Yeast and zebrafish are among the lab organisms being recruited to the search for rare disease cures.
Rare diseases are not so rare. About 300 million people worldwide live with the more than 7000 individual diseases that are designated “rare” by the US government. But because each of these affect so few individuals, the usual resources and research that lead to new treatments are not available. That’s why scientists have had to get creative.
Studying organisms that may at first glance seem totally unrelated to humans is proving an important tool for understanding and finding treatments for rare disease. In a review in GENETICS, Strynatka et al. outline the ways in which laboratory model organisms are paving the way for life saving therapies, with a particular emphasis on baker’s yeast and zebrafish. Check out the review to learn more about the ingenious methods being applied, but in honor of Rare Disease Day, we’d like to highlight a couple of examples of model organism studies aiding the search for new therapies.
The yeast Saccharomyces cerevisiae has long been a powerful tool for studying the workings of the cell. As a eukaryote, S. cerevisiae shares many genes with humans and other animals, but it is a single-celled organism, so it can be more rapidly studied. Investigations in yeast demonstrated that a gene that is overexpressed in the aggressive childhood cancer rhabdomyosarcoma results in chromosomal instability. This instability made the yeast cells sensitive to drugs that are histone deacetylase inhibitors. Thanks to these insights from yeast, FDA-approved drugs in this class could one day prove useful for treating this rare cancer.
Clues to a treatment for Duchenne muscular dystrophy (DMD), an uncommon but severe disease, were uncovered using the zebrafish Danio rerio. Zebrafish can be grown quickly and boast transparent embryos that provide a remarkable window into body development. The zebrafish model of DMD harbors a premature stop codon in the homolog of the gene dmd, mimicking the human disease. This model led to the discovery that treatment with ataluren, an antibiotic, can promote read-through of this mutant stop codon. In 2014, ataluren was approved for clinical use in DMD by the European Medicines Agency.
Yeast and zebrafish have even been used in concert to identify new ways to treat rare disease. Mutations in the gene SLC25A38 cause a form of congenital sideroblastic anemia that has no effective treatment. This gene’s function remained unknown until studies in yeast showed that it transports glycine into the mitochondrion for heme synthesis. Giving mutant yeast extra glycine allowed them to produce heme at normal levels, “curing” the yeast version of the disease. However, extra glycine did not rescue heme production in zebrafish with a homologous mutation. It turns out that this disparity was due to different folate pathways in the two models. Yeast are able to synthesize folate on their own, whereas animals, like zebrafish and humans, must consume it in their diet. Giving the mutant zebrafish both glycine and folate restored heme production. These results suggested a new avenue for treatment using simple nutrients, rather than costly drugs. Further studies of the pathway in another model organism, the mouse, may reveal more about how to translate this treatment from the fish tank to clinic.
CITATION:
Science Writing and Communications Intern, Genetics Society of America.
View all posts by Marisa Wexler »Read more in
-
Early Career Leadership Spotlight: Julio Molina Pineda
We’re taking time to get to know the members of the GSA’s Early Career Scientist Committees. Join us to learn more about our early career scientist advocates. Julio Molina Pineda Policy and Advocacy University of Arkansas Research Interest My research interests focus on using model organisms to genetically dissect complex traits related to human disease. My…
-
Early Career Leadership Spotlight: Peiwei Chen
We’re taking time to get to know the members of the GSA’s Early Career Scientist Committees. Join us to learn more about our early career scientist advocates. Peiwei Chen Accessibility Subcommittee California Institute of Technology Research Interest Far from a harmonious place, the genome is a battleground, where every bit of DNA fights for inheritance and…
-
#Dros23 GSA Poster Award winners
We are pleased to announce the GSA Poster Award winners from the 64th Annual Drosophila Research Conference! Undergraduate and graduate student members of the GSA were eligible for the awards, and a hard-working team of postdocs volunteered their time as judges. Congratulations to all! Undergraduate Students 1st Place: Sofia Karter Lopez, University of Toronto “Rab11 mediates E-cadherin recycling during…
-
Congratulations to the Fall 2022 DeLill Nasser Awardees!
GSA is pleased to announce the recipients of the DeLill Nasser Award for Professional Development in Genetics for Fall 2022! Given twice a year to graduate students and postdoctoral researchers, DeLill Nasser Awards support attendance at meetings and laboratory courses. The award is named in honor of DeLill Nasser, a long-time GSA supporter and National Science Foundation…
-
New editors join GENETICS, G3 editorial boards
Several new editors are joining the GSA Journals. We’re excited to welcome Ricardo Zayas to the GENETICS editorial board under the Molecular Genetics of Development section, and on the G3: Genes|Genomes|Genetics board, we welcome Polly Campbell, Kevin Vogel, Joe Parker, and Ricardo Mallarino. Ricardo Zayas Associate Editor Ricardo Zayas is a Professor of Biology at…
-
Worms and Flies Provide Key Clues to Medical Mystery
This article is part of a series of posts outlining the history and impact of research in experimental organisms. The series is developed in collaboration with the GSA Public Communications and Engagement Committee. By the time Bertrand Might was six months old, it was clear something was amiss. His muscles weren’t developing normally; he was…
-
Congratulations to the 2023 Early Career Leadership Program Cohort!
The Genetics Society of America (GSA) is excited to announce the latest cohort of student, postdoc, and early-career research leaders joining the Early Career Leadership Program. Participants receive training and mentoring while serving on committees charged with understanding the needs, interests, concerns, and challenges of early career scientist members of the GSA. As part of…
-
GSA LOCI: Local Outreach Community Initiatives @ GSA Conferences
Highlights: Local Outreach Community Initiatives (LOCI): The Genetics Society of America is committed to supporting the communities of the host cities of our conferences. This new year, we are excited to reconnect with our GSA community in meaningful ways within and beyond our existing programming. The GSA membership has created a caring and supportive environment…
-
New members of the GSA Board of Directors: 2023–2025
We are pleased to announce the election of five new leaders to the GSA Board of Directors: 2023 Vice President/2024 President Mariana Wolfner Distinguished Professor of Molecular Biology and Genetics and Stephen H. Weiss Presidential Fellow My research has focused on the genes and pathways that mediate sexual development and reproduction, primarily in Drosophila. From…
-
Lance David Miller: Lighting Your Own Fire by Finding the Right Resources
By Daniel J. Gironda In the Paths to Science Policy series, we talk to individuals who have a passion for science policy and are active in advocacy through their various roles and careers. The series aims to inform and guide early career scientists interested in science policy. This series is brought to you by the…
-
Graça Almeida-Porada: The Importance of Communication in a Technologically Advancing World
By Daniel J. Gironda In the Paths to Science Policy series, we talk to individuals who have a passion for science policy and are active in advocacy through their various roles and careers. The series aims to inform and guide early career scientists interested in science policy. This series is brought to you by the…