The single-celled fungus allows researchers to study Alzheimer’s, Parkinson’s, ALS and other brain diseases with unparalleled speed and scale.


new era in research on Friedreich’s ataxia, a rare, fatal neurodegenerative disease, began in 1996 when, 133 years after the disease was first characterized, researchers showed it is caused by mutations in the gene now known as FXN. While this finding was an important advance, it also presented researchers with the daunting task of determining why neurons with FXN mutations were dying in Friedreich’s ataxia patients. To meet this challenge, a team at the University of Utah turned to an unlikely source: the baker’s yeast Saccharomyces cerevisiae. A mere 15 months later, using genome editing, growth assays, and biochemical techniques, the Utah team demonstrated that FXN mutations cause fatal mitochondrial damage. This finding identified an important therapeutic target, and clinical trials have recently demonstrated that two drugs targeting mitochondrial function improve symptoms in Friedreich’s ataxia patients.

This serves as one of the earliest examples in which yeast, a single-celled fungus with a one-week lifespan, provided actionable insights into a complex, age-related disorder of the billions of interconnected neurons of the human brain. But remarkably, such stories are common in neurodegenerative disease research, and not just for rare diseases like Friedreich’s ataxia, but for more common diseases as well, including Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis (ALS). Yeast have long been used to understand the fundamental cellular, molecular, and genetic features common to all forms of eukaryotic life and how disrupting these features leads to disease.

Humans and yeast share not only a common set of cellular structures and functions, but also a set of genetic instructions that encodes them.

After S. cerevisiae became the first eukaryotic organism to have its genome fully sequenced in 1996, researchers determined that 60 percent of yeast genes have a human homolog. This means that humans and yeast share not only a common set of cellular structures and functions, but also a set of genetic instructions that encodes them. Neurodegenerative diseases are likely caused by genetic and environmental factors that impair fundamental biological processes conserved across eukaryotic life, and yeast can serve as a valuable model for understanding the roles of these factors in disease and developing interventions to counter their deleterious effects.

Yeast provide neurodegenerative disease researchers with unique advantages compared to other model systems. First, yeast cells grow faster and can be maintained at a fraction of the cost of other eukaryotic organisms. This allows researchers to complete experiments faster and at greater scale than in other systems. Moreover, yeast growth provides a simple and reliable indication of cellular health. In the context of neurodegenerative disease research, this provides a metric to decipher the environmental and genetic factors that cause neuronal death and to screen therapeutics intended to treat or prevent these diseases. And arguably the greatest advantage of yeast is the ease with which it can be genetically modified. Yeast, more than any other eukaryotic organism, readily incorporates foreign DNA into its own genome by the process of transformation. This enables researchers to add and remove native yeast genes, incorporate DNA from other species into yeast, and control gene expression, among many other applications.   



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