A5066125615- Circadian rhythm and melatonin
- Asthma and respiratory diseases
- Light effects on plants
- Epigenetics and DNA Methylation
- Milk Quality and Mastitis in Dairy Cows
- Dietary Effects on Health
- Genetic and phenotypic traits in livestock
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Immune Cell Function and Interaction
- Immune cells in cancer
- Photoreceptor and optogenetics research
- Spaceflight effects on biology
- Microbial infections and disease research
- Effects of Environmental Stressors on Livestock
- Animal health and immunology
- Systemic Sclerosis and Related Diseases
- Allergic Rhinitis and Sensitization
- Reproductive Physiology in Livestock
- Estrogen and related hormone effects
- T-cell and B-cell Immunology
- Digestive system and related health
- Neuroendocrine regulation and behavior
- Agriculture, Water, and Health
- Neonatal Respiratory Health Research
Manchester University NHS Foundation Trust
2024
St Mary's Hospital
2024
St. Mary's Hospital
2024
University of Manchester
2014-2023
Manchester Academic Health Science Centre
2018-2021
Teagasc - The Irish Agriculture and Food Development Authority
2009-2012
University College Dublin
2009
Recent studies reveal that airway epithelial cells are critical pulmonary circadian pacemaker cells, mediating rhythmic inflammatory responses. Using mouse models, we now identify the repressor REV-ERBα as essential to mechanism coupling clock innate immunity, involving both myeloid and bronchial in temporal gating determining amplitude of response inhaled endotoxin. Dual mutation its paralog REV-ERBβ epithelia further augmented responses chemokine activation, but also initiated a basal...
The circadian clock regulates many aspects of immunity. Bacterial infections are affected by time day, but the mechanisms involved remain undefined. Here we show that loss core protein BMAL1 in macrophages confers protection against pneumococcal pneumonia. Infected mice both reduced weight and lower bacterial burden circulating blood. In vivo studies macrophage phagocytosis reveal increased ingestion following Bmal1 deletion, which was also seen vitro. BMAL1-/- exhibited marked differences...
The glucocorticoid receptor (GR) is a major drug target in inflammatory disease. However, chronic (GC) treatment leads to disordered energy metabolism, including increased weight gain, adiposity, and hepatosteatosis - all programs modulated by the circadian clock. We demonstrated that while antiinflammatory GC actions were maintained irrespective of dosing time, liver was significantly more sensitive during day. Temporal segregation action underpinned physical interaction GR with...
Pulmonary inflammatory responses lie under circadian control; however, the importance of mechanisms in underlying fibrotic phenotype is not understood. Here, we identify a striking change to these resulting gain amplitude and lack synchrony within pulmonary tissue. These changes result from an infiltration mesenchymal cells, important cell type pathogenesis fibrosis. Mutation core clock protein REVERBα cells exacerbated development bleomycin-induced fibrosis, whereas mutation club or myeloid...
Resistance to the intestinal parasitic helminth Trichuris muris requires T-helper 2 (TH2) cellular and associated IgG1 responses, with expulsion typically taking up 4 weeks in mice. Here, we show that time-of-day of initial infection affects efficiency worm expulsion, strong TH2 bias early morning-infected Conversely, mice infected at start night delayed resistance infection, this is feeding-driven metabolic cues, such feeding restriction day-time normally nocturnal-feeding disrupts...
The annual photoperiod cycle provides the critical environmental cue synchronizing rhythms of life in seasonal habitats. In 1936, Bünning proposed a circadian-based coincidence timer for photoperiodic synchronization plants. Formal studies support universality this so-called timer, but we lack understanding mechanisms involved. Here show mammals that long photoperiods induce circadian transcription factor BMAL2, pars tuberalis pituitary, and triggers summer biology through eyes...
The mammalian circadian clock exerts control of daily gene expression through cycles DNA binding. Here, we develop a quantitative model how finite pool BMAL1 protein can regulate thousands target sites over time scales. We used imaging to track dynamic changes in endogenous labelled proteins across peripheral tissues and the SCN. determine contribution multiple rhythmic processes coordinating binding, including cycling molecular abundance, binding affinities, repression. find nuclear...
Pulmonary airway epithelial cells (AECs) form a critical interface between host and environment. We investigated the role of circadian clock using mice bearing targeted deletion gene brain muscle ARNT-like 1 (
ABSTRACT The circadian clock is a critical regulator of immune function. We recently highlighted role for the in mouse model pulmonary inflammation. epithelial protein Bmal1 was required to regulate neutrophil recruitment response inflammatory challenge. regulated glucocorticoid receptor (GR) chemokine, CXC chemokine ligand 5 (CXCL5), providing candidate mechanism. now show that control neutrophilia persists without rhythmic availability. Epithelial GR‐null mice had elevated expression...
Background Asthma is an inflammatory disease of the airway showing a strong time day rhythm. Airway hyperresponsiveness dominant feature asthma, but it not known if this under clock control. The circadian powerfully regulates inflammation. protein REV-ERBα to play key role as repressor response. Objectives To determine allergy mediated gated by protein, REV-ERBα. Methods After exposure intra-nasal house dust mite allergen challenge model at either dawn or dusk, hyper-responsiveness...
Robust inflammatory responses are critical to survival following respiratory infection, with current attention focused on the clinical consequences of Coronavirus pandemic. Epigenetic factors increasingly recognized as important determinants immune responses, and EZH2 is a prominent target due availability highly specific efficacious antagonists. However, very little known about role in myeloid lineage. Here, we show acts macrophages limit activation, neutrophils for chemotaxis. Selective...
Abstract The circadian clock controls the physiological function of tissues through regulation thousands genes in a cell‐type‐specific manner. core cellular is transcription–translation negative feedback loop, which can recruit epigenetic regulators to facilitate temporal control gene expression. Histone methyltransferase, mixed lineage leukemia 3 (MLL3) was reported be required for maintenance oscillations cultured cells. Here, we test role MLL3 organization whole animals. Using mice...
Data were available from 1657 heifers across 48 dairy farms which visited once, on average 9 days (± 5.2) prior to the mating start date (23 April, ± 12.6). Blood samples collected via coccygeal venepuncture for progesterone (P4) analysis, and animals scanned presence or absence of corpora lutea (CL), determine luteal status. A comparison status between ultrasound (CL identified) P4 (≥ 1 ng/ml), based a single measurement point, showed poor agreement (K = 0.32). The majority classified as...
<h3>Introduction and Objectives</h3> Asthma exhibits diurnal variation, with symptoms worsening at night, coincident increased airway inflammation narrowing overnight. Our research has highlighted the role of molecular clock in regulating hyperresponsiveness (AHR), a critical feature asthma. This study aims to investigate how epithelial regulates AHR variation. <h3>Methods</h3> We used Cre-lox system generate mice specific deletion <i>Rev-erbα</i> CCSP-expressing cells...
ORAL ABSTRACT SESSION 1—Asthma: from mechanisms to managementO01 Serum IL-1RL1-A levels predict an eosinophilic subtype of asthma in preschool wheezing childrenM. E. Ketelaar1, K. Van De Kant2, F. N. Dijk1, M. Klaassen3, Grotenboer4, C. Nawijn4, Dompeling2, G. H. Koppelman1 1University Medical Center Groningen, Beatrix Children's Hospital, Groningen Research Institute for Asthma and COPD (GRIAC), The Netherlands; 2Department Pediatric Pulmonology, School Public Health Primary Care (CAPHRI),...
Abstract The mammalian circadian clock exerts substantial control of daily gene expression through cycles DNA binding. Understanding mechanisms driving the is hampered by lack quantitative data, without which predictive mathematical models cannot be developed. Here we develop a understanding how finite pool BMAL1 protein can regulate thousands target sites over time scales. We have used fluorescent correlation spectroscopy (FCS) to track dynamic changes in CRISPR-modified fluorophore-tagged...
Abstract Pulmonary inflammatory responses lie under circadian control; however the importance of mechanisms in fibrosis is not understood. Here, we identify a striking change to these resulting gain amplitude and lack synchrony within pulmonary fibrotic tissue. These changes result from an infiltration mesenchymal cells, important cell type pathogenesis fibrosis. Mutation core clock protein REVERBα cells exacerbated development bleomycin-induced fibrosis, whereas mutation club or myeloid had...
Abstract The annual photoperiod cycle provides the critical environmental cue synchronizing rhythms of life in seasonal habitats. In 1936, Bünning proposed a circadian-based coincidence timer for photoperiodic synchronization plants. Formal studies support universality this so-called timer, but we lack understanding mechanisms involved. Here show mammals that long photoperiods induce circadian transcription factor BMAL2 , pars tuberalis pituitary, and triggers summer biology through eyes...