Josie Mitchell Research Interests
While studying proteins in vitro (in a tube) helps define our understanding of individual protein characteristics, studying proteins in vivo (in an organism) reveals novel insights on how a protein functions within complex systems. My research uses genetic tools, including RNAi and CRISPR-Cas9 genome engineering, to manipulate and study protein function and localization in vivo using Drosophila melanogaster (fruit flies).
One ongoing project investigates transporters involved in chronic kidney disease and kidney stone formation. Chronic kidney disease is a public health concern with limited treatments. Kidneys rely on precise localization and regulation of transporter proteins and ion channels to mediate transport of solutes, water homeostasis, and excretion of toxins. Understanding the molecular mechanisms regulating kidney function is important for developing therapeutics for kidney diseases, however human kidneys are not easily studied at the biochemical level. The Drosophila Malpighian (renal) tubules are a compelling disease-model to study the biochemistry of kidney dysfunctions as they are functionally similar to human nephrons: the component of the kidney that filters, absorbs, and secretes ions, water, and toxins. We use CRISPR-Cas9 genome engineering to fluorescently tag and manipulate conserved renal transporters to uncover mechanisms important for their trafficking and function.
Another ongoing project investigates the localization and function of an evolutionarily conserved gene and its protein product’s role in inhibiting protein aggregation. Protein aggregation can cause disease and is a hallmark of neurodegenerative diseases like Alzheimer’s and Parkinson’s disease. Our work seeks to characterize the localization and function of this protein in flies to better understand its role in inhibiting protein aggregation.