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    Disciplines / Research questions

    Biology

    98 research topics · 322 questions

    The puzzle of mammalian dispersal4 questions

    1. Realistic species-specific dispersal in projections of mammal responses to climate change: making landscape- and habitat-informed movement models feasible for many species and determining whether simplified dispersal assumptions under- or over-estimate the ability of mammals to keep pace

    2. Historical versus contemporary drivers of Western Hemisphere mammal community structure: fossil-inclusive, multi-scale attribution with robust null-model and biogeographic inference

    3. The unmeasured long-distance tail of mammalian natal dispersal kernels and the unvalidated causal basis of trait-based dispersal-distance prediction

    4. Open questions from Höner et al. (2007) on female mate choice as the driver of male-biased dispersal in social mammals: generality, mechanism, alternatives, genetic consequences, and male assessment

    Why is addiction often difficult to completely quit?3 questions

    1. Incubation of craving in methamphetamine use disorder: within-subject longitudinal confirmation and causal test of medial prefrontal beta synchrony

    2. Addiction-like switch from palatable-food preference to drug preference in a minority of rats under long-term self-administration training

    3. Causal mechanism linking elevated GluA1 translation to synaptic CP-AMPAR accumulation in nucleus accumbens core during incubation of methamphetamine craving

    How is the brain vascular network formed?2 questions

    1. Mechanisms of hindbrain vascular network assembly and patterning: chemokine-guided central artery targeting, CXCR4 effector pathways, metameric positioning cues, and vertebrate conservation of basilar artery assembly

    2. How endothelial Wnt/β-catenin signaling counteracts S1pr1–Rac1 signaling to enable VE-cadherin-mediated anastomosis of brain capillaries: the molecular locus, trafficking mechanism, developmental switch, and scope of the module

    How is cholesterol transported within cells?3 questions

    1. In vivo partitioning and mechanism of nonvesicular plasma membrane-to-ER sterol transport in yeast: division of labor among Osh/ORP, Lam/Ltc, and BLTP2 sterol-transfer routes and the ABC-transporter mobilization mechanism

    2. Mechanism and regulation of cholesterol transport across lysosome–peroxisome membrane contacts (Syt7–PI(4,5)P2 LPMC), and its contribution to peroxisomal-disorder pathology

    3. How does LDL-derived cholesterol cross lysosomal membrane contact sites — the transfer mechanism at the ER-lysosome interface, the mitochondrial anchor of STARD3, and the regulation of the competing contact-site populations?

    What is the intrinsic relationship between protein dynamics and function?3 questions

    1. The timescale dichotomy of protein dynamics: how fast conformational fluctuations couple to slow functional cycles

    2. Establishing or refuting whether true reaction coordinates from the generalized work functional determine protein biological activity: testable confirmation, generality, and theoretical grounding of the structure-function roadmap

    3. Causal mechanism of long-range allostery in the lac repressor: dynamics-mediated switching versus two-state conformational pre-equilibrium

    How have protein 3D structures and functions evolved?3 questions

    1. Mechanistic basis of the divergence limit that molecular-function conservation imposes on billion-year protein evolution

    2. Evolutionary pathway of the bacteriophage Cro fold switch: phylogenetic placement, mutational trajectory, and timing of dimerization evolution

    3. Tempo and mode of the birth of new protein structural architectures: the genomic origin of new common structural ancestors and whether the protein structure space is still expanding or has reached equilibrium

    Why are low-temperature methanogens cold-resistant?2 questions

    1. Mechanistic validation of the temperature-responsive proteome of the psychrophilic archaeon Methanococcoides burtonii: cell-envelope remodeling, compartmentalized RNA metabolism, and heat-associated oxidative stress

    2. Identity and cold-activation mechanism of the mtaC2 5'UTR-processing endoribonuclease in the psychrophilic methanogen Methanolobus psychrophilus R15

    Mate choice and mating systems in animals4 questions

    1. Open extensions of the genic game model of rodent mating-system evolution: reversible transitions, genetic architecture, and discriminating tests against resource ecology

    2. Mechanism linking social mating system to burst-like testes-mass diversification across vertebrates, and why only monogamous birds show sustained directional testes-mass reduction

    3. Robustness and empirical status of preference cycling driven by coevolved male and female mate choice

    4. When does sexual selection through mate choice deplete versus exaggerate genetic variation: the unresolved scope of Xu and Servedio's variance-exaggeration resolution of the lek paradox

    Could interspecific natural hybridization in animals be one of the drivers of new species formation?7 questions

    1. The evolutionary fate of the hybridizing Geospiza fortis–G. fuliginosa complex on Daphne Major: fusion, stable admixture, reversal, or a new trajectory?

    2. Drivers, network structure, and timing of extensive multi-species hybridization in a southern Ontario Leuciscidae minnow assemblage

    3. Hybridization as a speciation motor: causal function of introgressed alleles in the Lake Victoria cichlid radiation and the generality of hybridization-fueled adaptive radiation

    4. The generality and conditions of homoploid hybrid speciation in animals: the open agenda set by Heliconius heurippa

    5. Does natural interspecific hybridization in animals, on balance, promote speciation or erode species boundaries? Quantifying the incidence, limits, and net diversification consequences of gene exchange across animal groups

    6. Conditions and evidentiary standards for homoploid hybrid speciation in animals

    7. Is hybridization a general macroevolutionary driver of accelerated diversification in animals, and what role does reinforcement play?

    How are concentration gradients of morphogens established and responded to in animal embryos?3 questions

    1. Molecular basis of nuclear-cycle memory and multi-state promoter kinetics in Dorsal-mediated patterning of the Drosophila embryo

    2. Molecular mechanism of time-integration decoding of the dynamic BMP gradient in the early Drosophila embryo: Zen-dependent competence and spatial restriction of target-gene activation

    3. Rate-limiting molecular steps of the receptor-mediated sink in Fgf8 morphogen gradient formation

    How are organ morphology and size controlled in animals?4 questions

    1. Molecular implementation of morphogen-gradient size scaling and size-matched growth control during axolotl limb regeneration

    2. Molecular control of differential extracellular-matrix growth anisotropy between tissue layers, and completion of the mechanical model, in the developing Drosophila wing disc

    3. What mechanism limits pancreas size by embryonic progenitor cell number, and how general is progenitor-number-limited versus regulative organ size control?

    4. Molecular initiation of the apex-to-base Cdkn1b (p27Kip1) transcriptional wave and coordinated Yap/Tead inactivation in organ of Corti progenitors

    What is the regulatory network for time rhythms within animal bodies?4 questions

    1. Molecular identity and quantitative mechanism of the intercellular coupling that synchronizes hepatocyte circadian clocks in the mammalian liver

    2. Molecular and cellular mechanisms of state-dependent GABAA_A signaling and shell-to-core communication in the suprachiasmatic nucleus circadian clock network

    3. Validating interaction-level mechanisms of circadian timekeeping: dual-function transcription factors, NMO-PER-TIM-SGG complex assembly, VIP-dependent single-cell bistability, and the mathematics of the DeWoskin-Geng-Stinchcombe-Forger models

    4. Functional and tissue-specific validation of the mammalian circadian clock's regulation of cancer-related genes and miRNAs in the NCRG network, including the proposed NCL–RORγ–miRNA axis

    What is the role of polyploidy in plant speciation?3 questions

    1. Mechanistic origins and generality of abiotic niche shifts in allopolyploid plants relative to their diploid progenitors

    2. Whole-genome duplication and the uncoupling of polyploidy from diversification in Australian Pomaderreae (Rhamnaceae): detecting and dating ancient WGD events and explaining why polyploidy tracks species richness but not tip diversification rates

    3. Long-term fate of polyploid plant lineages: do persisting polyploids attain elevated diversification, and what rates and mechanisms govern their macroevolutionary success?

    Hydrogen production by fermentation vs. microbial electrolysis cells2 questions

    1. Scaling and mechanistic validation of the two-stage dark fermentation-microbial electrolysis (DF-MEC) cascade for biohydrogen production from agro-industrial wastewaters

    2. Sustained hydrogen production from complex dairy-type substrates in single-chamber microbial electrolysis cells: methane-source attribution, suppression of hydrogen scavengers, and real-wastewater scale-up validation

    Are mayflies the earliest diverged winged insects?10 questions

    1. The Palaeoptera problem: robustly resolving the basal pterygote divergence among Ephemeroptera, Odonata, and Neoptera

    2. The Palaeoptera problem: the earliest branching order of winged insects (Ephemeroptera, Odonata, Neoptera)

    3. The Palaeoptera problem: resolving the basal branching of winged insects (Ephemeroptera, Odonata, Neoptera) and testing the proposed head-character synapomorphies

    4. The Palaeoptera problem: resolving the deepest splits among the winged insects (Ephemeroptera, Odonata, Neoptera), with implications for the origin of insect wings

    5. The basal pterygote divergence (the Palaeoptera problem): the branching order of Ephemeroptera, Odonata, and Neoptera

    6. The deep skeleton of winged-insect phylogeny: resolving the Palaeoptera problem, the polyneopteran ordinal backbone, and the Eumetabola node

    7. Taxonomic generality of biomechanically inferred mechanical linkages among insect head characters and their power to resolve basal pterygote relationships (the Palaeoptera problem)

    8. The Palaeoptera problem and the basal hexapod backbone: resolving the relationships of Ephemeroptera, Odonata, Neoptera, and the early-diverging hexapod lineages (Diplura, Collembola, Protura)

    9. Ancestral condition of the pterygote wing base: character polarity from Odonata wing-base homology and the unresolved basal divergence of winged insects

    10. Resolving the basal pterygote branching order (the Palaeoptera problem) and the reliability of mitochondrial-genome inference for Ephemeroptera, Odonata, and Neoptera

    The complex human transcriptome2 questions

    1. The deep complexity of the human transcriptome: completing the rare-transcript repertoire, establishing the functional significance of low-abundance transcripts, and quantifying cell-to-cell transcriptomic heterogeneity (Mercer et al. 2012)

    2. The catalog-to-function gap for human long noncoding RNAs: complete full-length transcript structures, resolved coding potential, and causal functional validation of the annotated lncRNA landscape

    Induced stem-cell differentiation and neural tissue repair and regeneration1 questions

    1. Mechanism, long-term tumorigenicity, and human/non-human primate efficacy of iPSC-derived neural stem cell transplantation for multiple sclerosis

    The mystery of oxygen release in photosynthesis9 questions

    1. Electronic structure of the S2S_2 state of the photosystem II oxygen-evolving complex: reconciling manganese oxidation-state assignments with the complete spectroscopic fingerprint

    2. Completing the dynamic mechanism of the photosystem II oxygen-evolving complex: experimental verification of the predicted S2→S3_2\to S_3 branching pathways and the dioxygen-forming S4_4 step

    3. Definitive exclusion or validation of the Mn(VII) dioxo mechanism for O–O bond formation in photosystem II

    4. Mechanism of O–O bond formation at the oxygen-evolving complex of photosystem II: substrate-oxygen identity and the electronic structure of the final (S4) oxidation state

    5. O–O bond formation in the photosystem II S3→[S4]→S0S_3\to[S_4]\to S_0 transition: the reduced intermediate, the substrate oxygen pair, and ligand protonation states

    6. The catalytic endgame of photosynthetic water oxidation: operative S3 configuration, nature of the S4 intermediate, and the mechanism of O–O bond formation in photosystem II

    7. Experimental and theoretical validation of the proposed [O5O6]3−[O5O6]^{3-} (S=6S=6) S3-state species and the peroxo-superoxo route to O-O bond formation in photosystem II

    8. Proton-release routes and their coupling to electron transfer across the Kok cycle of Photosystem II water oxidation

    9. Ligand- or metal-centered oxidation in the final step of water oxidation in Photosystem II: the electronic structure of the S₄ transient and the mechanism of O–O bond formation at the Mn₄CaO₅ cluster

    The evolution of cooperative behavior3 questions

    1. Stability of the four routes to cooperation under realistic conditions: reciprocity dynamics with errors and limited rounds, punishment coevolution with countermeasures, and greenbeard persistence under recombination

    2. Generalizing the b/c>kb/c > k network-reciprocity rule for the evolution of cooperation on graphs beyond weak selection and large population size

    3. Robustness of dispersal-mediated intergroup cooperation: extending the Rodrigues–Barker–Robinson multi-group model to realistic spatial networks, conflict costs, discrimination mechanisms, resource landscapes, and cultural institutions

    How do the nuclear genome and extra-nuclear genomes coordinate?3 questions

    1. Identifying the genetic determinants of mitonuclear coadaptation among natural Saccharomyces cerevisiae isolates

    2. Retrograde signal and sensor machinery synchronizing chloroplastic and cytosolic protein synthesis across light/dark transitions

    3. Molecular mechanism of mitonuclear ratio homeostasis in mammalian cells: how nuclear ploidy and cell size are sensed to set mtDNA copy number, and the functional consequences of adaptive mtDNA copy-number increases

    Maintenance of mutualistic relationships1 questions

    1. Host sanctions and pollinator cheating in the fig tree–fig wasp mutualism: unresolved sanction precision, cues, and costs, and the heritability and fitness benefit of the pollen-free cheater phenotype

    Gene exchange in environmental microbial communities5 questions

    1. Functional distinctness and ecological contribution of phage-plasmids to the spread of accessory genes

    2. Clustering of horizontally transferred genetic material and the regulatory acceptance of transferred genes in natural microbial communities

    3. Do migration and horizontal gene transfer divide natural microbial genomes into multiple niches? Empirical validation and mechanism discrimination for the divided-genome model

    4. Molecular mechanisms and ecological determinants of horizontal gene transfer via natural competence in microbial communities

    5. Molecular mechanisms and causal determinants of horizontal gene transfer between distant bacterial taxa

    Can enzyme activity be tracked in real-time in living cells?2 questions

    1. The mechanistic origin of incomplete enzyme saturation in vivo and the generalization of intracellular kinetic formalisms for in vivo enzymology

    2. Quantitative calibration, fluorophore-pair and activity-architecture generality, temporal resolution, and microdomain distortion of FLINC/pcSOFI super-resolution imaging of live-cell biochemical activity

    What is the function of glial cells?3 questions

    1. Functional roles and transferred molecular cargo of long-range astrocyte gap-junctional networks in the mouse brain

    2. The physiological role of neuron-to-astrocyte Gq GPCR-mediated Ca2+^{2+} signaling: when, how, and whether astrocytes modulate neuronal circuits in the intact brain

    3. Mechanism by which adolescent oligodendrogenesis and myelin regulate inhibitory circuit maturation to limit neuronal plasticity in visual cortex

    Revealing the molecular genetic basis of intellectual disabilities3 questions

    1. Closing the diagnostic gap in severe intellectual disability: the non-exonic, mosaic, and oligogenic contributions to cases undiagnosed by exome sequencing

    2. Identifying the remaining molecular causes of unresolved X-linked intellectual disability families after comprehensive X-exome sequencing

    3. Completing the de novo mutation architecture of developmental disorders: undiscovered missense-driven genes and penetrance

    Analyzing the structure and function of neuronal ion channels1 questions

    1. Hydration states of selectivity-filter Na+ sites and the protonation-dependent binding of 4,9-anhydro-tetrodotoxin in the human NaV1.6 channel pore

    Metamorphosis of insects4 questions

    1. Mechanistic wiring of the prepupal state in the holometabolan metamorphic gene network: signals inducing the prepupal Kr-h1 pulse, stage-specific escape of Broad-Complex from Kr-h1 repression, and the cis-regulatory activation of E93

    2. Integrating developmental-genetic and adaptive explanations for the origin of the pupa in the evolution of complete metamorphosis in insects

    3. CtC-domain cofactors and the chromatin mechanism by which Krüppel homolog 1 represses E93 to mediate juvenile hormone's block on insect metamorphosis

    4. Causal validation of the MEKRE93 metamorphosis pathway in the mayfly Cloeon dipterum and the unresolved biology of the subimago stage

    Where do insect wings and flight ability come from?6 questions

    1. The dual-origin question for insect wings: tissue identities, history of the pre-wing gene network, and the merger of wing-homologous anlagen (open question of Clark-Hachtel and Tomoyasu, 2020)

    2. Direct force measurement and microstructural corrections in insect interfacial flight, and the evolutionary viability of surface skimming as a pathway to insect flight

    3. The evolutionary origin of insect wings: tergal, pleural, or dual origin of the winged-insect body plan

    4. The deep backbone and timescale of insect evolution: the Palaeoptera problem, the position of Psocodea, and the gap between molecular dates and the early fossil record

    5. Homology versus co-option of the Tribolium T1 wing serial homologs and the mechanism of dual-tissue merger in the evolutionary origin of insect wings

    6. Phylogenetic and developmental-genetic reconstruction of the exite-to-wing transformation in insect evolution

    Who were the ancestors of insects? Did they have wings?8 questions

    1. Tracing the exite-to-wing transformation: the evolutionary and developmental-genetic origin of insect wings from ancestral crustacean leg segments

    2. Critical experimental tests of the arthropod leg-segment alignment model: free-eighth-segment knockouts, the exite origin of myriapod tracheae, and the homologies of lateral outgrowths

    3. The sister group of Hexapoda: resolving the phylogenetic position of insects within Pancrustacea

    4. Unresolved deep nodes and early timescale of insect evolution: basal pterygote relationships, the placement of Psocodea, and the Ordovician origin of insects versus the Cambrian–Silurian fossil gap

    5. Timing, precursors, and ecological context of the origin of insect wings and flight

    6. Evolutionary origin and functioning of the pregenital abdominal outgrowths of the viviparous earwig Arixenia esau

    7. Cellular lineage contributions of tergal and pleural wing-serial-homolog tissues to the insect wing: resolving the spectrum of the dual-origin hypothesis

    8. Open questions from the mayfly genome: the evolutionary origin of insect wings and the genomic basis of mayflies' aquatic–aerial adaptations

    Are insects 'flying crustaceans'?5 questions

    1. Mechanistic basis, functional scope, and evolutionary origin of the springtail blastodermal cuticle as an egg-protection trait in hexapod terrestrialization

    2. Subcoxal origin of pleurites in myriapods and the homology of the insect subcoxa to crustacean proximal leg segments

    3. Unresolved questions on mushroom body homology and divergence across Pancrustacea: circuit organization in Brachyura, functional significance of the columnar-to-hemiellipsoid transformation, and the remipede conundrum

    4. Resolving the recalcitrant deep nodes of the pancrustacean phylogeny: the position of Copepoda within Allotriocarida, ostracod monophyly, stomatopod placement, and the Ediacaran-versus-Cambrian dating discordance

    5. Critical tests of the arthropod leg segment alignment model: functional, expression, and fossil validation of one-to-one leg-segment homology

    How is follicle formation and development regulated?4 questions

    1. Mechanism of ERV-mediated epigenetic priming of the ovarian reserve: what targets newly evolved retroviral regulatory elements for chromatin opening, and what releases the poised state at follicular activation

    2. Physiological extra-follicle control of primordial follicle activation: endogenous activating signals, their source cell types, and coupling to oocyte-intrinsic PI3K signaling in the intact ovary

    3. How ESR2 (estrogen receptor beta) maintains the primordial follicle reserve: direct versus indirect repression of pro-activation genes, cellular site of gatekeeping, and ligand-based manipulation of follicle dormancy

    4. Unresolved mechanistic facets of the oocyte-derived RSPO2/WNT–CTNNB1 paracrine axis driving early follicular growth

    Do ovoviviparity and temperature-dependent sex determination have evolutionary compatibility in reptiles?3 questions

    1. Do operational sex ratios drive facultative sex allocation in viviparous skinks with thermolabile sex determination? Cues, timing, thermal thresholds, and field operation

    2. Persistence and adaptive buffering of climate-driven offspring sex-ratio bias in the viviparous snow skink Carinascincus ocellatus

    3. Mechanism of the gestation-temperature sex-ratio bias in the viviparous lizard Eremias multiocellata: genotype-dependent embryo mortality, thermal sex reversal overriding ZZ/ZW genetic sex determination, or sexing artifact

    Why does the immune system produce a strong response to only a few protein antigen sequences (immunodominance)?2 questions

    1. Quantitative determinants and genome-scale prediction of immunodominance hierarchies for MHC class II-restricted CD4 T cell epitopes

    2. Determinants and controllable redirection of B cell immunodominance hierarchies to influenza virus hemagglutinin

    What is the exact biological significance and mechanism of immune cells entering and exiting tumor cells?1 questions

    1. Heterotypic cell-in-cell formation in pancreatic ductal adenocarcinoma: causal role in immune evasion and progression, mechanisms of immune-cell internalization, and clinical validation of the L/MiT biomarker

    How does sex change occur in certain animals?2 questions

    1. Functional validation of the socially cued sex-change cascade in the bluehead wrasse: cortisol trigger, brain-to-gonad signaling, neofunctionalized sex genes, and epigenetic reprogramming

    2. Unresolved biology of testicular-inducing steroidogenic (TIS) cells in grouper sex change: endocrine mechanisms in TIS-lacking lineages, TIS–Leydig lineage relationships, roles in socially controlled sex change, and TIS cell differentiation

    How does Deinococcus radiodurans withstand high doses of radiation?8 questions

    1. Molecular basis of growth-phase-dependent ionizing-radiation resistance in Deinococcus radiodurans R1: the 15-minute revival effect, missing stationary-phase regulation, and unexplained antioxidant determinants

    2. Activation pathway and population-level function of the MazEF-dr toxin–antitoxin module in Deinococcus radiodurans under DNA damage stress

    3. The DrRRA activation pathway in Deinococcus radiodurans: identifying the upstream sensor kinase for extreme radioresistance

    4. The uncharacterized LexA1/LexA2 regulon of Deinococcus radiodurans: direct targets and regulatory function of two RecA-cleavable LexA paralogs in a bacterium without classical SOS

    5. Functional and regulatory characterization of the expanded DdrO-controlled radiation/desiccation response (RDR) regulon of Deinococcus radiodurans

    6. Molecular mechanisms of guanine quadruplex DNA regulation of genome functions in the gamma-radiation response of Deinococcus radiodurans

    7. In vivo ligand identity, structure, and reactive-oxygen-species scavenging mechanism of the low-molecular-weight Mn2+–metabolite antioxidant complexes in Deinococcus radiodurans

    8. Molecular mechanism of ESDSA-mediated genome reassembly in heavily irradiated Deinococcus radiodurans: resection machinery, polymerase switching, synthesis-mode partition, and fragment-annealing coordination

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