There are many different research projects going on in Swindells Hall at the University of Portland. Dr. Ami Ahern-Rindell’s research focuses on genetic disorders and she has been working on a ongoing project on GM1 Gangliosidosis since her graudate education.
GM1 Gangliosidosis is a specific disorder, classified as a lysosomal storage disorder, which affects roughly twenty percent of newborns. Even though Dr. Ahern-Rindell’s research topic seems to affect a very small part of our population, it is very important for newborns with enzyme deficiencies who then have errors in their metabolism. This lysosomal storage disorder is initially caused by a missing enzyme. As lysosomes are the recycling centers of cells, this disorder then causes the cell to lose its ability to break down a metabolism product called GM1Ganglioside which is found in the membranes of neurons as a glycolipid—meaning it has a sugar and lipid portion. When GM1Ganglioside is not broken down its accumulation leads to severe neurological degeneration. Throughout the years, Dr. Ahern-Rindell and her many students have worked to understand what is happening to the gangliosides in this degenerative and severe disease.
For Dr. Ahern-Rindell, the method for understanding the GM1Gangliosidosis started with mice modeling the condition as seen in cats and dogs. It also occurs in cattle, black bears and sheep; the new subject used for her study. Sheep have a different condition from the classic neurological degenerative condition of the cats and dogs, as the GM1gangliosides in sheep are missing the enzyme betagalactasidase, an enzyme responsible for breaking down galactose. GM1ganglioside has a terminal galactose; therefore, without this enzyme the GM1ganglioside accumulates. Another enzyme alphaneuraminidase is also missing in the sheep, but not to the same extent as the betagalactasidase. Through testing in the lab, Dr. Ahern-Rindell found alphaneuraminidase is able to function at about 20% of its normal function when this condition is present in a subject in comparison to 1% for the betagalactasidase. The alphaneuraminidase enzyme removes neuramic acid and acylic acid so the accumulation of these products interferes with the proper removal of GM1ganglioside.
Once this was understood, Dr. Ahern-Rindell wanted to know the genetic mutation in sheep interfering with these enzymes, when the classic condition in dogs and cats did not include the loss of these two enzymes. Dr. Ahern-Rindell found through more investigation that the alphaneuraminidase and betagalactasidase occurred in the lysosome as a complex that joined with a protective protein. It was hypothesized that the interference was found in the DNA where this protective protein is transcribed and that the more deficient betagalactasidase is due to the mutation being near where this gene is found on the DNA strand.
Dr. Ahern-Rindell discovered a mutation in the betagalactasidase genes which changes the structure of this enzyme and can lead to the defective protein complex. Mutations in the complex or alphaneuramidase is being looked into with a cell culture approach. Normal sheep fibroblasts and affected fibroblasts can be analyzed for production rates of fibroblast related to being affected or not. Different DNA sequences can cause mutation while others will not interfere, so it is an elimination process of changing DNA sequences and seeing which ones cause the fibroblast production to decrease. Cluster Regularly Interspaced Short Palindromic Repeats, or CRISPR, is a new technology for gene editing that Dr. Ahern-Rindell is hoping to utilize in her research for this process of elimination as it is simple and effective when manipulating DNA.
One of the challenges of research is funding. Applying for grants may be difficult as a University of Portland professor because of teaching loads, responsibilities within his or her department and fulfilling service requirements. Within the biology department, some funds are dedicated to research and small amounts come from periodic sources like the Butane Faculty Award for summer research and the Murdoc Charitable Trust. These limited resources make the research concentrated so the researcher is effective and accountable. When one is given money to conduct research, the source where the funding came from usually requires the research to be published so that the researcher is held accountable.
Dr. Ahern-Rindell teaches genetics with the lab as a corequisite course—meaning it must be taken with lecture—because she believes the lab is just as important of an environment for the students to learn the subject as the classic classroom. Dr. Ahern-Rindell structures her lab in a way that allows students to take part in the research she is conducting on GM1Gangliosidosis. This is incredibly advantageous to students who are able to contribute in real time during their undergraduate education to research, confirming graduate school plans, and preparing students for independent research or future plans. Dr. Ahern-Rindell has also been able to progress through her research with the thirty or so students she has every semester. Allowing students to help with ongoing research projects is another way to solve the need for funding. She will also have four to eight students engaged in independent research, in which a student works on a designated component of her project to gain skills in research and writing.
Over the 2016 summer session, Dr. Ahern Rindell had research students Raluca Gosman, Kai Seely, Philip Blatt and Michalah Leffler. Raluca shares her experience, stating:
“Research in general is an amazing opportunity to create a relationship with an experienced and smart individual who is an expert in their field, who might also become an influential mentor in your own life. I feel very lucky to have Dr. AR as my research mentor because she guides us through the learning process of doing research while also helping us grow as individuals and as learners. I joined her team originally because the research process is formative in developing a well-rounded understanding of scientific thought. I plan to go to medical school, and while I may not be doing research as part of my career, the critical thinking and reasoning skills I gain from undergraduate research will aid in my success as a doctor.”