no illusions that her scientific life will always be this eventful. But her early discoveries have no doubt increased her interest in scientific exploration.