1. + An innovative approach to studying Huntington’s Disease Caroline Fukawa Dr. McElwain, PhD

2. + Huntington’s Disease Neurodegenerative disorder Results in the involuntary movements of the body and lack of cognitive control

3. + Drosophila melanogaster Fruit Flies Why they are useful for studying Huntington’s Disease Figure 1. Cross sections through a normal and postmortem HD patient demonstrate dramatic degeneration. Cross-sections through the eye of the eye of fly expressing a protein similar to the huntingtin transgene show similar loss of neuronal tissue.

4. + Previous Studies Used the Drosophila model to study Huntington’s disease and have found there is degeneration in the phenotype of the fly (Marsh 2003) Studies use the whole organism, in-vivo, which is both costly and not time efficient Belgian scientists- discovered away to study brains of Drosophila in-vitro (Moseman 2008) Combination of these studies leads to my research question

5. + My Research Question Is it possible to study Huntington’s Disease in-vitro in the Drosophila model? Extract the brains from the Drosophila and see if they exhibit the same phenotype that they did in the in-vivo studies Make a comparison of 4 different brains: 2 control and 2 experimental 2 control: One Wild type brain and One Huntington’s Brain 2 experimental: Wild type brain treated with methylene blue and a Huntington’s brain treated with methylene blue Methylene blue has been proven to reduce the number of protein aggregates of the Huntingtin protein (in-vivo) Use immunofluorescent staining and a standard fluorescent microscope

6. + Wild Type Brain (No degeneration) Expected Results Huntington’s Brain (Significant degeneration) Wild Type Brain treated with Methylene Blue (No change) Huntington’s Brain treated with Methylene Blue (Decrease in degeneration) *The colored lines are representative of the amount of degeneration that occurs

7. + Expected Results Cont’d Expected Results- similar to the in-vivo studies; reduction of aggregates Advantages- more cost effective, test possible cures/treatments for the disease faster and more readily Figure 2: Immunofluorescent staining in Drosophila brains

8. + Works Cited Egger, Boris, Lena Van Giesen, Manuela Moraru, and Simon G Sprecher. "In Vitro Imaging of Primary Neural Cell Culture from Drosophila." Nat Protoc Nature Protocols (2013): 958-65. "Huntington Disease." Genetics Home Reference. 1 June 2013. Web. 27 Oct. 2015. "Huntington's Disease." Mayo Clinic. Mayo Clinic, 14 July 2014. Web. 26 Oct. 2015. "Nearly 1 in 6 of World's Population Suffer from Neurological Disorders – UN Report." UN News Center. UN, 27 Feb. 2007. Web. 28 Oct. 2015. Marsh, J. L., J. Pallos, and L. M. Thompson. "Fly Models of Huntington's Disease." Human Molecular Genetics (2003). Moseman, Andrew. "Fruit Fly Brains Stay Alive in a Dish, Teach Us About Nerve Damage - Discoblog." Discover: Science for the Curious. Kalmbach Publishing Company, 5 June 2008. Web. 10 Oct. 2015. a Sontag, E. M., G. P. Lotz, N. Agrawal, A. Tran, R. Aron, G. Yang, M. Necula, A. Lau, S. Finkbeiner, C. Glabe, J. L. Marsh, P. J. Muchowski, and L. M. Thompson. "Methylene Blue Modulates Huntingtin Aggregation Intermediates and Is Protective in Huntington's Disease Models." Journal of Neuroscience (2012): 11109-1119.