Sleep Restriction Therapy for Drosophila Models of ALS & FTD

Students

Faculty

Assistant Professor of Psychiatry, Physician-of-Record

Project Summary

The fruit fly, Drosophila Melanogaster, is a powerful model for studying sleep.  Recent work suggests a bidirectional relationship between sleep and neurodegeneration: sleep is not only worsened by the accumulation of misfolded protein, but also contributes to this accumulation. This suggests sleep as a modifiable risk factor in the progression of neurodegenerative diseases.

The Kayser Lab developed a behavioral paradigm for modeling sleep therapy in Drosophila, called Sleep Restriction Therapy (SRT). By restricting sleep opportunity, sleep becomes more efficient. We developed a fruit fly model of Amyotrophic Lateral Sclerosis (ALS) by overexpressing TDP-43, the major protein contributing to this disease. This caused significant sleep deficits.

The goal of this project is to use sleep as a platform to identify genetic modifiers of TDP-43. We also want to test if SRT can improve the toxicity caused by TDP-43 overexpression.

We used the Drosophila Activity Monitoring (DAM) System to measure sleep and analyzed it using custom software. We then identified suppressors (those that caused increased sleep ) and enhancers (those that caused decreased sleep) of tdp-43 toxicity. We quantified sleep data and compared between the normal LD 12:12 and SRT 16:8 conditions.

We then performed survival assays and climbing assays as a proxy for health on both conditions. What we found is that SRT not only improved sleep efficiency, but also led to an increase in lifespan for some of our suppressors of toxicity.

This summer has been an amazing opportunity to dive into research. I have learned to appreciate behavioral therapies as a form of potentially treating neurodegenerative disorders. I don’t know yet how I will fit research into my career plans, but I sure know I must include it. This experience has stimulated my curiosity and desire to learn more.