Human Charged Multivesicular Body Protein 2B (CHMP2B) Causes Deficits in Morning Circadian Activity when Expressed in Drosophila Clock Neurons
Date of Award
Honors Thesis (Colby Access Only)
Colby College. Biology Dept.
S Tariq Ahmad
Circadian rhythms govern the 24-hour sleep-wake cycle found in most organisms including humans and Drosophila. Patients with frontotemporal dementia (FTD) commonly experience deficits in circadian rhythm functioning. To investigate the basis of this, I misexpressed a mutant isoform of the charged multivesicular body protein 2B (CHMP2BIntron5) found in human FTD patients in two subsets of the Drosophila circadian pacemaker neurons (CPNs) using the GAL4-UAS system. The first subset targeted were CPNs responsible for the morning activity period (pdf-GAL4) and the second for morning and evening activity periods (cry-GAL4). Using this model and genetic ablation models I was able to assess the circadian activity of flies as well as image the brains of these flies while fluorescently marking the CPNs. Through these experiments I observed that CHMP2BIntron5 expressed in Pdf or Cry CPNs resulted in loss of morning activity without causing cell death. I furthermore observed the absence of a morning period caused by ablating pdf cells and the absence of both morning and evening peaks resulting in arrhythmic behavior caused by ablating cry cells. This indicates a heightened sensitivity to CHMP2BIntron5 pathology in the Pdf morning cells. Molecular analyses to determine what is causing this disruption are forthcoming.
FTD, Dementia, Circadian Rhythms, Drosophila
Recommended CitationKrasniak, Christopher, "Human Charged Multivesicular Body Protein 2B (CHMP2B) Causes Deficits in Morning Circadian Activity when Expressed in Drosophila Clock Neurons" (2016). Honors Theses. Paper 828.