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|2013-||Professor, Chair of Plant Biology||Department of Biology, University of York|
|2008- present||Research Group Leader, guest status from 2013||Plant Developmental Biology, Max Planck Institute for Plant Breeding Research, Köln, Germany|
|2002-2008||Project Leader||Plant Developmental Biology, Max Planck Institute for Plant Breeding Research, Köln, Germany|
|2000-2002||Research Fellow||Department of Biological Sciences, University of Warwick, Coventry, UK|
|2001||Visiting Scientist||Institute of Plant Biology, Szeged, Hungary|
|2000||Research Associate with Dr. Richard D. Vierstra, Program in Cellular and Molecular Biology||University of Wisconsin-Madison, Madison WI, USA|
|1994-2000||Research Assistant||University of Wisconsin-Madison, Laboratory of Genetics, Madison WI, USA|
|2008-2009||academic degree for equivalency of Associate Professorship status||University of Bonn, Bonn, Germany (Habilitation in Genetics)|
|1994-2000||Ph.D. in Genetics||University of Wisconsin-Madison, Madison, WI|
|1991-1994||B.S. in Molecular Biology and Microbiology, Minor in Chemistry, Graduated Magna cum Laude||University of Central Florida, Orlando|
Plants experience daily and seasonal changes in light and temperature. Processing these signals is key for fitness. To anticipate rhythmic changes, plants have evolved a timing mechanism termed the circadian clock. Our working group is engaged with i) defining the framework of the core-clock mechanism, ii) initiating a mechanistic understanding of light and temperature inputs to this oscillator, and iii) characterizing various outputs from this timer under simulated and natural field conditions.
Circadian clocks are prevalent timing mechanisms used to predictably adjust physiology. In plants, this clock regulates a suite of developmental and metabolic processes. In fact, around >30% of all transcripts have been found to be clock regulated. In this way, this circadian timer drives molecular outputs in the establishment of fitness in physiological processes, which include developmental timing and hormone signaling. Collectively, our work is consistent with the view that integrated processes drive output timing mechanisms.
We tested mathematical models of CCA1/LHY-TOC1 as the core oscillator. It was found to be obligate to sustain rhythms (Ding et al. 2007b). From this, we examined how light serves as a major Zeitgebers (time-giver) of entrainment (Kolmos and Davis 2007a; Feher et al. 2011). Our analyses of ELF4 suggested that it is a positive regulator of CCA1 (Doyle et al. 2002). We then refined the placement of ELF4 in the clock (McWatters et al. 2007), and hypothesized that ELF4expression is interlocked with the CCA1/LHY-TOC1 loop (Kolmos and Davis 2007b). This was also found to be true in a tropical plant not thought to be selected for a photoperiodic lifestyle (Adeyemo et al. 2011) and temperate barley (Campoli et al. 2012; Faure et al. 2012).
As ELF4 lacks sequence similarity to known domains and functional homologues had not yet been identified, we solved a structure and showed that ELF4 resolves to an electrostatic interface (Kolmos et al. 2009; Adeyemo et al. 2011). We supported this with expression analysis. We could mathematically model this effect (Kolmos et al. 2009). How ELF4 signals to the clock required identification of transcription factors that sustain the clock. For this, we measured clock phenotypes in hundreds of misexpression transcription-factors lines and numerous mutants were found with aberrant rhythms (Hanano et al. 2008).
We defined the circadian placement of the three arrhythmic mutants: elf4, elf3, and lux. We found that ELF4 binds to ELF3 and this restricts ELF3 to nuclear foci to activate it (Herrero et al. 2012a, Herrero et al. 2012b). RNA expression data was used to direct a mathematical position of ELF3 in the clock network (Kolmos et al. 2011; Herrero et al. 2012a). This predicted direct effects on the morning clock gene PRR9, and we could show that ELF3 can associate to a phylogenetically conserved region of the PRR9 promoter by recruitment of the GARP-type DNA-binding protein LUX (Herrero et al. 2012a) and that ELF3 function depends on haplotype and genomic context (Undurraga et al. 2012). Taken together, we defined a co-repressor protein complex pivotal to sustain the plant circadian oscillator, and this thus closed the evening arm of the clock. The clock can now be seen as a closed loop system.
Light-entrainment; metabolic entrainment as the mechanism? :
We previously isolated TIC and reported it to be required for dawn perception (Hall et al. 2003). To further investigate its function, we measured clock-gene expression in tic. Morning-clock genes were transcriptional targets. Epistasis confirmed this (Ding et al. 2007a). To start to understand its molecular mechanism, we isolated the TIC gene. It encodes a protein continuously present that it is strictly nuclear localized. We suggested that TIC is a morning-required nuclear-acting factor working close to the central oscillator (Ding et al. 2007a).
In as of yet unpublished work, in an attempt to define mechanistic features of TIC protein function, we performed an interaction screen and identified the metabolic-sensitive kinase AKIN10. We then found that this kinase can phosphorylate TIC. Epitasis genetics fully supported AKIN10 activation of TIC in the clock. This is consistent with our new hypothesis that basal metabolism serves in entrainment (Sanchez et al. 2011), and that this controls transcription factor stability (Shin et al. 2012).
Photoreceptor inputs to the clock: testing Aschoff's Rule entrainment as the mechanism
Physiologically, increases in light intensity result in decreases in circadian period: a process referred to as "Aschoff's Rule." In recent work (Kolmos et al. 2011), we uncovered a hypomorphic allele of ELF3 in a forward-genetic screen. This allele has a unique phenotype in that it displays light-dependent circadian phenotypes. To define the basis for this phenotype, we tested for, and found genetic interactions to phytochromes. We now can hypothesis a molecular basis for Aschoff's Rule; phytochromes inactivate the ELF3 circadian repressor. This was tested using natural resources and the results were consistent (Anwer et al. submitted)
A prelude to understanding temperature entrainment:
Light-dark and warm-cool are environmental cues that set the oscillator; these cues are called zetigebers. Differential responses of the oscillator were found dependent on the nature of the preceding zetigeber. We exploited natural-allelic variation to uncover periodicity loci that depend on respective thermal and photic entrainment. In various mapping populations, plants previously thermally entrained consistently displayed reduced period length, compared to matched lines that had received photic entrainment (Boikoglou et al. 2011). This work describes the concepts of thermal sensitivity (McClung and Davis 2010). Together, the zeitgebers of the preceding environmental direct future behavior of the circadian oscillator.
|Senior Research Technician||Amanda Davis||Galdieria genomics|
|Postdoctoral Research Associate||Dr. Rachael Oakenfull||Arabidopsis circadian mechanism|
|Ph.D. student||Jess Hargreaves||Wavelets in the circadian clock|
|Ph.D. student||Kayla Mccarthy||barley circadian clock|
|Ph.D. student||Jack Munns||worm circadian clock|
How to set a circadian clock: structural mechanism of ELF3-ELF4 clock-protein action in transcriptional repression (2015-16)
The circadian clock drives genome-scale transcription to coordinate most of growth and development. As the time the sun rises changes every day, mechanisms exist to reset this clock in a process called entrainment. Here a project is proposed to unravel the clock-resetting mechanism. Using a combination of biochemical and cellular experiments, one would examine the spatial-temporal function of the key hub protein ELF3. One would monitor the global, genome-wide binding of this chromatin-associated factor to define its transcriptional target genes. Next an exploration of where and how the ligand ELF4 activates ELF3, and how light-perception represses this, would be examined. Efforts to solve by crystallography the structure of the ELF4 / ELF3 repression complex will be undertaken and, in parallel, associated in vitro biophysics of complex assembly will be elucidated. Taken together this project is envisaged to provide the mechanistic basis of a clock-resetting mechanism in plants.
References: Anwer et al. eLife e02206 (2014); Herrero et al. Plant Cell 24: 428–443 (2012); Levdikov et al. Proc. Natl. Acad. Sci. USA 109, 5441-5445 (2012); Kolmos et al. Plant Cell 23: 3230-3246 (2011)
Co directors: Tony Wilkinson Department: Chemistry