Our NIH funded research studies the role of disruptions of zinc (Zn) homeostasis in the mechanism of cell death in the Alzheimer's disease (AD) brain. In particular, we are interested in two critical Zn transport proteins (ZnT-1 and ZnT-6) that function to export excess cytoplasmic Zn to the extracellular space (ZnT-1) or sequester Zn in the trans golgi network (ZnT-6). The undergraduate project will involve the use of existing neuroblastoma cell lines stably transfected to overexpress ZnT-1 or ZnT-6 to determine if elevated levels of the proteins lead to increased susceptibility to insults associated with the AD brain including amyloid beta peptide, 4-hydroxynonenal (a neurotoxic marker of lipid peroxidation) or hydroxyl radical generated by iron/hydrogen peroxide. The experiments will be carried out using insults alone or in combination with Zn. Under supervision by Dr. Lovell and senior research analyst Dr. Shuling Xiong, the NSF-REU student will learn sterile techniques for use with mammalian cell culture, how to establish and maintain neuroblastoma cell lines, and how to treat cultures and evaluate toxicity using UV-Visable spectroscopy. The student will also learn a variety of methods to assess cell survival and how to evaluate changes in protein expression using both Western blot analysis and laser confocal (fluorescence) microscopy. In the course of the project, the student will gain an understanding of techniques from cell/molecular biology and analytical instrumental chemistry. This project would be well suited for a student with interests at the interface of chemistry and biology and would likely appeal to students interested in pursuing medical careers.
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