Integrative Biology Research Articles

Structural Plasticity within 3-Hydroxy-3-Methylglutaryl Synthases Catalyzing the First Step of β-Branching in Polyketide Biosynthesis Underpins a Dynamic Mechanism of Substrate Accommodation.

Understanding how enzymes have been repurposed by evolution to carry out new functions is a key goal of mechanistic enzymology. In this study we aimed to identify the adaptations required to allow the 3-hydroxy-3-methylglutaryl (HMG)-CoA synthase (HMGCS) enzymes of primary isoprenoid assembly to function in specialized polyketide biosynthetic pathways, where they initiate β-branching. This role notably necessitates that the HMG synthases (HMGSs) act on substrates tethered to noncatalytic acyl carrier protein (ACP) domains instead of coenzyme A, and accommodation of substantially larger chains within the active sites. Here, we show using a combination of X-ray crystallography and small-angle X-ray scattering, that a model HMGS from the virginiamycin system exhibits markedly increased flexibility relative to its characterized HMGCS counterparts. This mobility encompasses multiple secondary structural elements that define the dimensions and chemical nature of the active site, as well the catalytic residues themselves. This result was unexpected given the well-ordered character of the HMGS within the context of an HMGS/ACP complex, but analysis by synchrotron radiation circular dichroism demonstrates that this interaction leads to increased HMGS folding. This flexible to more rigid transition is notably not accounted for by AlphaFold2, which yielded a structural model incompatible with binding of the native substrates. Taken together, these results illustrate the continued necessity of an integrative structural biology approach combining crystallographic and solution-phase data for elucidating the mechanisms underlying enzyme remodeling, information which can inform strategies to replicate such evolution effectively in the laboratory.

The effect of ship-induced wave trains on periphytic algal communities in the littoral zone of a large regulated river (River Danube, Austria)

Riverine ecosystems are profoundly influenced by hydrological dynamics and natural flow regimes, which dictate the temporal variability of water levels and the amplitude of fluctuations. Human activities, particularly navigation and hydropower generation, have significantly altered these natural patterns, leading to detrimental impacts on the physical, chemical, and biological integrity of river ecosystems. The littoral zone, in particular, is highly susceptible to anthropogenic disturbances, experiencing disruptions in biological activity and biogeochemical processes. This study evaluates the effects of ship-induced wave trains on the structural and functional properties of periphytic algal communities in a regulated river environment. Using data from the Austrian Danube River, periphytic algae's immediate and long-term responses to wave events generated by different types of ships were investigated. Immediate reactions of periphytic algae to wave trains were characterized by reductions in the effective quantum yield of PS II, indicating stress-induced down-regulation of photosystem II photochemistry. Abrasion and remobilization of periphytic algae due to wave action led to increased resuspension of chlorophyll-a into the water column. Furthermore, ship-induced wave trains influenced the pigment composition of periphyton, with photoprotective mechanisms being activated in response to fluctuating light conditions. Long-term effects of wave impact on periphytic algae biomass varied depending on water depth and exposure to aerial stress. While wave action mitigated desiccation stress in shallow areas, it resulted in biomass reduction and alterations in community composition in deeper zones. Notably, the occurrence of diatoms decreased in wave-impacted areas, potentially shifting the community towards Chlorophyceae dominance. Overall, this study underscores the complexity of ship-induced wave impacts on riverine ecosystems and highlights the importance of considering both immediate and long-term responses of periphytic algal communities. Understanding these dynamics is crucial for informing sustainable management strategies aimed at mitigating the adverse effects of navigation activities on riverine biodiversity and ecosystem functioning.

Estimation of the ecological integrity of the Guadiana River using Partial Least Squares Path Modelling and simulation scenarios

Ecological integrity is fundamental to human life and ecosystems, so its assessment and management are crucial. This concept assesses ecosystem health by examining physico-chemical and biological characteristics, riparian vegetation and macroinvertebrate communities. In recent decades, water resources have undergone significant changes due to various factors that have contributed to the physical, chemical and biological pollution of water. To address this problem, a specific model has been developed using the Partial Least Squares Path Modelling methodology to analyse and quantify the main factors affecting the ecological integrity of the Spanish part of the Guadiana River (Spain). The variables analysed at the different sampling points in the catchment include forest cover, anthropogenic pressure, water quality and biological integrity. Water quality and biological integrity, in turn, constitute the concept of ecological integrity. The model predicts 60.3 % of the physico-chemical water quality and 56.6 % of the biological integrity, showing that ¨Forest cover¨ negatively impacts water quality (W = −0.476) by reducing pollution, while ¨Anthropogenic Pressure¨ positively impacts it (W = 0.680) by increasing pollution. Based on the modelling, three future scenarios were designed, from the lowest to the highest pressure considering changes in riparian forest quality based on QBR and changes in the number of reservoirs: a favourable scenario with high riparian forest quality and no reservoirs; an intermediate scenario with good riparian forest quality and no change in the number of reservoirs; and an unfavourable scenario, characterised by very poor riparian forest quality and an increase in the number of reservoirs. In this context, the importance of the conservation and enhancement of riparian vegetation as a nature-based solution is highlighted, as well as the pressure generated by industrial activity and agricultural practices on the ecological integrity of the study area. The favourable scenario, with very good quality riparian vegetation, improves water quality by up to 85 %, positively impacting the ecological integrity of the river. In contrast, the unfavourable scenario, with extremely degraded riparian forest, would decrease water quality by up to 62 %, negatively affecting ecological integrity. Modelling and future scenarios is an essential tool in the decision-making process to improve environmental governance and water security. In addition, the PLS-PM methodology allows the identification and quantification of relationships between complex variables, providing a solid basis for the design of effective environmental management strategies.

Exploring protein structural ensembles: Integration of sparse experimental data from electron paramagnetic resonance spectroscopy with molecular modeling methods.

Under physiological conditions, proteins continuously undergo structural fluctuations on different timescales. Some conformations are only sparsely populated, but still play a key role in protein function. Thus, meaningful structure-function frameworks must include structural ensembles rather than only the most populated protein conformations. To detail protein plasticity, modern structural biology combines complementary experimental and computational approaches. In this review, we survey available computational approaches that integrate sparse experimental data from electron paramagnetic resonance spectroscopy with molecular modeling techniques to derive all-atom structural models of rare protein conformations. We also propose strategies to increase the reliability and improve efficiency using deep learning approaches, thus advancing the field of integrative structural biology.

Advancing Sustainable Agriculture: Next-Generation Biofertilizers through Synthetic Biology and Nanoparticle Integration

Advancing Sustainable Agriculture: Next-Generation Biofertilizers through Synthetic Biology and Nanoparticle Integration

The path to the G protein-coupled receptor structural landscape: Major milestones and future directions.

G protein-coupled receptors (GPCRs) play a crucial role in cell function by transducing signals from the extracellular environment to the inside of the cell. They mediate the effects of various stimuli, including hormones, neurotransmitters, ions, photons, food tastants and odorants, and are renowned drug targets. Advancements in structural biology techniques, including X-ray crystallography and cryo-electron microscopy (cryo-EM), have driven the elucidation of an increasing number of GPCR structures. These structures reveal novel features that shed light on receptor activation, dimerization and oligomerization, dichotomy between orthosteric and allosteric modulation, and the intricate interactions underlying signal transduction, providing insights into diverse ligand-binding modes and signalling pathways. However, a substantial portion of the GPCR repertoire and their activation states remain structurally unexplored. Future efforts should prioritize capturing the full structural diversity of GPCRs across multiple dimensions. To do so, the integration of structural biology with biophysical and computational techniques will be essential. We describe in this review the progress of nuclear magnetic resonance (NMR) to examine GPCR plasticity and conformational dynamics, of atomic force microscopy (AFM) to explore the spatial-temporal dynamics and kinetic aspects of GPCRs, and the recent breakthroughs in artificial intelligence for protein structure prediction to characterize the structures of the entire GPCRome. In summary, the journey through GPCR structural biology provided in this review illustrates how far we have come in decoding these essential proteins architecture and function. Looking ahead, integrating cutting-edge biophysics and computational tools offers a path to navigating the GPCR structural landscape, ultimately advancing GPCR-based applications.

Genetic enhancement from the perspective of transhumanism: exploring a new paradigm of transhuman evolution.

Transhumanism is a movement that advocates for the enhancement of human capabilities through the use of advanced technologies such as genetic enhancement. This article explores the definition, history, and development of transhumanism. Then, it compares the stance on genetic enhancement from the perspectives of bio-conservatism, bio-liberalism, and transhumanism. This article posits that transhuman evolution has twofold implications, allowing for the integration of transhumanist research and evolutionary biology. First, it offers a compelling scientific framework for understanding genetic enhancement, avoiding technological progressivism, and incorporating concepts of evolutionary biology. Second, it represents a new evolutionary paradigm distinct from traditional Lamarckism and Darwinism. It marks the third synthesis of evolutionary biology, offering fresh perspectives on established concepts such as artificial selection and gene-culture co-evolution. In recent decades, human enhancement has captivated not only evolutionary biologists, neurobiologists, psychologists, and philosophers, but also those in fields such as cybernetics and artificial intelligence. In addition to genetic enhancement, other human enhancement technologies, including brain-computer interfaces and brain uploading, are currently under development, which the paradigm of transhuman evolution can better integrate into its framework.

Dynamics Behaviours of Kink Solitons in Conformable Kolmogorov–Petrovskii–Piskunov Equation

The current study introduces the generalised New Extended Direct Algebraic Method (gNEDAM) for producing and examining propagation of kink soliton solutions within the framework of the Conformable Kolmogorov–Petrovskii–Piskunov Equation (CKPPE), which entails conformable fractional derivatives into account. The primary justification around employing conformable derivatives in this study is their special ability to comply with the chain rule, allowing for in the solution of aimed nonlinear model. The CKPPE is a crucial model for a number of disciplines, such as mathematical biology, reaction-diffusion mechanisms, and population increase. CKPPE is transformed into a Nonlinear Ordinary Differential Equation by the proposed gNEDAM, and many kink soliton solutions are found by applying the series form solution. These kink soliton solutions shed light on propagation mechanisms within the framework of the CKPPE model. Furthermore, our research offers multiple graphical depictions that facilitate the examination and analysis of the propagation patterns of the identified kink soliton solutions. Through the integration of mathematical biology and reaction-diffusion principles, our research broadens our comprehension of intricate occurrences in various academic domains.

Effect of nirsevimab on hospitalisations for respiratory syncytial virus bronchiolitis in France, 2023–24: a modelling study

Respiratory syncytial virus (RSV) is a major cause of hospitalisations and deaths among infants worldwide. France was one of the first countries to implement a national programme (beginning on Sept 15, 2023) for administration of nirsevimab, a single-dose long-acting monoclonal antibody treatment, to infants born on or after Feb 6, 2023, to prevent lower respiratory tract infection caused by RSV. We aimed to estimate the effectiveness of nirsevimab and the number of hospitalisations averted in children younger than 24 months in real-world settings. In this modelling study, we developed an age-structured deterministic model characterising RSV transmission as well as plausible scenarios for the administration of nirsevimab doses based on maternity ward and community pharmacy supply data. We retrospectively estimated nirsevimab effectiveness in infants younger than 24 months during the 2023-24 RSV season in France (excluding overseas territories) and the number of averted hospitalisations for RSV bronchiolitis occurring after emergency department visits, by calibrating the model to hospital and virological surveillance data from Aug 21, 2017, to Feb 4, 2024, alongside serological data from a previous cross-sectional study. To assess the robustness of our estimates, we conducted sensitivity analyses in which we modified our assumptions about the number of doses administered, the reconstruction of the number of RSV-associated hospitalisations for bronchiolitis, the duration of maternal and post-infection immunity to RSV, and the number of contacts in children aged 0-2 months. We estimated that nirsevimab administration prevented 5800 (95% credible interval 3700-7800) RSV-associated hospitalisations for bronchiolitis after emergency department visits among children younger than 24 months, including 4200 (2900-5600) hospitalisations among those aged 0-2 months, between Sept 15, 2023 (the date nirsevimab was introduced), and Feb 4, 2024-a 23% (16-30) reduction in the total number of hospitalisations and a 35% (25-44) reduction in the 0-2 months age group, compared with the scenario without administration. In our baseline scenario, in which we estimated that 215 000 doses of nirsevimab were administered by Jan 31, 2024, the estimated effectiveness against RSV-associated hospitalisations for bronchiolitis was 73% (61-84), corresponding to one hospitalisation averted for every 39 (26-54) doses administered. In sensitivity analyses, nirsevimab remained effective against RSV-associated hospitalisations for bronchiolitis after emergency department attendance. Our findings show that nirsevimab administration campaigns could effectively reduce the RSV-related hospital burden of bronchiolitis in children younger than 24 months. European Commission, Laboratoire d'Excellence Integrative Biology of Emerging Infectious Diseases programme, and INCEPTION project.

Enhancing Drug Discovery and Development through the Integration of Medicinal Chemistry, Chemical Biology, and Academia-Industry Partnerships: Insights from Roche's Endocannabinoid System Projects.

The endocannabinoid system (ECS) is a critical regulatory network composed of endogenous cannabinoids (eCBs), their synthesizing and degrading enzymes, and associated receptors. It is integral to maintaining homeostasis and orchestrating key functions within the central nervous and immune systems. Given its therapeutic significance, we have launched a series of drug discovery endeavors aimed at ECS targets, including peroxisome proliferator-activated receptors (PPARs), cannabinoid receptors types 1 (CB1R) and 2 (CB2R), and monoacylglycerol lipase (MAGL), addressing a wide array of medical needs. The pursuit of new therapeutic agents has been enhanced by the creation of specialized labeled chemical probes, which aid in target localization, mechanistic studies, assay development, and the establishment of biomarkers for target engagement. By fusing medicinal chemistry with chemical biology in a comprehensive, translational end-to-end drug discovery strategy, we have expedited the development of novel therapeutics. Additionally, this strategy promises to foster highly productive partnerships between industry and academia, as will be illustrated through various examples.

Assessing stream biological integrity across gradients of flow permanence and hydrologic connectivity

Assessing stream biological integrity across gradients of flow permanence and hydrologic connectivity

Tumor biology experimental course design based on the integration of molecular biology and metabolomics

Tumor biology experimental course design based on the integration of molecular biology and metabolomics

Evaluating the Success of Preformed Resin Bonded Composite Strip Crowns for the Primary Central Incisor in Restoring Carious Primary Canine Teeth: A Retrospective Analysis.

Background Restoration of primary canine teeth in pediatric dentistry requires a balance of functional, biological, and esthetic factors. Stainless steel crowns, while effective for posterior restorations, often have patient acceptance issues due to esthetic limitations. Resin-bonded composite strip crowns have gained traction for anterior restorations due to their superior esthetic qualities and repairability. However, their long-term performance in primary canines characterized by unique morphological and functional demands has not been thoroughly evaluated. This study investigates the efficacy of resin-bonded incisor strip crowns in primary canines over three years, assessing their functional durability, biological integrity, and esthetic performance to provide a comprehensive evaluation of their long-term success in this application. Methods This retrospective observational study, conducted from September 2023 to December 2023 at the Department of Pediatric and Preventive Dentistry, Saveetha Dental College and Hospitals, Chennai, Tamil Nadu, India, received ethical approval from the Institutional Human Ethical Committee (IHEC/SDC/PEDO-2103/23/131). Dental records from January 2020 to December 2020 were reviewed by two investigators to identify children aged six years or younger who had undergone pulpectomy in primary canine teeth and were restored with resin-bonded incisor strip crowns. Exclusions included records with missing contact details or post-treatment radiographs. The purpose was to ensure a three-year review period when contacting patients in 2023. Eligible parents were contacted by phone, informed about the study, and invited for a review. Informed consent was obtained in person. Children with exfoliated primary canines and those whose parents did not sign the consent form were excluded. The restored crowns were evaluated using World Dental Federation (FDI) criteria across functional, biological, and esthetic domains by two calibrated examiners. Statistical analysis was conducted using IBMSPSSStatistics for Windows, Version 24 (Released 2016; IBM Corp., Armonk, New York, United States), with categorical variables expressed as n (%), inter-examiner reliability assessed by Cohen's kappa, and chi-square test used for goodness of fit, setting significance at 95%. Results Of the 92 primary canines restored with resin-bonded incisor strip crowns, 60 children were evaluated. The retention rate at the three-year follow-up was 50 (83.3%). Functional evaluation revealed that 48 (80%) of crowns maintained surface texture, 42 (70%) preserved form and contour, and 52 (86.6%) demonstrated acceptable occlusion and wear. Biologically, 55 (91.7%) of the crowns had no secondary caries, and 56 (93.4%) had no dental hard tissue defects at the margin. Esthetically, 48 (80%) of crowns retained surface texture, 46 (76.6%) had a satisfactory color match, and 45 (71.6%) exhibited minimal marginal staining. Statistical analysis confirmed significant results for all functional and esthetic parameters (p < 0.05). Conclusion The technique of placing incisor strip crowns in the place of primary canines can be recommended considering its maintenance of functional, biological, and esthetic properties.

A bacteria-based index of biotic integrity assesses aquatic ecosystems effectively in rewetted long-term dry river channel after water replenishment.

Climate-induced droughts exert a significant influence on the connectivity of river systems. It is estimated that about 25% of the world's rivers ran dry before reaching the ocean due to climate change and human activities. Ecological water replenishment is an effective measure for restoring aquatic ecosystems damaged by drought. It is urgently needed to quantitatively assess the aquatic ecosystems in rewetted dry river channels after water replenishment. This study investigated the variations in phytoplankton, zooplankton, benthic macroinvertebrates, and benthic bacterial communities in the rewetted dry river channel of Yongding River after water replenishment. In comparison with the water column communities, the benthic macroinvertebrates were identified as limiting factors for ecological restoration in rewetted dry river channels. In the absence of a certain recovery time for benthic macroinvertebrates, the benthic bacterial-based index of biological integrity, especially calculated based on their intrinsic properties, can properly assess aquatic ecosystems in rewetted dry river channels.

Homocysteine Thiolactone Detoxifying Enzymes and Alzheimer's Disease.

Elevated levels of homocysteine (Hcy) and related metabolites are associated with Alzheimer's disease (AD). Severe hyperhomocysteinemia causes neurological deficits and worsens behavioral and biochemical traits associated with AD. Although Hcy is precluded from entering the Genetic Code by proofreading mechanisms of aminoacyl-tRNA synthetases, and thus is a non-protein amino acid, it can be attached to proteins via an N-homocysteinylation reaction mediated by Hcy-thiolactone. Because N-homocysteinylation is detrimental to a protein's function and biological integrity, Hcy-thiolactone-detoxifying enzymes-PON1, BLMH, BPHL-have evolved. This narrative review provides an account of the biological function of these enzymes and of the consequences of their impairments, leading to the phenotype characteristic of AD. Overall, accumulating evidence discussed in this review supports a hypothesis that Hcy-thiolactone contributes to neurodegeneration associated with a dysregulated Hcy metabolism.

Multidrug-Resistant Escherichia coli Accumulated by Freshwater Bivalves: An Underestimated Risk for Public Health?

As bioindicators, freshwater bivalves are crucial for the assessment of the contamination impact on different levels of biological integration. Escherichia coli is used as a bioindicator of water fecal contamination, representing a critical global concern, especially with the rise of multidrug-resistant (MDR) strains. Phylogenetic diversity, pathotypic characterization, and antibiotic resistance profiles of E. coli isolated from freshwater bivalves (Anodonta anatina) were assessed. Samples were collected from the Tua River in Northern Portugal, from two different sites, Chelas and Barcel, representing different degrees of contamination. Antimicrobial susceptibility testing was performed by the disk diffusion method, and characterizations of the phylogenetic groups and pathotypes were assessed by PCR-multiplex and real-time PCR-multiplex, respectively. Results showed that 60% of isolates were characterized as MDR, including resistance to carbapenems, considered the last resort against multidrug-resistant bacteria. Within this study, it was also possible to verify the antimicrobial resistance (AMR) profile differences between the two sampling sites, with bivalve isolates from the Chelas site showing a higher percentage of antibiotic resistance. Among the E. coli isolates, the highest prevalence (55%) was observed in group B1, followed by group D or E (15%), group A (10%), and group E or Clade I (10%). None of the isolates were classified as diarrheagenic E. coli (DEC). This work highlights the potential transmission of antimicrobial-resistant bacteria through bivalves in the food chain. The 'One Health' approach is crucial for combating antimicrobial resistance, namely in edible freshwater species, emphasizing active surveillance to protect human, animal, and environmental health against the spread of antibiotic-resistant bacteria in aquatic environments.

Multiomics unveils extracellular vesicle-driven mechanisms of endothelial communication in human carotid atherosclerosis.

Background: Carotid atherosclerosis is orchestrated by cell-cell communication that drives progression along a clinical continuum (asymptomatic to symptomatic). Extracellular vesicles (EVs) are cell-derived nanoparticles representing a new paradigm in cellular communication. Little is known about their biological cargo, cellular origin/destination, and functional roles in human atherosclerotic plaque. Methods: EVs were enriched via size exclusion chromatography from human carotid endarterectomy samples dissected into paired plaque and marginal zones (symptomatic n=16, asymptomatic n=13). EV cargos were assessed via whole transcriptome miRNA sequencing and mass spectrometry-based proteomics. EV multi-omics were integrated with bulk and single cell RNA-sequencing (scRNA-seq) datasets to predict EV cellular origin and ligand-receptor interactions, and multi-modal biological network integration of EV-cargo was completed. EV functional impact was assessed with endothelial angiogenesis assays. Results: Carotid plaques contained more EVs than adjacent marginal zones, with differential enrichment for EV-miRNAs and EV-proteins in key atherogenic pathways. EV cellular origin analysis suggested that tissue EV signatures originated from endothelial cells (EC), smooth muscle cells (SMC), and immune cells. Integrated tissue vesiculomics and scRNA-seq indicated complex EV-vascular cell communication that changed with disease progression and plaque vulnerability (i.e., symptomatic disease). Plaques from symptomatic patients, but not asymptomatic patients, were characterized by increased involvement of endothelial pathways and more complex ligand-receptor interactions, relative to their marginal zones. Plaque-EVs were predicted to mediate communication with ECs. Pathway enrichment analysis delineated an endothelial signature with roles in angiogenesis and neovascularization - well-known indices of plaque instability. This was validated functionally, wherein human carotid symptomatic plaque EVs induced sprouting angiogenesis in comparison to their matched marginal zones. Conclusion: Our findings indicate that EVs may drive dynamic changes in plaques through EV- vascular cell communication and effector functions that typify vulnerability to rupture, precipitating symptomatic disease. The discovery of endothelial-directed angiogenic processes mediated by EVs creates new therapeutic avenues for atherosclerosis.

Enabling Lignin Valorization Through Integrated Advances in Plant Biology and Biorefining.

Despite lignin having long been viewed as an impediment to the processing of biomass for the production of paper, biofuels, and high-value chemicals, the valorization of lignin to fuels, chemicals, and materials is now clearly recognized as a critical element for the lignocellulosic bioeconomy. However, the intended application for lignin will likely require a preferred lignin composition and form. To that end, effective lignin valorization will require the integration of plant biology, providing optimal feedstocks, with chemical process engineering, providing efficient lignin transformations. Recent advances in our understanding of lignin biosynthesis have shown that lignin structure is extremely diverse and potentially tunable, while simultaneous developments in lignin refining have resulted in the development of several processes that are more agnostic to lignin composition. Here, we review the interface between in planta lignin design and lignin processing and discuss the advances necessary for lignin valorization to become a feature of advanced biorefining.

Discovery of a Therapeutic Agent for Glioblastoma Using a Systems Biology-Based Drug Repositioning Approach.

Glioblastoma (GBM), a highly malignant tumour of the central nervous system, presents with a dire prognosis and low survival rates. The heterogeneous and recurrent nature of GBM renders current treatments relatively ineffective. In our study, we utilized an integrative systems biology approach to uncover the molecular mechanisms driving GBM progression and identify viable therapeutic drug targets for developing more effective GBM treatment strategies. Our integrative analysis revealed an elevated expression of CHST2 in GBM tumours, designating it as an unfavourable prognostic gene in GBM, as supported by data from two independent GBM cohorts. Further, we pinpointed WZ-4002 as a potential drug candidate to modulate CHST2 through computational drug repositioning. WZ-4002 directly targeted EGFR (ERBB1) and ERBB2, affecting their dimerization and influencing the activity of adjacent genes, including CHST2. We validated our findings by treating U-138 MG cells with WZ-4002, observing a decrease in CHST2 protein levels and a reduction in cell viability. In summary, our research suggests that the WZ-4002 drug candidate may effectively modulate CHST2 and adjacent genes, offering a promising avenue for developing efficient treatment strategies for GBM patients.

Establishment and activity of the planning and acting network for low dose radiation research in Japan (PLANET): 2016-2023.

The Planning and Acting Network for Low Dose Radiation Research in Japan (PLANET) was established in 2017 in response to the need for an all-Japan network of experts. It serves as an academic platform to propose strategies and facilitate collaboration to improve quantitative estimation of health risks from ionizing radiation at low-doses and low-dose-rates. PLANET established Working Group 1 (Dose-Rate Effects in Animal Experiments) to consolidate findings from animal experiments on dose-rate effects in carcinogenesis. Considering international trends in this field as well as the situation in Japan, PLANET updated its priority research areas for Japanese low-dose radiation research in 2023 to include (i) characterization of low-dose and low-dose-rate radiation risk, (ii) factors to be considered for individualization of radiation risk, (iii) biological mechanisms of low-dose and low-dose-rate radiation effects and (iv) integration of epidemiology and biology. In this context, PLANET established Working Group 2 (Dose and Dose-Rate Mapping for Radiation Risk Studies) to identify the range of doses and dose rates at which observable effects on different endpoints have been reported; Working Group 3 (Species- and Organ-Specific Dose-Rate Effects) to consider the relevance of stem cell dynamics in radiation carcinogenesis of different species and organs; and Working Group 4 (Research Mapping for Radiation-Related Carcinogenesis) to sort out relevant studies, including those on non-mutagenic effects, and to identify priority research areas. These PLANET activities will be used to improve the risk assessment and to contribute to the revision of the next main recommendations of the International Commission on Radiological Protection.