As we age there are a number of physiological changes that take place. In particular, we know that there is a decline in metabolism and mitochondrial function. In addition to this, we know that there is a age-related sleep decline. It has also been shown that sleep dysfunction leads to metabolic dysfunction. Dr. Deal hypothesizes that mitochondria are the middle man between age and sleep decline. She plans to investigate is improving mitochondrial health can rescue age-related sleep phenotypes. In addition to this, some fruit fly mutants that have reduced sleep also have shortened lifespans. Her lab will investigate if improving mitochondrial health will improve sleep or lifespan or both in these flies. 

Dr. Deal identified PolG1 as a candidate for sleep regulation during her time as a postdoctoral fellow. PolG1 is a mitochondrial polymerase that is important for transcribing the 13 protein coding genes and 22 tRNAs and 2 rRNAs found in mtDNA, and it is implicated in multiple diseases. She found that loss of PolG1 in neurons led to an age-related loss of sleep along with hyperactivity. She hypothesizes that this is due to a build up of reactive oxygen species that alters activity and sleep through lipid oxidation. However, it could also be due to starvation. We are actively exploring the potential mechanism. We are also going to be looking into why this is an age-related phenotype. Is there a susceptibility as we age that leads to this phenotype? 

Mitochondrial diseases are diseases caused by a genetic mutation that affects mitochondrial function. These diseases have been difficult to identify in the past because they can often have a lot of heterogeneity in the strength of their phenotypes. However, sequencing has lead to an explosion in the number of genes that cause mitochondrial disease with more than 450 genes now identified. However, these genes are often understudied because they are already classified as mitochondrial genes. We hypothesize that investigating genes with distinct mitochondrial functions will cause distinct phenotypes, which is why there is heterogeneity in patient phenotypes. Using Dr. Deal's experience in human genetics studies, we would like to systematically investigate distinct classes of mitochondrial genes and their role in behavior. We will go on to examine if patient genetic variants have functional consequences.