Aging and sleep are highly conserved biological processes, and deficiencies and disruptions in sleep and aging processes have been linked with many other diseases including obesity, diabetes, and cancer. Basic research on sleep and aging will not only provide a better understanding of their fundamental functions and underlying mechanisms, but it may also simultaneously help us understand their interactions to various other disorders. Studying the molecular components and neural circuits using a simple model organism such as Caenorhabditis elegans, with a completely mapped genome and nervous system and its various tools to interrogate gene and brain functions, will allow use to more directly examine sleep and aging processes, and provide significant insights into big questions such as why do we sleep, or how do we extend healthy lifespan?
The roundworm Caenorhabditis elegans is particularly suited for studying aging and sleep. It displays all behavioral hallmarks of sleep behavior as in humans, and its nervous system physiology is remarkably different between sleep and wake states. Many anatomical and functional changes that are observed in human aging are also seen in C. elegans. Its short life span of about three weeks and a rapid 2-3 day life-cycle coupled to its small size, allows for easy genetic manipulation and high-throughput screening of mutations in worm genes with altered sleep and aging phenotypes. Worm genes show strong homology with their human counterparts, particularly in genes that regulate sleep and aging. Many fundamental discoveries have been made with C. elegans such as RNA interference and genetic regulation of programmed cell death, and it likewise is a valuable discovery system for sleep and aging research.
Sleep and metabolic processes are intricately connected, and this association has important clinical implications; for example, short sleep is associated with obesity and type-2 diabetes. We investigate the genes and neurons that govern these sleep-metabolic interactions. Our recent studies have shown that the conserved salt-inducible kinase 3 (SIK3) pathway plays an important role in the metabolic regulation of different sleep states of C. elegans, such as developmentally-timed sleep (analogous to circadian sleep) and stress-induced sleep (analogous to sickness sleep). SIK3 proteins and their targets in worms, mice and human are highly conserved. Currently, we are investigating how SIK3 coordinates sleep-metabolic interactions using genetic and neural approaches as well as high-throughput behavioral analyses, and why this pathway is important for health.
Our lab is also interested in studying organismal aging, which could involve the progressive accumulation of deleterious molecular changes that could lead to age-related declines and diseases. We investigate a newly appreciated class of non-coding endogenous RNAs, called circular RNAs, which are mostly generated by back-splicing events from known protein-coding genes. Our recent studies have shown that these circRNAs show a progressive and massive accumulation during aging on a genome-wide level in C. elegans. No clear function is known for these age-accumulated circRNAs, or for most of the thousands of circRNAs discovered. Currently, we use next-generation sequencing approaches, genome-editing, and behavioral analysis to uncover regulatory mechanisms and functions of circRNAs in aging, and their possible role in age-related diseases.
Lastly, our lab is broadly interested in understanding the effects of environmental and internal signals on behavior and gene expression. We have published several papers on dynamic changes in olfactory gene expression depending on the feeding state of the free-living nematode C. elegans, which could potentially gain insight into how parasitic nematodes and disease-carrying insects seek out and leave their host based on their nutritional status.
If you are interested in our research, and wish to join the lab or do a research rotation, then please contact Dr. van der Linden at email@example.com. The lab accepts graduate students from the Molecular Biosciences and Integrative Neuroscience Graduate Programs. If interested in studying behavior of natural C. elegans isolates, Dr. van der Linden's lab also accepts graduate students in the Ecology, Evolution and Conservation Biology Graduate Program.
Current research interests
- Neurogenetics of sleep and aging
- Sleep-metabolic Interactions
- Non-coding RNAs in aging
- Diet effects on behavior and neural gene expression
- Ph.D., Biology, Hubrecht Institute, University of Utrecht, The Netherlands, 2003
- M.Sc., Molecular Biology, University of Leiden, The Netherlands, 1999
- B.Sc., Biochemistry, Poly Technical College of Delft, The Netherlands, 1996
- B.Sc., Microbiology, Van Leeuwenhoek Institute, The Netherlands, 1993
- 2016-present, Associate Professor, University of Nevada, Reno, NV
- 2009-2016, Assistant Professor, University of Nevada, Reno, NV
- 2003-2009, Postdoctoral Fellow, Brandeis University, Waltham, MA
Please find a complete list of published work here: My Bibliography