Investigating The Regulation And Role Of P38 Mapk In Collagen-Related Limb Girdle Muscular Dystrophy

Aging is an expected and normal process across living organisms. It is characterized as a loss of stress resistance, degeneration of tissues, and decline in motor function that happen gradually across lifespan. Susceptibility to neurodegenerative and dystrophic conditions also increase, and unlike aging, are not a normal aspect of lifespan. Discerning the difference between normal and aberrant aging states will give insight into the mechanisms behind the progressive dysfunction shared among organisms. Previous work in our lab has shown that the aging gene p38 MAPK in Drosophila melanogaster plays a significant role in the aging process through its downstream effects on nuclear and cytoplasmic targets, specifically through the regulation of protein turnover and response to oxidative stress. Through a proteomics analysis of p38Kb mutants across different ages, we found that levels of the extracellular matrix protein collagen IV varied significantly with p38Kb manipulation. We will explore the nature of this relationship and determine if loss of p38Kb results in aggregation of collagen IV, a loss of muscle structure, or impairment of collagen IV trafficking across the plasma membrane. Additionally, we will determine if loss of collagen IV results in increased oxidative stress and a decrease in lifespan