We share 75 percent of the genes that cause disease in human beings with the humble Drosophila fruit fly. Dr. Daniela Zarnescu and her lab exploit this remarkable fact to more quickly find promising research leads within the relatively simple fly model, leads that could translate into better treatments for and understanding of ALS (Amyotrophic lateral sclerosis, or Lou Gehrig’s Disease), other neurodegenerative diseases, and the effects of aging.
Zarnescu's new paper in Cell Reports shows that when a specific protein chaperone is altered in motor neurons from flies, mice and patients, restoring its expression in flies improves defects in synaptic function, mitigates locomotor defects and increases lifespan. Read the paper.
Zarnescu lab graduate student Ernesto Manzo is a Howard Hughes Medical Institute Gilliam Fellow for 2016-2019. He presented his recent work on metabolic defects and the potential benefits of a high-sugar diet for ALS patients at HHMI on September 28.
“Understanding the basic science is really important,” Zarnescu emphasizes in explaining her lab’s quest to learn more about how ALS, a disease that affects approximately 20,000 Americans, leads to loss of muscle control and movement. “As is understanding how we can make a quick impact.”
Zarnescu’s lab seeks both to learn more about how ALS and other forms of neurodegeneration play out on a molecular level and what treatments might ameliorate or reverse the effects of these diseases. Her recent paper in Cell Reports, “Post-transcriptional inhibition of Hsc70-4/HSPA8 expression leads to synaptic vesicle cycling defects in multiple models of ALS” focuses on a key protein affecting motor neurons in ALS. The lab’s commitment to helping ALS patients extends beyond research; Zarnescu and her team will be participating in the annual ALS Association’s Tucson Walk to Defeat ALS on October 7.
One of two graduate students in her lab, Ernesto Manzo is turning his attention to how glial cells are affected by ALS. While they take up as much space as neurons in the human brain, little is known about the role of these insulator cells in the neurodegeneration associated with ALS, which is fatal within 2-5 years of diagnosis. With the help of the fruit fly, Manzo can gather data quickly to look both at the mechanisms of the disease, as well as identifying promising therapies.
Manzo was awarded the prestigious Howard Hughes Medical Institute Gilliam Fellowship for 2016-2019, and presented his work on metabolic defects and the potential benefits of a high-sugar diet for ALS patients at HHMI on September 28.
Support from NIH, the Muscular Dystrophy Association, Arizona Biomedical Research Commission, private donors, student fellowships, and collaborations with pharmaceutical companies and departments like pharmacy and chemistry come together in Zarnescu’s thriving lab. However, Zarnescu faces the same challenge every time she seeks out a new partnership—explaining the very simplicity that is the advantage of Drosophila. “I always have to convince people of the validity of the fly model.”
Fortunately, there is plenty of evidence that Drosophila is a “fruitful,” and flexible, initial platform to study human disease, including an FDA-approved treatment for thyroid cancer that was initially identified in fly experiments. Having to prove the viability of her model inspired Zarnescu to create a course (MCB 482/582) to teach U of A students more generally about the value of developing simple models, where various mutations can be replicated and tested and potential treatments can be assessed quickly in the laboratory.
“This is where the fly magic happens,” Zarnescu says, smiling as she stops at the workstations in her own lab where a post-doc, two graduate students, and 16 undergraduate students are testing drugs and molecules. Much of the magic is due to the hard work and dedication of a large undergraduate research team. Zarnescu is quick to praise the quality of MCB students.
“Undergraduate students make MCB special—when they get excited about what they are doing, they can really go the distance. Not just for the lab, but for themselves,” Zarnescu enthuses. “If someone contributed data that makes the paper happen, they will see their name on it.”
Having more senior undergraduate students mentor newer ones has been important to the lab’s success. Beckman Scholar Stephen Yao, a senior in his fourth year working in Zarnescu’s lab, runs a research project, including guiding and mentoring newer students on the team. Zarnescu recommends research to any undergraduate. “Get engaged as soon as possible and try different things…. Research shows you how to solve problems, whether or not you want to be a researcher.” In her lab, it also teaches you how to be a leader.
When Zarnescu isn’t exploring therapies for ALS or the correlation between neurodegeneration and aging, she takes time out for the arts. She can be found at the opera, ballet, or enjoying an art show (the fly art on her lab walls doesn’t count).