Dr. Sarah McFarlane, PhD
Professor - Medicine
Cumming School of Medicine, Department of Cell Biology and Anatomy
HBI Education Director
Hotchkiss Brain Institute
Hotchkiss Brain Institute
Child Health & Wellness Researcher
Alberta Children's Hospital Research Institute
BSc. Honours neurophysiology, McGill University, 1987
Doctor of Philosophy Neurophysiology, McGill University, 1992
PDF Developmental Neurobiology, University of California, UCSD, 1993
HBI - Spinal Cord, Nerve Injury and Pain
HBI - Neurodevelopment
Areas of Research
Our research focuses on how developing neurons form connections with each other to generate neural networks. Using the experimentally amenable Xenopus laevis visual system as a model, we investigate factors that regulate the morphological differentiation of a single neuronal type: the retinal ganglion cell (RGC). RGCs receive input on their dendrites from retinal interneurons and pass this information on to the brain via their axons, which make up the optic nerve. At least with the axons, many of the extrinsic factors that direct growth are known. We now need to understand what controls their expression and function. Optic nerve dysfunction, resulting from RGC death, occurs in a number of childhood disorders, including Fetal Alcohol Spectrum Disorder, infantile or congenital glaucoma, or those who suffered from diminished oxygen supply to the optic nerve around birth. In adults, dysfunction can result from glaucoma, multiple sclerosis and metabolic disorders such as Type II diabetes. For RGC replacement therapies to yield their hoped for promise, the new cells will have to be integrated back into the relay circuit controlling vision. Understanding the control of the expression and activity of the key extrinsic factors that regulate these events in the embryo will go some way to giving us the blueprint for re-forming these connections in the adult.
Participation in university strategic initiatives
Retinal degenerative diseases such as glaucoma and diabetic retinopathy exhibit devastating vision loss, each as a result of the death over time of specific types of eye cell. Each disease needs the affected cell types to be replaced, and for the new cells to integrate into functional vision circuits. Thus, we need to explore how different types of eye cell are made and in the right proportions. Importantly, we need to understand these events in the adult eye, because the blueprints likely differ from those for eye cell production in the fetus, from where most of our knowledge comes. The problem is that the mammalian eye is incapable of replacing new eye cells when they degenerate. This is not true in the eyes of adult fish, which retain two subpopulation of cells that allow the eye and retinal circuits to grow throughout life, and that in response to retinal injury are activated and replace lost cells. Importantly, these two classes of cells are also present in the mammalian adult retina, but do not respond to retinal damage by making new cells. The fish eye has the same main classes of eye cells, and with similar functions, as those in humans. Thus, we want to understand how new cells are generated in the fish adult eye, and how these pathways can be harnessed in repair programs after retinal cell loss. We have identified related proteins in the zebrafish eye, Semaphorin3fa and Semaphorin3fb, that our data indicate act on the two key cell populations, both as these cells continue to provide new cells for the ever-expanding eye visual circuits, and as they ramp up their activities in response to eye damage. We are exploring their roles in both contexts with the hope of understanding how to transform the dormant cells of the human adult eye into progenitors like their fish counterparts, so that they too can replace specific eye cell types that get lost in each of the degenerative retinal diseases.
The peripheral nervous system is critical for mounting and coordinating an organism’s response to changes in its internal and external environment. Most cells of the peripheral nervous system -- including pigment cells, neurons and glia -- are derived from neural crest cells (NCC). NCCs are generated at the edge of the forming brain and spinal cord as undifferentiated, proliferative cells that locomote away from the brain to particular target tissues in the periphery, and mature into specific cell types. We understand only some of the steps of this fascinating process. An important knowledge gap is how the organism’s environment influences the production of specific cell types by NCC.
We study the pigmented cells (melanophores) of the skin, because we discovered that environmental light controls the number of melanophores via a specific neural circuit that affects melanophore production by NCC progenitors. This circuit is biologically important, as through the control of pigment cell numbers an organism is afforded camouflage and UV protection. We use a combination of frog and fish embryo models that provide outstanding opportunities to understand how the brain can adjust NCC progenitors and an animal's skin colour: 1) The input to the system (light/dark) can be temporally and spatially controlled, 2) The output of the circuit simply requires counting of skin melanophores, and 3) The entire circuit from eye⇒skin is accessible for experimentation. Defining the cellular and molecular components of the light (environment)⇒NCC (brain)⇒pigment cell (periphery) circuit is the goal of our research program. We are examining how light perceived by the eye acts through a nerve circuit to secrete factors that control NCC biology and thus skin colour.
- Tier II CRC in Developmental Neurobiology, CRC. 2002
- GREATSupervisor Award, Faculty of Graduate Studies, University of Calgary. 2018
- Outstanding Achievement in Supervision Award, University of Calgary. 2004
- AHFMR Scientist, Alberta Heritage Foundation for Medical Research . 2008
- AHFMR Senior Scholar, Alberta Heritage Foundation for Medical Research . 2002
- MRC Scholar, Medical Research Council . 1997
- AHFMR Scholar, Alberta Heritage Foundation for Medical Research . 1997
Administrative Assistant: Suporna Banik (firstname.lastname@example.org)
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