Charalambos P Kyriacou

Charalambos P Kyriacou
University of Leicester | LE · Department of Genetics

BSc PhD

About

276
Publications
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11,777
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Additional affiliations
March 2009 - September 2009
University of Padova
Position
  • Professor

Publications

Publications (276)
Chapter
The use of nonclassical model organisms for biological rhythm research has become popular in the last two decades. Here we describe techniques for delivery of dsRNAi molecules to knock down clock gene transcripts in a small intertidal crustacean, Eurydice pulchra, as well as our method for immunodetection of clock proteins in the brain. These metho...
Chapter
The clock neurons of the fruit fly Drosophila melanogaster have become a useful model for expressing misfolded protein aggregates that accumulate in several human neurodegenerative diseases. One advantage of such an approach is that the behavioral effects can be readily quantified on circadian locomotor rhythms, sleep or activity levels via automat...
Article
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Like many other insects in temperate regions, Drosophila melanogaster exploits the photoperiod shortening that occurs during the autumn as an important cue to trigger a seasonal response. Flies survive the winter by entering a state of reproductive arrest (diapause), which drives the relocation of resources from reproduction to survival. Here, we p...
Preprint
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Many animals use the Earth magnetic field (geoMF) for navigation. The favored mechanism for magnetosensitivity involves a blue-light (BL) activated electron transfer reaction between flavin adenine dinucleotide (FAD) and a chain of tryptophan (Trp) residues within the photoreceptor protein, CRYPTOCHROME (CRY). The spin-state of the resultant radica...
Article
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The courtship song of male Drosophila melanogaster is generated by wing vibration and contains an interpulse interval (IPI) which is species-specific and usually falls in the mean range of 30–40 ms. The IPI is extremely temperature-sensitive, so we wondered whether flies collected along the eastern coast of Australia between latitudes 16.9°S and 42...
Article
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The enzyme kynurenine 3-monooxygenase (KMO) operates at a critical branch-point in the kynurenine pathway (KP), the major route of tryptophan metabolism. As the KP has been implicated in the pathogenesis of several human diseases, KMO and other enzymes that control metabolic flux through the pathway are potential therapeutic targets for these disor...
Article
Background: Altered cellular vesicle trafficking has been linked to the pathogenesis of Huntington's disease (HD), a fatal, inherited neurodegenerative disorder caused by mutation of the huntingtin (HTT) protein. The Rab GTPase family of proteins plays a key role in regulation of vesicle trafficking, with distinct Rabs helping specify membrane ide...
Article
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In this paper, we review the role of the norpA-encoded phospholipase C in light and thermal entrainment of the circadian clock in Drosophila melanogaster. We extend our discussion to the role of norpA in the thermo-sensitive splicing of the per 3’ UTR, which has significant implications for seasonal adaptations of circadian behaviour. We use the no...
Article
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We have used the Cambridge Protein Trap resource (CPTI) to screen for flies whose locomotor rhythms are rhythmic in constant light (LL) as a means of identifying circadian photoreception genes. From the screen of ∼150 CPTI lines, we obtained seven hits, two of which targeted the glutamate pathway, Got1 (Glutamate oxaloacetate transaminase 1) and Gs...
Article
From 1980 to 1991, Kyriacou, Hall, and collaborators (K&H) reported that the Drosophila melanogaster courtship song has a 1-min cycle in the length of mean interpulse intervals (IPIs) that is modulated by circadian rhythm period mutations. In 2014, Stern failed to replicate these results using a fully automated method for detecting song pulses. Man...
Article
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Drosophila suzukii (Matsumara) also called Spotted Wing Drosophila (SWD), is an invasive pest species originally from Asia that has now spread widely across Europe and North America. The majority of drosophilids including the best known Drosophila melanogaster only breed on decaying fruits. On the contrary, the presence of a strong serrated oviposi...
Article
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DNA double-strand breaks are a feature of many acute and long-term neurological disorders, including neurodegeneration, following neurotrauma and after stroke. Persistent activation of the DNA damage response in response to double strand breaks contributes to neural dysfunction and pathology as it can force post-mitotic neurons to re-enter the cell...
Article
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With the approach of winter, many insects switch to an alternative protective developmental program called diapause. Drosophila melanogaster females overwinter as adults by inducing a reproductive arrest that is characterized by inhibition of ovarian development at previtellogenic stages. The insulin producing cells (IPCs) are key regulators of thi...
Conference Paper
Background Metabolic dysfunction is a hallmark of HD pathology. Decreased glucose metabolism and increased lactate concentrations in HD brains suggest mitochondrial involvement in the disease. Moreover, alterations in mitochondrial fission/fusion balance have also been reported in several HD models, with repercussions on the ability of cells to cle...
Data
Genetic crosses showing A) the lines carrying D. pseudoobscura-tim on chromosome II were crossed to the double balancers (P) to combine the transgenes with markers on chromosome III. B) The lines carrying D. pseudoobscura-per on chromosome III were crossed to the double balancers (P) to combine the transgenes with markers on chromosome II. C) The f...
Article
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The fruit fly Drosophila melanogaster survives thermally stressful conditions in a state of reproductive dormancy (diapause), manifested by reduced metabolic activity and arrested ovarian development in females. Unlike insects that rely primarily on photoperiodic stimuli to initiate the diapause program, in this species dormancy is regulated by low...
Article
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In response to adverse environmental conditions many organisms from nematodes to mammals deploy a dormancy strategy, causing states of developmental or reproductive arrest that enhance somatic maintenance and survival ability at the expense of growth or reproduction. Dormancy regulation has been studied in C. elegans and in several insects, but how...
Article
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The level of rescue of clock function in genetically arrhythmic Drosophila melanogaster hosts using interspecific clock gene transformation was used to study the putative intermolecular coevolution between interacting clock proteins. Among them PER and TIM are the two important negative regulators of the circadian clock feedback loop. We transforme...
Article
Unlike many insects where photoperiod per se induces diapause, reproductive arrest in Drosophila melanogaster adult females is observed at colder temperatures and can be enhanced by shorter photoperiods. Traditional experimental protocols raise flies at 25°C from the larval stage and then the adults are placed at 12°C for between 12 and 28 days. Af...
Article
The spread of adaptive genetic variants in populations is a cornerstone of evolutionary theory but with relatively few biologically well-understood examples. Previous work on the ls-tim variant of timeless, which encodes the light-sensitive circadian regulator in Drosophila melanogaster, suggests that it may have originated in southeastern Italy. F...
Article
Liang et al. (2017) demonstrate how neuropeptides from two groups of clock cells appear to be responsible for the fly’s circadian neurons becoming active at different times of day. By delaying the activity of their clock cell targets, they give rise to morning and evening behavior.
Article
Full-text available
Stern has criticized a body of work from several groups that have independently studied the so-called "Kyriacou and Hall" courtship song rhythms of maleDrosophila melanogaster,claiming that these ultradian ∼60-s cycles in the interpulse interval (IPI) are statistical artifacts that are not modulated by mutations at theperiod(per) locus [Stern DL (2...
Article
Full-text available
D. melanogaster enters a state of reproductive arrest when exposed to low temperatures (12°C) and shorter photoperiods. A number of studies have suggested that diapause has recently evolved in European D. melanogaster populations, that it is not present in the sibling species D. simulans, that it is non-photoperiodic in American D. melanogaster pop...
Article
Full-text available
Seasonal overwintering in insects represents an adaptation to stressful environments and in European Drosophila melanogaster females, low temperatures and short photoperiods can induce an ovarian diapause. Diapause may represent a recent (<15Ky) adaptation to the colonisation of temperate Europe by D. melanogaster from tropical sub-Saharan Africa,...
Article
Full-text available
Diapause is an actively induced dormancy that has evolved in Metazoa to resist environmental stresses. In temperate regions, many diapausing insects overwinter at low temperatures by blocking embryonic, larval or adult development. Despite its Afro-tropical origin, Drosophila melanogaster migrated to temperate regions of Asia and Europe where femal...
Data
Ovarian development in highly diapausing lines at 23°C is normal and comparable to controls. Females from all highly diapausing lines used throughout the experiments (Df(3L)dilp1-5/dilp2,3,5-; chicoKG00032; dilp2>hid,rpr; InsP3>hid,rpr; dilp2(p)>Ork1 and c929>sImp-L2) exposed for 11 days at 23°C exhibited normal gonadal maturation comparable to con...
Data
LD conditions, and cpoA347V, cpo SNP 48034 and tim genetic backgrounds considered throughout the experiments. (DOCX)
Data
Highly diapausing genotypes are all fertile. Females of high diapause strains dissected after 11 days at 23°C show no diapause. Flies were collected after 5 h post eclosion and exposed to 23°C LD12.12 for 11 days before dissection. (DOCX)
Article
Full-text available
couch potato (cpo) encodes an RNA binding protein that has been reported to be expressed in the peripheral and central nervous system of embryos, larvae and adults, including the major endocrine organ, the ring gland. A polymorphism in the D. melanogaster cpo gene coding region displays a latitudinal cline in frequency in North American populations...
Data
cpo48034(A/T) genotype frequencies against latitude. Panels A, B and C show how the SNP cpo48034(A/T) genotype frequencies (A/A, A/T and T/T respectively), change with latitude of collection. (JPG)
Data
Details of the flies used in the SNP cpo48034(A/T) study. N: number of alleles analysed. Lat: latitude in degrees North. Long: longitude in degrees (Negative values: West; Positive values: East). Alt: altitude in metres above sea level. The last column shows the results of the Hardy-Weinberg test. *: p<0.05. (DOCX)
Data
LD values calculated for each individual population and for the whole dataset. The analysis was carried out including the heterozygotes for both SNPs (DH, Double Heterozygotes), and excluding them from the dataset. When DH are included, observed frequency of each haplotype was estimated by the software, based on Maximum Likelihood The last row show...
Data
Details of the flies used in the cpoAla347Val study. N: number of alleles analysed. Lat: latitude in degrees North. Long: longitude in degrees (Negative values: West; Positive values: East). Alt: altitude in meters above sea level. The last column shows the results of the Hardy-Weinberg test. *: p<0.01; ***: p<0.001. (DOCX)
Data
cpo isoforms as of September 2008. Schematic representation of the six cpo splicing variants. Dark blue boxes encode the protein, whereas light blue ones represent the 5? and 3? UTR regions. The red and blue arrows represent the position of (then) SNP ?A356V? and SNP ?48034 (A/T)? respectively. The figure is not to scale and was redrawn from the da...
Data
Frequency of In(3R)Payne in a subset of the European populations. N: number of alleles analysed. f(st) frequency of standard arrangements. f(in) frequency of inverted chromosomes. CL: 95% confidence limits calculated with the Wilson/Brown method. (DOCX)
Data
Results of 4-way ANOVAs on diapause. LD: experimental samples. DD: controls. Significant values are indicated in red. (DOCX)
Data
cpoA347V genotype frequencies against latitude. Panels A, B and C show how cpoAla347Val genotype frequencies (C/C, T/C, T/T respectively), change with latitude of collection. *: p<0.05. (JPG)
Data
Diapause incidence in the Treviso population (TOT) and in the four sublines (sTA, sTT, sCA and sCT) under constant darkness (DD). Y axis: percentage of diapause in two replicates per population (1 and 2). A) Diapause in LD 8:16. The two time points are compared (12 and 28 days, dotted and plain bars respectively). B) Diapause in 16:8, comparison be...
Article
Full-text available
Background The kynurenine pathway (KP), the major catabolic route of tryptophan (TRP) metabolism, has been closely linked to the pathogenesis of several brain disorders. This pathway produces several neuroactive metabolites, including 3-hydroxykynurenine (3-HK), quinolinic acid (QUIN) and kynurenic acid (KYNA). A shift towards the synthesis of neur...
Article
Full-text available
Metabolites of the kynurenine pathway (KP) of tryptophan (TRP) degradation have been closely linked to the pathogenesis of several neurodegenerative disorders. Recent work has highlighted the therapeutic potential of inhibiting two critical regulatory enzymes in this pathway-kynurenine-3-monooxygenase (KMO) and tryptophan-2,3-dioxygenase (TDO). Muc...
Article
Full-text available
Background: The environmental light-dark cycle is the dominant cue that maintains 24-h biological rhythms in multicellular organisms. In Drosophila, light entrainment is mediated by the photosensitive protein CRYPTOCHROME, but the role and extent of transcription regulation in light resetting of the dipteran clock is yet unknown. Given the broad t...
Article
Under standard laboratory conditions of rectangular light/dark cycles and constant warm temperature, Drosophila melanogaster show bursts of morning (M) and evening (E) locomotor activity and a "siesta" in the middle of the day. These M and E components have been critical for developing the neuronal dual oscillator model in which clock gene expressi...
Article
Full-text available
Previous analysis of Drosophila circadian behavior under natural conditions has revealed a number of novel and unexpected features. Here we focus on the oscillations of per and tim mRNAs and their posttranscriptional regulation and observe significant differences in molecular cycling under laboratory and natural conditions. In particular, robust pe...
Article
Full-text available
The circadian clock provides the temporal framework for rhythmic behavioral and metabolic functions. In the modern era of industrialization, work, and social pressures, clock function is jeopardized, and can result in adverse and chronic effects on health. Understanding circadian clock function, particularly individual variation in diurnal phase pr...
Article
Full-text available
In contrast to the well mapped molecular orchestration of circadian timekeeping in terrestrial organisms, the mechanisms that direct tidal and lunar rhythms in marine species are entirely unknown. Using a combination of biochemical and molecular approaches we have identified a series of metabolic markers of the tidal clock of the intertidal isopod...
Article
Full-text available
The study of circadian behavior in model organisms is almost exclusively confined to the laboratory, where rhythmic phenotypes are studied under highly simplified conditions such as constant darkness or rectangular light-dark cycles. Environmental cycles in nature are far more complex, and recent work in rodents and flies has revealed that when pla...
Chapter
33.1 Introduction 557 33.2 Modeling HD in Yeast 558 33.2.1 Yeast as a Model Organism 558 33.2.2 Developing Yeast Models of HD 559 33.2.3 Characterization of Yeast Models of HD 560 33.2.4 Using Yeast to Identify Genetic and Chemical Modifiers of HD 561 33.3 Modeling HD in C. elegans 562 33.3.1 C. elegans as a Model Organism 562 33.3.2 Development, C...
Article
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Highlights • Lutzomyia longipalpis in Brazil has recently undergone complex speciation events. • Anopheles cruzii in southern Brazil has also undergone recent speciation. • The circadian clock mechanisms of both sandflies and mosquitoes have been described.
Article
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The blue-light sensitive photoreceptor cryptochrome (CRY) may act as a magneto-receptor through formation of radical pairs involving a triad of tryptophans. Previous genetic analyses of behavioral responses of Drosophila to electromagnetic fields using conditioning, circadian and geotaxis assays have lent some support to the radical pair model (RPM...
Article
Full-text available
A central pathological hallmark of Parkinson's disease (PD) is the presence of proteinaceous depositions known as Lewy bodies, which consist largely of the protein α-synuclein (aSyn). Mutations, multiplications and polymorphisms in the gene encoding aSyn are associated with familial forms of PD and susceptibility to idiopathic PD. Alterations in aS...
Article
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Background In the fruit fly Drosophila melanogaster, interlocked negative transcription/translation feedback loops provide the core of the circadian clock that generates rhythmic phenotypes. Although the current molecular model portrays the oscillator as cell autonomous, cross-talk among clock neurons is essential for robust cycling behavior. Never...
Article
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Author Summary The circadian clock consists of an extensive genetic network that drives daily rhythms of physiological, biochemical and behavioural processes. The network is evolutionary conserved and has been extensively studied in a broad range of organisms. Another genetic network constitutes the photoperiodic clock and monitors the seasonal cha...
Article
Full-text available
Many higher animals have evolved the ability to use the Earth's magnetic field, particularly for orientation. Drosophila melanogaster also respond to electromagnetic fields (EMFs), although the reported effects are quite modest. Here we report that negative geotaxis in flies, scored as climbing, is disrupted by a static EMF, and this is mediated by...
Article
Full-text available
Genetic variations in circadian clock genes may serve as molecular adaptations, allowing populations to adapt to local environments. Here, we carried out a survey of genetic variation in Drosophila cryptochrome (cry), the fly's dedicated circadian photoreceptor. An initial screen of 10 European cry alleles revealed substantial variation, including...
Article
Full-text available
Organisms from bacteria to humans have evolved under predictable daily environmental cycles owing to the Earth's rotation. This strong selection pressure has generated endogenous circadian clocks that regulate many aspects of behaviour, physiology and metabolism, anticipating and synchronising internal time-keeping to changes in the cyclical enviro...
Article
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Humans sleep approximately a third of their lifetime. The observation that individuals with either long or short sleep duration show associations with metabolic syndrome and psychiatric disorders suggests that the length of sleep is adaptive. Although sleep duration can be influenced by photoperiod (season) and phase of entrainment (chronotype), hu...
Article
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Tidal (12.4 hr) cycles of behavior and physiology adapt intertidal organisms to temporally complex coastal environments, yet their underlying mechanism is unknown. However, the very existence of an independent "circatidal" clock has been disputed, and it has been argued that tidal rhythms arise as a submultiple of a circadian clock, operating in du...