There are a myriad of fascinating research projects going on in University of Portland’s Swindells Hall, including Dr. Amelia Ahern-Rindell’s genetics research. Since graduate school, Dr. Ahern-Rindell has focused her research on the cellular and molecular characterization of a specific fatal genetic disorder, GM1 gangliosidosis (GM1).
GM1 belongs to a class of diseases called lysosomal storage disorders (LSDs). The lysosome is the “recycling center” of the cell; it degrades various waste macromolecules and recycles their building blocks for reuse. In LSDs, a specific lysosomal enzyme is nonfunctional or deficient. As a result, waste molecules can accumulate within the lysosome and kill the cell.
In GM1, the deficient enzyme activity is beta-D-galactosidase, which normally cleaves galactose sugar molecules from glycoproteins, glycolipids, and oligosaccharides. GM1 results in the accumulation of these galactose-containing molecules within the lysosome and eventually leads to the death of the cell. The effects of GM1 are especially profound within nerve cells, which contain high concentrations of GM1 ganglioside, which is a glycoprotein containing galactose. Therefore, GM1 usually presents as a neurological disorder. Unfortunately, there is no known cure for GM1 or many of the other LSDs. Much of the current research into GM1 is performed using animal models of the disorder, and Dr. Ahern-Rindell’s work is no exception.
Dr. Ahern-Rindell has researched several animal models of GM1, including the cat and dog models, but her doctoral work focused on an ovine model. Biochemical and genetic characterization of this model revealed that it is unique: in addition to the primary deficiency in beta-gal, the ovine model also exhibited a less severe secondary deficiency in the enzyme activity of alpha-neuraminidase (alpha-neur). This dual deficiency is not seen in other models of GM1. Throughout her graduate education and post-doctoral experience, Dr. Ahern-Rindell has used several techniques, including recombinant DNA techniques and the polymerase chain reaction (PCR), that she would later teach to her students at the University of Portland.
At the University of Portland, Dr. Ahern-Rindell’s attention remained on her unique ovine model of GM1. For over twenty years, she has worked to characterize this model and sequence the gene that codes for beta-gal in order to identify the mutation that causes the observed dual enzyme activity deficiency. Her work is, in part, based on the fact that beta-gal complexes with alpha-neur and a third molecule called the “protective protein” within the lysosome. Dr. Ahern-Rindell’s guiding hypothesis is that a mutation in the beta-gal gene alters the protein’s structure and interferes in its ability to complex with alpha-neur and the protective protein. This destabilizes both beta-gal and alpha-neur within the lysosome, resulting in their premature degradation and explaining the observed dual enzyme activity deficiencies. Dr. Ahern-Rindell and her UP students have been presenting their findings at numerous conferences over the years. She plans to submit a summative manuscript co-authored with many of her students soon in the hopes that their findings could help develop a treatment for GM1 and related LSDs.
Throughout her time at the University of Portland, Dr. Ahern-Rindell has involved undergraduates in her work. In addition to mentoring several students in her undergraduate research group, she also brings her research directly into her Genetics Lab course. In this unique course, students are able to answer original questions about Dr. Ahern-Rindell’s unique ovine model of GM1. This not only allows the students to contribute in a meaningful way to Dr. Ahern-Rindell’s research, but also gives them the opportunity to participate in authentic science. According to Dr. Ahern-Rindell, this “helps students learn techniques and become comfortable doing group work as they engage in the process of doing science.” Dr. Ahern-Rindell challenges her research group and her Genetics Lab course students to carry out protocols and think through problems on their own, which Dr. Ahern-Rindell says “fosters independence and helps them figure out what their strengths and weaknesses are. It also help them be ready for the next step in their careers once they leave UP.” Her research students agree; Raluca Gosman thinks that Dr. Ahern-Rindell’s approach “helps you gain confidence being independent and fosters a clear understanding of why you are doing things.”
Dr. Ahern-Rindell has also championed undergraduate research at the university level and beyond. She is the faculty advisory for the UP Undergraduate Research Club, serves on the UP Undergraduate Research Advisory Board, was elected as the president of the national organization known as CUR, the Council on Undergraduate Research, and written several scholarly articles about integrating original research into the undergraduate teaching laboratory. Through her work on GM1 and her commitment to undergraduate research, Dr. Ahern-Rindell has truly enriched the University of Portland and the lives of her countless students.