Hodge, Rachel
Rachel is in the Cell and Developmental Biology home area of the MBIDP, and joined the CMB training program in 2018. She received a B.S. degree in Biochemistry and Cell Biology from Rice University.
Mentor: Dr. Leanne Jones
Intestinal function declines with age and is associated with loss of intestinal barrier function across species. Loss of barrier function in mammals is correlated with decreased integrity of intestinal occluding junctions. Occluding junctions in the intestine regulate flow of water, ions, and nutrients while preventing microbes and toxins from leaking into interstitial tissue. In Drosophila melanogaster, severe loss of barrier function is associated with death, although the age-related causes of barrier dysfunction are unknown. Data from our lab have shown that gaps appear in septate junctions (SJs) of aged Drosophila midgut epithelia, likely due to separating membranes between adjacent cells. SJ structural proteins such as Gliotactin (Gli), Snakeskin (Ssk), Coracle (Cora), and Mesh, which are important for maintaining intestinal barrier function, become mis-localized with age, which could be one explanation for the loss of barrier function over time. I hypothesize that these age-related changes in SJs are due to improper junction assembly.
To address the mechanism of age-related changes in SJ protein localization, I will identify proteins that co-localize with SJ proteins in young and aged flies using proximity tagging, coupled with mass spectrometry. In addition, I will perform immunofluorescence with well-characterized antibodies and transgenic tools to identify cytoplasmic compartments that contain SJ proteins in young and aged flies. Using conditional loss-of-function approaches, such as temperature or drug-inducible RNAi expression, I will deplete candidate proteins that may be responsible for proper SJ protein assembly to test whether this will disrupt SJ protein localization and function–recapitulating aging phenotypes. I predict that my findings will be key in elucidating the relationship between aging and occluding junction functional decline. Identification of factors involved in age-related intestinal barrier decline will advance understanding of age-related intestinal dysfunction and gastrointestinal diseases.
