Gerben van Ooijen

Circadian rhythms

We all experience daily cycles in light/dark and temperature, resulting from planet Earth’s rotation around its axis. These daily changes profoundly influence many aspects of cellular and organismal life, and have driven the evolution of an endogenous circadian clock to adapt to, and anticipate this rhythmicity. In
virtually all living organisms on earth, this circadian clock times cellular processes to the appropriate time of day. For example, the circadian clock in photosynthetic organisms is important to anticipate the duration of the night, and regulate gradual release of energy captured during daylight; this regulation protects the organism from starvation towards the end of the night. Behavioural rhythms such as the sleep/wake cycle in animals are also under strong circadian control to reflects the organism’s lifestyle, for instance to temporally separate activity from times with high risk of predation.


A non-transcriptional circadian oscillator

Until recently, circadian rhythms were thought to originate from rhythmic transcription of clock genes, that feed back to regulate their own expression. Indeed, transcriptional/translational feedback loops (or TTFLs) between clock genes are essential to drive the set of clock outputs that deliver the adaptive advantage of having a timekeeping mechanism. The absence of any homology between these oscillating clock genes across higher taxa led researchers to believe that clocks had evolved multiple times during evolution. However, we have recently discovered circadian oscillations that persist in the complete absence of any transcription in green algae (O’Neill, van Ooijen, et al., Nature 2011). Although it is currently unclear what constitutes this non-transcriptional oscillator (NTO), it was known that it was conserved between algal and human cells (O’Neill et al., Nature 2011) and we have now demonstrated conservation of the identified rhythmic marker across life from all evolutionary kingdoms (Edgar et al., 2012) including plants, animals, fungi, and even Archaea. Together, these studies constitute a major paradigm shift for clock research, and we now strive to identify what exactly constitutes the conserved non-transcriptional proto-clock.


Circadian regulation of immune responses

Clock disruption in humans, for example by genetic defects or present in the estimated 14% of the UK workforce currently on shift work, increases the incidence of metabolic syndrome, diabetes, cancer, depression and neurodegenerative disorders. In model organisms, clock mutants have been shown to have more severe disease symptoms and to be generally more susceptible. In plants however, relatively little is known about how circadian clocks affect health. Plants are, like us, under constant attack from a diverse range of potentially pathogenic organisms. Disease is a relatively rare occurrence because plants posses an intricate immune system. However, losses of crop plants due to disease are large, and chemical prevention of disease is highly inefficient, and economically and environmentally costly. With the world's population increasing, the global demand for food will drastically rise. In addition, demand of plant-based energy production is increasing, as emission of greenhouse gasses resulting from the use of fossil fuels needs to be reduced in order to slow down global warming. Possible involvement of circadian clocks in plant health has not been studied in any detail, and given its importance for sustained wealth of the human species, we employ a combination of plant pathology and circadian biology methods to study what aspects of plant immunity are circadially regulated.


Model organisms: Arabidopsis thaliana and Ostreococcus tauri

Over the past decades, Arabidopsis thaliana has been the chosen model plant for scientific research into plant development, evolution, and immune responses, similar to the role that mouse or fruit-fly serves as a model organism
for animal biology. As a result, large collections of mutants and resources are available, and the majority of our projects employ these tools to efficiently study circadian clock interaction with immune pathways in plants. However, several problems exist with Arabidopsis as a model organism. Cellular, tissue and whole organism complexity in flowering plants can complicate studies into basic cellular functions. Secondly, the high level of genomic redundancy affects genetics and functional protein biochemistry. The novel model organism Ostreococcus tauri, a species of unicellular marine algae, is the smallest known eukaryote and possesses a greatly reduced cellular complexity, manifested by the presence of just one of most organelles (mitochondrion, chloroplast, golgi stack) per cell. Combined with a genome containing only ~8000 genes, this organism provides a platform to perform rapid experimentation in a simpler species. Using methods technically not feasible in a background of vast complexity, this generates hypotheses testable in Arabidopsis, substantially accelerating our research.
 
 

Research