VAN DER LINDEN LAB
Neurogenetics of Sleep and Aging
Metabolic regulation of sleep
NIH NINDS (R01 NS107969)
The high prevalence of coexistent sleep and metabolic disorders suggest that these processes are integrated at the molecular level, but mechanisms of this integration are unknown. Our previous work showed that a Salt-Inducible Kinase (SIK) related to AMPKs in the nematode C. elegans (called KIN-29) directly phosphorylates and antagonizes the function of a class II Histone Deacetylase (HDAC4). SIK-mediated control of class II HDACs is highly conserved between worms, flies and mammals, where it plays critical roles in fat metabolism and feeding-state responses. In collaboration with Dr. David Raizen (University of Pennsylvania, Perelman School of Medicine), we have shown that the KIN-29/SIK is a key node in connecting sleep and metabolic homeostasis. We are currently studying the role of KIN-29/SIK in the regulation of sleep and its interactions to metabolism, which has the unique potential to investigate the link between sleep disorders and metabolic syndromes.
Measuring quiescence behavior of C. elegans using a WorMotel:
The role of circular RNAs in aging and age-related diseases
NIH NIA (R21 AG058955)
Aging involves the progressive accumulation of deleterious molecular changes that leads to age-related physiological declines and diseases. A newly appreciated class of non-coding RNAs are circular RNAs (circRNAs) that are abundantly expressed from nematodes to humans. RNA-seq studies have found that circRNAs accumulate during aging in mice and Drosophila, suggesting that these age-associated changes in circRNA expression may influence lifespan. The nematode C. elegans is a premier genetic model organism for aging research with a relatively short lifespan, and has many advantages for investigating the regulation and function of circRNAs in organismal aging. In collaboration with Dr. Pedro Miura (Biology Dept), we found for the first time that hundreds of circRNAs accumulate during C. elegans aging. Interestingly, circRNAs that are highly accumulated include those derived from genes that play a conserved role in lifespan regulation in both mammals and in C. elegans. Our lab in collaboration with the Miura lab is currently studying the function of circRNAs in C. elegans aging. Changes in circRNA levels with advancing age may provide critical insights into aging and age-related diseases such as Alzheimer's disease.