Jacob G Holland, Aidan J O'Donnell, Alejandra Herbert-Mainero, Sarah E Reece
{"title":"Phenotypic and fitness consequences of plasticity in the rhythmic replication of malaria parasites.","authors":"Jacob G Holland, Aidan J O'Donnell, Alejandra Herbert-Mainero, Sarah E Reece","doi":"10.1098/rstb.2023.0340","DOIUrl":"10.1098/rstb.2023.0340","url":null,"abstract":"<p><p>The environments that parasites experience within hosts change dramatically over 24 h. How rhythms shape host-parasite-vector interactions is poorly understood owing to the challenges of disentangling the roles of rhythms of multiple interacting species in the context of the complex lifecycles of parasites. Using canonical circadian clock-disrupted hosts, we probe the limits of flexibility in the rhythmic replication of malaria (<i>Plasmodium</i>) parasites and quantify the consequences for fitness proxies of both parasite and host. We reveal that parasites alter the duration of their replication rhythm to resonate with host rhythms that have short (21 h) daily T-cycles as accurately as when infecting hosts with 24 h cycles, but appear less capable of extending their replication rhythm in hosts with long (27 h) cycles. Despite matching the period of short T-cycle hosts, parasites are unable to lock to the correct phase, likely leading to lower within-host productivity and a reduction in transmission potential. However, parasites in long T-cycle hosts do not experience substantial fitness costs. Furthermore, T-cycle duration does not affect disease severity in clock-disrupted hosts. Understanding the rhythmic replication of malaria parasites offers the opportunity to interfere with parasite timing to improve health and reduce transmission.This article is part of the Theo Murphy meeting issue issue 'Circadian rhythms in infection and immunity'.</p>","PeriodicalId":19872,"journal":{"name":"Philosophical Transactions of the Royal Society B: Biological Sciences","volume":"380 1918","pages":"20230340"},"PeriodicalIF":5.4,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11753878/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143024291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hannah Rees, Nina M Rzechorzek, Rebecca B Hughes, Antony N Dodd, James J L Hodge, Tyler J Stevenson, Malcolm von Schantz, Robert J Lucas, Sarah E Reece, Charalambos P Kyriacou, Andrew J Millar
{"title":"BioClocks UK: driving robust cycles of discovery to impact.","authors":"Hannah Rees, Nina M Rzechorzek, Rebecca B Hughes, Antony N Dodd, James J L Hodge, Tyler J Stevenson, Malcolm von Schantz, Robert J Lucas, Sarah E Reece, Charalambos P Kyriacou, Andrew J Millar","doi":"10.1098/rstb.2023.0345","DOIUrl":"10.1098/rstb.2023.0345","url":null,"abstract":"<p><p>Chronobiology is a multidisciplinary field that extends across the tree of life, transcends all scales of biological organization, and has huge translational potential. For the UK to harness the opportunities presented within applied chronobiology, we need to build our network outwards to reach stakeholders that can directly benefit from our discoveries. In this article, we discuss the importance of biological rhythms to our health, society, economy and environment, with a particular focus on circadian rhythms. We subsequently introduce the vision and objectives of BioClocks UK, a newly formed research network, whose mission is to stimulate researcher interactions and sustain discovery-impact cycles between chronobiologists, wider research communities and multiple industry sectors.This article is part of the Theo Murphy meeting issue 'Circadian rhythms in infection and immunity'.</p>","PeriodicalId":19872,"journal":{"name":"Philosophical Transactions of the Royal Society B: Biological Sciences","volume":"380 1918","pages":"20230345"},"PeriodicalIF":5.4,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11753888/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143024245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jack Munns, Andrew D Beale, Iacovos N Michaelides, Sew Y Peak-Chew, Andrei Mihut, Christine T Major-Styles, Aiwei Zeng, R Ian Storer, Rachel S Edgar, Kevin Moreau, John S O'Neill
{"title":"Development of compounds for targeted degradation of mammalian cryptochrome proteins.","authors":"Jack Munns, Andrew D Beale, Iacovos N Michaelides, Sew Y Peak-Chew, Andrei Mihut, Christine T Major-Styles, Aiwei Zeng, R Ian Storer, Rachel S Edgar, Kevin Moreau, John S O'Neill","doi":"10.1098/rstb.2023.0342","DOIUrl":"10.1098/rstb.2023.0342","url":null,"abstract":"<p><p>The mammalian cryptochrome proteins (CRY1 and CRY2) are transcriptional repressors most notable for their role in circadian transcriptional feedback. Not all circadian rhythms depend on CRY proteins, however, and the CRY proteins are promiscuous interactors that also regulate many other processes. In cells with chronic CRY deficiency, protein homeostasis is highly perturbed, with a basal increase in cellular stress and activation of key inflammatory signalling pathways. Here, we developed tools to delineate the specific effects of CRY reduction, rather than chronic deficiency, to better understand the direct functions of CRY proteins. Performing a bioluminescence screen and immunoblot validation, we identified compounds that resulted in CRY reduction. Using these compounds, we found that circadian PERIOD2 (PER2) protein rhythms persisted under CRY-depleted conditions. By quantitative mass spectrometry, we found that CRY-depleted cells partially phenocopied the proteomic dysregulation of CRY-deficient cells, but showed minimal circadian phenotypes. We did, however, also observe substantial off-target effects of these compounds on luciferase activity and could not ascertain a specific mechanism of action. This work therefore highlights both the utility and the challenges of targeted protein degradation and bioluminescence reporter approaches in disentangling the contribution of CRY proteins to circadian rhythmicity, homeostasis and innate immune regulation.This article is part of the Theo Murphy meeting issue 'Circadian rhythms in infection and immunity'.</p>","PeriodicalId":19872,"journal":{"name":"Philosophical Transactions of the Royal Society B: Biological Sciences","volume":"380 1918","pages":"20230342"},"PeriodicalIF":5.4,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11753880/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143024264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Immune regulation of host energy metabolism and periodicity of malaria parasites.","authors":"Isabella Cristina Hirako, Theresa Ramalho, Ricardo Tostes Gazzinelli","doi":"10.1098/rstb.2023.0511","DOIUrl":"10.1098/rstb.2023.0511","url":null,"abstract":"<p><p>The synchronization of <i>Plasmodium</i> parasites as they replicate within red blood cells of their vertebrate host remains largely unexplored. Understanding this synchronization could reveal how parasites optimize their lifecycle to maximize transmission, evade the immune response and maximize energy acquisition. Rhythmic replication fulfils some criteria of an endogenous oscillator with time of day cues potentially provided by temperature, oxygen levels, hormones and/or nutrient availability. Recent research on a rodent malaria model has highlighted that rhythms associated with the host's feeding/fasting cycle are a crucial factor influencing the synchronization of the erythrocytic stages of <i>Plasmodium</i> to the host's circadian cycle. Innate immune responses are also rhythmic and can regulate host metabolism, suggesting that the innate immune response triggered by <i>Plasmodium</i> contributes to its rhythmic replication. Here, we outline how the interplay between immune responses and metabolism could influence the timing and synchronization of <i>Plasmodium</i>'s replication rhythm, focusing on the roles of the cytokine tumour necrosis factor, mitochondrial function and metabolites generated by the tricarboxylic acid cycle in highly activated monocytes. These processes are pivotal in controlling parasitemia and determining disease outcome, suggesting that a better understanding of energy metabolism on rhythmic host-parasite interactions may provide new insights for therapeutic interventions against malaria.This article is part of the Theo Murphy meeting issue 'Circadian rhythms in infection and immunity'.</p>","PeriodicalId":19872,"journal":{"name":"Philosophical Transactions of the Royal Society B: Biological Sciences","volume":"380 1918","pages":"20230511"},"PeriodicalIF":5.4,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11753876/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143024278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rachel S Edgar, Aidan J O'Donnell, Alan Xiaodong Zhuang, Sarah E Reece
{"title":"Time to start taking time seriously: how to investigate unexpected biological rhythms within infectious disease research.","authors":"Rachel S Edgar, Aidan J O'Donnell, Alan Xiaodong Zhuang, Sarah E Reece","doi":"10.1098/rstb.2023.0336","DOIUrl":"10.1098/rstb.2023.0336","url":null,"abstract":"<p><p>The discovery of rhythmicity in host and pathogen activities dates back to the Hippocratic era, but the causes and consequences of these biological rhythms have remained poorly understood. Rhythms in infection phenotypes or traits are observed across taxonomically diverse hosts and pathogens, suggesting general evolutionary principles. Understanding these principles may enable rhythms to be leveraged in manners that improve drug and vaccine efficacy or disrupt pathogen timekeeping to reduce virulence and transmission. Explaining and exploiting rhythms in infections require an integrative and multidisciplinary approach, which is a hallmark of research within chronobiology. Many researchers are welcomed into chronobiology from other fields after observing an unexpected rhythm or time-of-day effect in their data. Such findings can launch a rich new research topic, but engaging with the concepts, approaches and dogma in a new discipline can be daunting. Fortunately, chronobiology has well-developed frameworks for interrogating rhythms that can be readily applied in novel contexts. Here, we provide a 'how to' guide for exploring unexpected daily rhythms in infectious disease research. We outline how to establish: whether the rhythm is circadian, to what extent the host and pathogen are responsible, the relevance for host-pathogen interactions, and how to explore therapeutic potential.This article is part of the Theo Murphy meeting issue 'Circadian rhythms in infection and immunity'.</p>","PeriodicalId":19872,"journal":{"name":"Philosophical Transactions of the Royal Society B: Biological Sciences","volume":"380 1918","pages":"20230336"},"PeriodicalIF":5.4,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11753885/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143024301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Endocrine and molecular regulation of seasonal avian immune function.","authors":"Sayantan Sur, Jyoti Tiwari, Shalie Malik, Tyler Stevenson","doi":"10.1098/rstb.2023.0507","DOIUrl":"10.1098/rstb.2023.0507","url":null,"abstract":"<p><p>Birds have evolved seasonal adaptations in multiple aspects of the innate and adaptive immune systems. Seasonal immunological adaptations are crucial for survival in harsh environmental conditions and in response to increased prevalence of acute and chronic diseases. Similar to other vertebrates, birds exhibit remarkable plasticity in cytokine production, chemotaxis, phagocytosis and inflammation across the year. In this review, we provide a comparative perspective on seasonal rhythms in bird immune function. We describe advances in our understanding of annual changes in immune cells and responses to innate and adaptive immune challenges. Then, the role of glucocorticoids, sex steroids, thyroid hormones (THs) and melatonin to act as immunomodulators is described. We then discuss the impact of a major and emerging disease, the high pathogenicity avian influenza, as one of the most critical seasonal diseases with significant implications for poultry and wild bird populations. The review identifies the need to enhance our knowledge of annual rhythms in immune cells and tissues in birds, at molecular, cellular and hormonal levels across the year. Moreover, there is a significant absence of information on sex-specific seasonal variation in immune function. Understanding seasonal immune system dynamics will aid in addressing the negative impacts of pathogenic diseases, minimize global economic losses and aid conservation efforts.This article is part of the Theo Murphy meeting issue 'Circadian rhythms in infection and immunity'.</p>","PeriodicalId":19872,"journal":{"name":"Philosophical Transactions of the Royal Society B: Biological Sciences","volume":"380 1918","pages":"20230507"},"PeriodicalIF":5.4,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11753886/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143024274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rory Gibb, David W Redding, Sagan Friant, Kate E Jones
{"title":"Towards a 'people and nature' paradigm for biodiversity and infectious disease.","authors":"Rory Gibb, David W Redding, Sagan Friant, Kate E Jones","doi":"10.1098/rstb.2023.0259","DOIUrl":"10.1098/rstb.2023.0259","url":null,"abstract":"<p><p>Zoonotic and vector-borne infectious diseases are among the most direct human health consequences of biodiversity change. The COVID-19 pandemic increased health policymakers' attention on the links between ecological degradation and disease, and sparked discussions around nature-based interventions to mitigate zoonotic emergence and epidemics. Yet, although disease ecology provides an increasingly granular knowledge of wildlife disease in changing ecosystems, we still have a poor understanding of the net consequences for human disease. Here, we argue that a renewed focus on wildlife-borne diseases as complex socio-ecological systems-a <i>'people and nature'</i> paradigm-is needed to identify local interventions and transformative system-wide changes that could reduce human disease burden. We discuss longstanding scientific narratives of human involvement in zoonotic disease systems, which have largely framed people as ecological disruptors, and discuss three emerging research areas that provide wider system perspectives: how anthropogenic ecosystems construct new niches for infectious disease, feedbacks between disease, biodiversity and social vulnerability and the role of human-to-animal pathogen transmission ('spillback') in zoonotic disease systems. We conclude by discussing new opportunities to better understand the predictability of human disease outcomes from biodiversity change and to integrate ecological drivers of disease into health intervention design and evaluation.This article is part of the discussion meeting issue 'Bending the curve towards nature recovery: building on Georgina Mace's legacy for a biodiverse future'.</p>","PeriodicalId":19872,"journal":{"name":"Philosophical Transactions of the Royal Society B: Biological Sciences","volume":"380 1917","pages":"20230259"},"PeriodicalIF":5.4,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11712283/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142952900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Celebrating 360 years of <i>Philosophical Transactions</i>.","authors":"Richard Dixon, Helen Eaton","doi":"10.1098/rstb.2024.0492","DOIUrl":"10.1098/rstb.2024.0492","url":null,"abstract":"","PeriodicalId":19872,"journal":{"name":"Philosophical Transactions of the Royal Society B: Biological Sciences","volume":"380 1917","pages":"20240492"},"PeriodicalIF":5.4,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11712275/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142952867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Joseph Williamson, Muyang Lu, M Florencia Camus, Richard D Gregory, Ilya M D Maclean, Juan C Rocha, Marjo Saastamoinen, Robert J Wilson, Jon Bridle, Alex L Pigot
{"title":"Clustered warming tolerances and the nonlinear risks of biodiversity loss on a warming planet.","authors":"Joseph Williamson, Muyang Lu, M Florencia Camus, Richard D Gregory, Ilya M D Maclean, Juan C Rocha, Marjo Saastamoinen, Robert J Wilson, Jon Bridle, Alex L Pigot","doi":"10.1098/rstb.2023.0321","DOIUrl":"10.1098/rstb.2023.0321","url":null,"abstract":"<p><p>Anthropogenic climate change is projected to become a major driver of biodiversity loss, destabilizing the ecosystems on which human society depends. As the planet rapidly warms, the disruption of ecological interactions among populations, species and their environment, will likely drive positive feedback loops, accelerating the pace and magnitude of biodiversity losses. We propose that, even without invoking such amplifying feedback, biodiversity loss should increase nonlinearly with warming because of the non-uniform distribution of biodiversity. Whether these non-uniformities are the uneven distribution of populations across a species' thermal niche, or the uneven distribution of thermal niche limits among species within an ecological community, we show that in both cases, the resulting clustering in population warming tolerances drives nonlinear increases in the risk to biodiversity. We discuss how fundamental constraints on species' physiologies and geographical distributions give rise to clustered warming tolerances, and how population responses to changing climates could variously temper, delay or intensify nonlinear dynamics. We argue that nonlinear increases in risks to biodiversity should be the null expectation under warming, and highlight the empirical research needed to understand the causes, commonness and consequences of clustered warming tolerances to better predict where, when and why nonlinear biodiversity losses will occur.This article is part of the discussion meeting issue 'Bending the curve towards nature recovery: building on Georgina Mace's legacy for a biodiverse future'.</p>","PeriodicalId":19872,"journal":{"name":"Philosophical Transactions of the Royal Society B: Biological Sciences","volume":"380 1917","pages":"20230321"},"PeriodicalIF":5.4,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11720646/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142952872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jon Bridle, Andrew Balmford, Sarah M Durant, Richard D Gregory, Richard Pearson, Andy Purvis
{"title":"How should we bend the curve of biodiversity loss to build a just and sustainable future?","authors":"Jon Bridle, Andrew Balmford, Sarah M Durant, Richard D Gregory, Richard Pearson, Andy Purvis","doi":"10.1098/rstb.2023.0205","DOIUrl":"10.1098/rstb.2023.0205","url":null,"abstract":"<p><p>Current rates of habitat and biodiversity loss, and the threat they pose to ecological and economic productivity, would be considered a global emergency even if they were not occurring during a period of rapid anthropogenic climate change. Diversity at all levels of biological organization, both within and among species, and across genomes and communities, is critical for the resilience of the world's ecosystems in the face of such change. However, it remains an urgent scientific challenge to understand how biodiversity underpins these ecological outputs, how patterns of biodiversity are being affected by current threats, and how and where such biodiversity contributes most directly to human economies, well-being and social justice. In addition, even with such scientific understanding, there is a pressing need for societies to incorporate biodiversity protection into their economies and governance, and to stop subsidizing the loss of humanity's future prosperity for short-term private benefit. We highlight key issues and ways forward in these areas, inspired by the research and career of Dame Georgina Mace FRS, and by our discussions during the Royal Society meeting of June 2023.This article is part of the discussion meeting issue 'Bending the curve towards nature recovery: building on Georgina Mace's legacy for a biodiverse future'.</p>","PeriodicalId":19872,"journal":{"name":"Philosophical Transactions of the Royal Society B: Biological Sciences","volume":"380 1917","pages":"20230205"},"PeriodicalIF":5.4,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11712268/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142952921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}