Urs Albrecht
urs.albrecht@unifr.ch
+41 26 300 8636
https://orcid.org/0000-0002-0663-8676
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Ordentliche_r Professor_in,
Departement für Biologie
PER 09 bu. 1.107N
Ch. du Musée 5
1700 Fribourg
Forschung und Publikationen
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Publications
126 Publikationen
Mutational scanning of the CLOCKΔ19 domain identifies amino acids modulating circadian clock dynamics and co‐regulator binding
Acta Physiologica (2022) | ArtikelPhysical Interaction between Cyclin-Dependent Kinase 5 (CDK5) and Clock Factors Affects the Circadian Rhythmicity in Peripheral Oscillators
Clocks & Sleep (2022) | ArtikelCDK5 influences the organization of the Circadian Machinery in peripheral clocks
Juergen Alexander RIPPERGER and Urs Albrecht and Andrea Brenna , Cold Spring Harbor Laboratory (2021) | SonstigesLight affects behavioral despair involving the clock gene Period 1
PLOS Genetics (2021) | ArtikelDeletion of the Clock GenePeriod2 (Per2)in Glial Cells Alters Mood-Related Behavior in Mice
Tomaz Martini, Jürgen A. Ripperger, Jimmy Stalin, Andrej Kores, Michael Stumpe, Urs Albrecht, (2020) | PreprintLight affects behavioral despair involving the clock genePeriod 1
Iwona Olejniczak, Jürgen A. Ripperger, Federica Sandrelli, Anna Schnell, Laureen Mansencal-Strittmatter, Ka Yi Hui, Andrea Brenna, Naila Ben Fredj, Urs Albrecht, (2020) | PreprintCyclin-dependent kinase 5 (CDK5) regulates the circadian clock
eLife (2019) | ArtikelCyclin Dependent Kinase 5 (CDK5) Regulates the Circadian Clock
Andrea Brenna and Iwona Olejniczak and Rohit Chavan and Juergen A Ripperger and Sonja Langmesser and Elisabetta Cameroni and Zehan Hu and Claudio De Virgilio and Joern Dengjel and Urs Albrecht , Cold Spring Harbor Laboratory (2019) | SonstigesMeasuring Food Anticipation in Mice
Clocks & Sleep (2018) | Artikelβ-Klotho deficiency protects against obesity through a crosstalk between liver, microbiota, and brown adipose tissue
JCI Insight (2017) | Artikel -
Forschungsprojekte
Mouse metabolic phenotyping platform for UNIFR
Status: AbgeschlossenBeginn 01.12.2021 Ende 30.11.2022 Finanzierung SNF Projektblatt öffnen 5 co-applicants and I are submitting a request for 283,000 CHF to purchase a mouse metabolic phenotyping system with a body composition magnetic resonance imaging unit. These units, that will be run as a pay-per-use platform service within the Faculty of Science and Medicine at the University of Fribourg, are critically important to multiple different avenues of ongoing research. Obtaining high resolution metabolic, behavioral, and body composition data is crucial to the projects outlined in the proposal and will be of great scientific value to any group using mice as model organisms within the University. The scientific domains directly involved in this proposal are varied and include obesity, cancer, circadian rhythm, aging, hypoxia, and pharmacology research. The specific necessity for obtaining these machines is outlined for each project but the more general need for such machines is to increase the scientific value of every lab mouse used, a very important goal for all research institutions in Switzerland. Environmental conditions, clock and sleep
Status: AbgeschlossenBeginn 01.04.2019 Ende 31.03.2023 Finanzierung SNF Projektblatt öffnen The earth’s rotation around its axis causes periodic exposure of animals and humans to sunlight. This daily recurring event has been internalized in most organisms in the form of a circadian clock mechanism, which is at the cellular level an autoregulatory transcriptional-translational feedback loop with a period of about 24 hours. In order to stay in tune with the seasonal light changes, the clock needs to be able to adapt to such changes. This is one of the reasons why we can adapt to jet-lag and shift work. Epidemiological studies indicate that defects in the clock mechanism and its adaptability to such changes contribute most likely to metabolic and neurological diseases, which are associated with sleep problems. In this proposal we are studying how environmental challenges modulate the clock and sleep. We focus on the mouse Period (Per) genes, because they are core clock components and also components of the clock input pathway. The first part investigates the regulation of phosphorylation of PER proteins in response to environmental challenge. The second part aims to unravel the role of neurons and astrocytes, which both express Per genes, in coordinating responses to environmental changes. The third part aims at understanding what role Per genes in astrocytes and neurons play in the regulation of sleep. Adaptation of the circadian clock to changes in the environment
Status: AbgeschlossenBeginn 01.04.2016 Ende 31.03.2019 Finanzierung SNF Projektblatt öffnen Mammals experience environmental changes at various time scales, including daily light dark alterations and seasonal variations. In order to optimize the organism’s performance a mechanism developed to predict daily recurring events. This mechanism is termed circadian clock, which is at the cellular level an auto-regulatory feedback loop that cycles in a 24-hour rhythm. However, this mechanism has to be adaptable to changes, because daily light-dark transitions vary over the year. Defects in clock components as well as in clock adaptability to environmental challenges contribute most likely to metabolic and neurological diseases. In this proposal we are investigating how environmental challenges modulate the clock with a focus on the Per2 gene, which is a common component of both the clock input pathways and the core clock mechanism. The first part of the project focuses on the health benefits when day-length matches with clock period in mice. The second part investigates the regulation of phosphorylation of the PER2 protein a target of various protein kinases, which act on the PER2 protein in response to environmental challenges. The third part aims at understanding how neurons and astrocytes, which both express PER2, coordinate their influence to modulate responses to environmental challenges. Microchip-based flow cell sorting in biomedicine and material sciences
Status: AbgeschlossenBeginn 01.05.2015 Ende 30.04.2016 Finanzierung SNF Projektblatt öffnen Microchip-based flow cell sorting in biomedicine and material sciences Clock synchronization: From brain to periphery or periphery to brain?
Status: AbgeschlossenBeginn 01.04.2013 Ende 31.03.2016 Finanzierung SNF Projektblatt öffnen Clock synchronization: From brain to periphery or periphery to brain? Fluorescence-Mediated Tomography (FMT) to study cellular and molecular events in physiology and pathology: application to cancer, cardiovascular and circadian biology
Status: AbgeschlossenBeginn 01.02.2011 Ende 31.01.2012 Finanzierung SNF Projektblatt öffnen Fluorescence-Mediated Tomography (FMT) to study cellular and molecular events in physiology and pathology: application to cancer, cardiovascular and circadian biology Adaptation mechanisms of the circadian clock to light and temperature
Status: AbgeschlossenBeginn 01.04.2010 Ende 31.03.2013 Finanzierung SNF Projektblatt öffnen Life on earth uses the sun as a reference point to time biological processes over the 24 hours of a day. To optimize energy expenditure and uptake a mechanism developed internalizing the cyclic availability of light in the form of the circadian clock. Because the period length of one cycle is circadian (circa diem = about one day) and not exactly 24 hours, the clock needs to be adapted periodically to serve as a reliable predictor of solar time. In this proposal we are interested in adaptation mechanisms of the mammalian circadian clock to changing light and temperature conditions. The Circadian Clock and Mood Disorders: from Animal Models to Human Disease
Status: AbgeschlossenFlow cytometry opens new avenues for cell-based analyses in biomedical research
Status: AbgeschlossenBeginn 01.08.2007 Ende 31.07.2008 Finanzierung SNF Projektblatt öffnen This research proposal requests funding for the acquisition of a flow cytometer equipped with a temperature-controlled autosampler. Such an instrument allows a quantitative readout from a variety of fluorescent cell-based assay systems, which are being used, for example, to analyze cell cycle progression, to monitor apoptosis to quantify lipid transport, and to analyze cell surface expression of marker proteins. In combination with an autosampler, the instrument is suited for high-throughput screens, which have now become extremely successful for gene discovery in organisms for which deletion libraries or siRNA collections are available, such as yeast, C. elegans, T. brucei, and mammalian cells. There is presently no flow cytometer or equivalent instrument available at our campus. The instrument would thus allow us to perform experiments that are currently either not possible, or require much more time and reagents than a corresponding readout based on flow cytometry. The four SNF-funded research groups applying for this grant will be the main users of this instrument, but additional groups have already expressed their interest in using this equipment. The four groups will employ the instrument to study (i) lipid homeostasis in yeast, (ii) the connection between the circadian clock and aging, (iii) the coordination between mitochondrial biogenesis and the cell cycle in the parasitic protozoan, Trypanosoma brucei, and (iv) the role of adipose tissues of different origins in obesity-associated vascular dysfunctions. As is evident from this list of topics, the requested instrument is extremely versatile and thus will serve the needs and will be open to the more than 25 research groups in the Life Sciences that are located on the campus. This flow cytometer would thus well complement more qualitative readouts that are presently typically performed by fluorescent microscopy. Adaptation mechanisms of the circadian clock to light and temperature
Status: AbgeschlossenBeginn 01.04.2007 Ende 31.03.2010 Finanzierung SNF Projektblatt öffnen Life on earth has used the sun as a reference point to time biological processes over the 24 hours of a day. To optimize energy expenditure and uptake a mechanism developed internalizing the cyclic availability of light in the form of the circadian clock. Because the period length of one cycle is circadian (circa diem = about one day) and not exactly 24 hours, the clock needs to be reset periodically to serve as a reliable predictor of solar time. The light resetting signal is mediated via the eye through the retinohypothalamic tract (RHT) to the suprachiasmatic nuclei (SCN), the central pacemaker of the circadian system located in the ventral hypothalamus. In this proposal we are interested in the mechanism that resets the clock in response to light. Specifically, the relationship between the Per2 and Rev-erba genes in this mechanism is studied. In a second project we are interested how the clock influences adaptation to low temperature via regulation of mitochondrial function. Working hypothesis: 1) Several signal transduction pathways seem to be involved in clock resetting. A regulated combinatorial activation of signaling pathways determines magnitude and direction of the phase shift to adjust the clock. 2) Adaptation to low temperature in animals is critically dependent on mitochondrial function, which is probably modulated by clock genes. Experimental design/methods: A) Microarray analysis using Affimetrix chips will be used, followed by verification using PCR and in situ hybridization methods. Candidate genes will be tested in an in vitro cell culture assay using RNAi and a lumicycle apparatus. Behavioral wheel-running tests will be used to study resetting in mice B) Behavioral experiments accompanied by biochemical analysis and cell culture experiments will be used to study the influence of the clock on mitochondrial function. Expected value of the proposed project: Understanding adaptation to changes in lighting and temperature conditions provides a framework for treatment of shift-work and jet-lag associated problems, such as depression and sleep loss. Understanding malfunctioning of energy metabolism due to lack of synchronization by the clock will provide insights to develop treatments to fight obesity and cancer. EUCLOCK: Entrainment of the circadian clock
Status: AbgeschlossenBeginn 01.01.2006 Ende 30.06.2011 Finanzierung Europa Projektblatt öffnen The circadian clock is a basic biological process that enables organisms to anticipate daily environmental changes by adjusting behavior, physiology and gene regulation. It impacts health and quality of life in regulating sleep and well-being, in the consequences of shift-work, in medical diagnosis/therapy, and in age-related changes. A critical feature of the clock is its synchronization to the external day (entrainment). Entrainment is the key to understanding the circadian clock and its control mechanisms. In EUCLOCK, highly competitive European researchers join forces to investigate the circadian clock under entrainment using the most advanced methods of functional genomics and phenomics comparing powerful genetic model organisms (humans, mice, flies, and yeast). Its four major innovations will shape the future of circadian research: - To compare genomic and phenomic aspects of the clock, SOPs will be developed for the first time that mimic aspects of the natural day (dawn/dusk, day-lengths, etc). - Protocols, devices and algorithms will be developed, enabling for the first time large-scale, non-invasive research on human entrainment in the field. - Developing the first animal models for shift-work, making animals 'work' and feed out of phase with their natural rhythms. The ensuing 'dys-entrainment' will be investigated at all levels, aiming to provide the insights needed to treat the symptoms and consequences of human shift-work. - Building on genome sequences, new genetic components and interactions will be identified that control the circadian clock and its entrainment. For the first time the experimental advantages of yeast will be extensively used. The tractability of yeast permits integration and reconstruction of elements and interactions gleaned from other systems. Together, these approaches allow systems biology research on circadian timing to be performed and integrated at the level of the genome, the proteome, and the metabolome. Molekulare und funktionelle Synchronisation der inneren Uhr durch Nahrung
Status: AbgeschlossenBeginn 01.01.2005 Ende 31.12.2006 Finanzierung Andere Circadiane Rhythmen sind von grundlegender Bedeutung in der Biologie. Sie garantieren die zeitliche Organisation und Funktion der Physiologie und des Verhaltens aber auch die Synchronisation biologischer Funktionen im Organismus während eines Tages. Eine Störung der circadianen Rhythmen kann im Menschen zu gesundheitlichen Problemen führen wie z.B. zu kardiovaskulären Problemen, Schlafstörungen, Depressionen und Krebs. Eine circadiane Uhr wurde zuerst in den suprachiasmatischen nuclei (SCN) gefunden. Ein entfernen dieser hypothalamischen nuclei führt im Hamster zu einer desorganisation vieler physiologischer Funktionen. Damit die Uhr im SCN verlässlich ist muss sie täglich dem licht-dunkel Wechsel angepasst werden. Die Tageslänge (Lichtdauer) wird dann vom SCN an die restlichen Organe des Körpers weitervermittelt. Interessanterweise haben die Zellen der verschiedenen Organe auch eine innere Uhr die in ihrem molekularen Aufbau der Uhr in den SCN Neuronen identisch ist. Diese sogenannt peripheren Uhren können nicht nur über den SCN koordiniert werden sondern sie können auch direkt über die Verfügbarkeit der Nahrung beeinflusst werden. Diese peripheren Uhren können sich zum Nahrungsangebot synchronisieren auch wenn die Uhr im SCN des Hirns defekt ist. Deshalb ist es von grossem Interesse Aufschluss über den Mechanismus zu finden welcher diese peripheren Uhren über den Metabolismus von Nahrung synchronisiert. Das Ziel dieses Projektes ist es diese Mechanismen auf molekularem Niveau zu charakterisieiren und neuroanatomische Marker der nahrungssynchronisierten Uhr zu identifizieren. Dieses Projekt wird Aufschluss darüber geben welche Funktionen die Uhrengene Per1 und Per2 in der Synchronisation der inneren Uhren zum Nahrungsangebot haben. EUCLOCK: Entrainment of the circadian clock
Status: AbgeschlossenDie innere Uhr, transkriptionnelle Regulation und Altern
Status: AbgeschlossenBeginn 01.04.2004 Ende 31.03.2007 Finanzierung SNF Projektblatt öffnen The circadian timing system provides a temporal structure across an organism to modulate and synchronize biological function. Individual cells contain the molecular set up to drive a circadian clock. All these individually ticking clocks are synchronized by a pacemaker that can be compared to an orchestras conductor. Disruption of the temporal programming and synchronization of the cellular clocks leads to changes in physiology and behavior, as observed in shift workers, jet lag and aging. In this proposal we are interested in the regulation of cellular events by the clock. Specifically, the relationship between Per genes, which are clock components, and the metabolism of radicals and transcriptional regulation of clock controlled genes are studied. The influence of light on the circadian clock of mice and men
Status: AbgeschlossenUnwinding the mammalian circadian clock - input pathways, central oscillator, and output signals
Status: AbgeschlossenBRAINTIME: The biological clock in the brain : circadian genes and the sense of time (BRAINTIME)
Status: AbgeschlossenBeginn 01.10.2002 Ende 30.09.2005 Finanzierung Europa Projektblatt öffnen Human adaptation to modern 24-h society is constrained by dominant endogenous periodicities in physiology and behaviour. These rhythms, including the sleep-wake cycle, are generated in the brain's suprachiasmatic nuclei (SCN). Their understanding has major biomedical impact in the combat of sleep disorders, control of fatigue and risk, adjustment to shift work, timing of drug therapies. Big strides are being made in unravelling the physiological and molecular basis of circadian rhythms. Building on these advances we combine molecular, brain and behaviour studies to elucidate the control of sleep-wakefulness in mouse models and humans. Human studies focus on screening for phase variations in sleep-wake rhythms and their molecular characterization. Mouse strains with genetically modified circadian genes are exploited to characterize the mechanism underlying SCN oscillations and establish time-specific neuroanatomical mapping of circadian gene expression throughout the brain. Complementary expertise allows the assembly of a coherent picture of generation and synchronization of neuronal clocks involved in adaptation to a rotating planet. The relationship between the circadian clock and the mesolimbic dopaminergic signaling system
Status: AbgeschlossenThe circadian clock and ageing
Status: AbgeschlossenBeginn 01.02.2002 Ende 01.02.2003 Finanzierung Andere Projektblatt öffnen The fidelity of DNA replication and the ability of controlling reactive oxygen species (ROS) are important determinants of ageing. They are coordinated in an intricate manner in the cell. Candidate genes that could be involved in the control of DNA replication and metabolism of ROS have been identified in a subtractive hybridization screen in which target genes of the circadian clock gene Per2 have been searched for. Preliminary results indicate a difference in ageing between wild type and Per2 mutant mice as manifested by an age related change in fur colour. We hypothesize that the circadian clock intersects on the cellular level with DNA replication and/or removal of free oxygen radicals. We will test our hypothesis by challenging wild type and Per2 mutant mice, in which the circadian clock is defective, with agents known to accelerate ageing. Genes that are downregulated in Per2 mutant mice will be studied in relation to the aging process. Overexpression of these genes is planed in Per2 mutant cells and a rescue of ageing is expected. Genetic interaction of Per and Cry genes
Status: AbgeschlossenBeginn 01.01.2002 Ende 01.01.2003 Finanzierung Andere Most organisms form bacteria to humans have an internal clock that enables them to predict daily events. In mammals the center of the circadian clock is located in the ventral part of the hypothalamus the so called suprachiasmatic nuceli (SCN). We and others found central molecular components of the mammalian clock, such as the Period genes (Per1, Per2, Per3) and the Cryptochrome genes (Cry1, Cry2). The aim of this proposal is to elucidate the specific roles for the Per and the Cry genes in the clock mechanism by generating mice mutant in Per and Cry genes (e.g. Per1/Cry1; Per1/Cry2; Per2/Cry1 etc.). A better understanding of the molecular bases of the circadian clock will give us key insights for treatment of diseases that have their roots in the circadian system, such as Jet-lag, Advanced and Delayed Sleep-Phase Syndromes and depression. Interaction of Per and Cry Genes in the Mammalian Circadian Clock
Status: AbgeschlossenCircadian rhythms: from genes to behavior
Status: AbgeschlossenBeginn 01.04.2001 Ende 31.03.2004 Finanzierung SNF Projektblatt öffnen Temporal organization is a fundamental feature of all living organisms and is essential for survival and behavior. The presence of a biological clock enables an organism to predict daily events such as sunrise, even in the absence of a day/night cycle. This autonomous cycle of sleep and wakefulness is approximately 24 hours, or circadian. The mammalian circadian clock resides in the ventral part of the hypothalamus, which has a major role in producing responses to emotional and environmental changes. Mice mutant in clock genes show behavioral disorders that are observed in patients with sleep disturbances and certain forms of depression. Therefore mice mutant in Per2, which is a central gene of the clock, provide a unique opportunity to study human behavioral problems. In this proposal we want to identify Per2 dependent genes that are transducing circadian changes to the physiology of the organism. The findings will lead to an understanding of disorders, such as depression, that have their roots in the circadian system. Altered Glutamatergic Signaling in mPer2 mutant mice
Status: Abgeschlossen