Chemotherapy-induced senescence (TIS) is an alternative form of senescence, which is triggered by inhibiting the cell-cycle (senescence after growth arrest or SAGA) with CDK4/6 inhibitors, such as palbociclib. MacroH2As (a non-canonical histone variant of H2A) are enriched in during senescence and is believed to maintain heterochromatin and repression of cell cycle genes. The nucleosome-nucleosome interactions of macroH2A, which influence compaction and transcription, remains largely unknown. This is mainly due to the limitation of current techniques and the challenges which heterochromatin pose. However, the structural mechanisms of macroH2A and its subtypes (1.1, 1.2, and 2) play to maintain stable gene repression during senescence is largely unknown. Using a TIS model liposarcoma cell line and by developing chromatin targeted probes to induce spatially correlated breaks to infer structural information on the nanoscale (tri-nucleosome) level, I will investigate the structural-function relationship in heterochromatin and macroH2A in SAGA induced liposarcoma cells. The findings of this work will provide a better insight into this novel mode of senescence (TIS) by understanding how chromatin reorganization and cell growth genes are repressed and maintained by macroH2A.

Shigella is an important human pathogen responsible for 164,000 deaths per year, and cases of antimicrobial resistance are rising. In the lab, Shigella has emerged as a paradigm of cellular microbiology whose investigation has enabled landmark discoveries in infection and cell biology. Septins, a poorly understood component of the cytoskeleton recognised for their roles in cell division, can entrap cytosolic Shigella in cage-like structures for host defence. For cage entrapment, new work has shown that septins recognise micron-scale curvature presented by Shigella. Despite recent insights, the physical and molecular determinants of septin recruitment and cage assembly required for Shigella entrapment are mostly unknown. My proposal will investigate biophysical cues that underlie Shigella-septin interactions, and illuminate their role in cell-autonomous immunity. Using state-of-the-art fluorescence microscopy techniques, I will first investigate the spatial dynamics of Shigella virulence proteins and cell biophysics in broth culture and during septin cage entrapment in vitro using purified proteins. Next, I will resolve the impact of biophysical cues presented by Shigella which trigger cell-autonomous immunity during infection of human epithelial cells. Together, these integrative experiments will provide valuable insights about biophysical cues sensed by cell-autonomous immunity to defend against intracellular bacterial pathogens, bridging our views of biophysics and host defence. The outcomes of my research plan are expected to discover novel concepts in infection biology and cellular homeostasis, and may inspire septin-based approaches to counteract bacterial infection.

Cellular identity is defined by the expression of specific gene sets. Once established, the information to maintain gene expression programs is stored in alternative chromatin states, which are thought to be propagated through cell divisions to maintain cellular identity. However, although cellular memory is widely accepted as an important aspect underlying development, empirically it is yet to be demonstrated to exist at the single-cell level. Indeed, one possibility is that functional chromatin states are epigenetically propagated through mitosis, and a cellular memory operates at the single-cell level. Alternatively, cell fates could be inherently probabilistic, depending on the distribution of regulatory factors between nascent cells. In this project I propose to investigate this topic by combining advanced imaging, single-cell multi-omics and prospective lineage tracing. To study molecular states in cell pedigrees I will take separate approaches, using mouse embryonic stem cells as model. First, to test how much of the transcriptional identity of a parent is maintained in progenies, I will analyse transcriptional states of individual cells in traced lineages. Second, to understand if parental chromatin structures that underlie locus activity can be reproduced following mitosis, I will study similarities in locus conformation in related cells. Finally, I propose to investigate how transmission of molecular states changes upon lineage commitment, and in the absence of the epigenetic regulator, Polycomb. Altogether, this comprehensive study will uncover how developmentally important functional chromatin states are maintained through mitosis at the single-cell level.

Shoot branching in plants integrates a wide range of developmental and environmental cues. During shoot branching, axillary buds transition from dormancy to growth, regulated by signaling factors such as hormones and nutrients, which are produced, transported, and consumed in different ways across the plant. In many species, the highly conserved transcription factor BRANCHED1 (BRC1) maintains axillary buds in a dormant state. The hormone strigolactone (SL) increases BRC1 activity and promotes bud dormancy, and sucrose decreases BRC1 activity and releases bud dormancy, but their relative contributions remain unclear. To clarify mutual dependence of transport and gene regulation during shoot branching, I will determine: (1) how BRC1 activity and axillary bud dormancy depend on transport of SL, sucrose, and other signaling factors, and (2) whether transport of signaling factors into/out of axillary buds depends on plasmodesmata (PD) constituents and aquaporins regulated by BRC1. I will develop a new microfabricated device to enable dynamic buffer control, while live confocal imaging axillary bud activity and growth. I will image fluorescent reporters in existing and new Arabidopsis lines, and I will develop mathematical models integrating transport and gene regulation, to describe and predict dormancy-to-growth transitions in isolated and interacting axillary buds. Few models of plant development have integrated transport mechanics and gene regulation in this way, so this work will have more general implications for plant development.

Birds are extremely agile and robust flyers, able to cope with challenging gusty wind conditions and perform remarkable aerial manoeuvres. To do so, birds take advantage of the flexibility of their feathers, which vibrate as a function of airflow, stimulating the mechanosensory neurons in the skin, to provide information about the airflow over the wings. We aim to explore this complex sensorimotor loop, first to identify what aerodynamic information is available to birds to help control their flight and understand how birds’ wings can act both as aerodynamic surfaces and as a distributed airflow sensing array and then to understand how this aerodynamic information is encoded in the nervous system. Although airflow sensing is thought to be critical for efficient and agile flight, almost nothing is known about how changes in airflow translate to feather movement and subsequent neural signaling. Thus, this work addresses a broad biological question about sensory encoding of aerodynamic information. This proposal represents an integrated, international collaboration to explore this question across multiple levels of organization, from the movements of feathers to neural activity during perturbed flight manoeuvres. Dr Windsor (University of Bristol, UK) is an expert in using computational image analysis to study animal dynamics and his team will use techniques from aerospace engineering to look at the aerodynamic and vibrational properties of feathered wings, including measurements of the wing motions of behaving birds. Dr Perkel (University of Washington, Seattle, USA), an expert in songbird neuroscience, will investigate the physiological mechanisms underlying the encoding of this mechanosensory information by the nervous system. His lab will record electrical signals from single neurons in the wing nerve and spinal cord of zebra finches and trace their neural pathways. Dr Woolley (McGill University, Montreal, Canada) is an expert in behaviour and neurophysiology. Her lab will map the regions of the brain responding to airflow stimuli based on insights gained from Dr Windsor’s and Dr Perkel’s groups and then measure neural responses in flying birds. By combining approaches from aerospace engineering and neuroscience we aim to understand the functional properties of wing mechanosensing that allow birds to “feel” their way through the air.

Gene regulation is fundamental to almost all biological processes and is the critical driving force for the generation of the diversity of cell types that make up a multicellular organism. Yet, we still do not fully understand how gene expression is regulated and modulated with changing cellular contexts. Gene transcription occurs in a discontinuous manner, where bursts of RNA production are interspersed by periods of gene inactivity. As the major regulators of the initiation of transcription, enhancers have been reported to modulate transcriptional bursting. However, how this is achieved remains largely unexplored. Here, I will investigate how enhancers influence transcriptional bursting by finely tuning the nuclear concentrations of specific enhancer-binding transcription factors (TFs) in a very precise and dynamic manner. To manipulate TF levels, I will exploit an optogenetic system recently developed by the Furlong lab, which will allow me to address this question at an unprecedented quantitative and temporal resolution for the first time in a living embryo. The functional impact of manipulating TF concentration on bursting will be quantified at two levels using state-of-the-art approaches. First, globally, using a spatial single-cell and single-molecule genomics method (intronic seqFISH+) to identify general regulatory principles. Second, dynamically, using live imaging and the MS2 and PP7 systems to dissect how burst frequency, duration and intensity are mediated by enhancers. Together, these findings will advance our understanding of gene regulation by providing new insights into the kinetics, regulation and general robustness of transcriptional bursting.

Protein post-translational modification (PTM) is a sophisticated form of cellular information processing, essential for the emergence of organismal complexity, such as the evolutionary expansion of the cerebral cortex. Nonetheless, it is unclear how PTMs shape brain development and understanding the interconnections between these two highly complex mechanisms may open a ground-breaking avenue for tackling neurological disorders. The host lab demonstrated that protein AMPylation and the ER-specific AMPylator FICD are enriched in the neuronal niche and that FICD-mediated protein AMPylation is critical to neuronal differentiation. However, a set of the identified AMPylated proteins in neurons is enriched in proteins with mitochondrial localization, hinting that the mitochondrial-specific AMPylator SelO has an important role in neuronal mediated AMPylation and plays a critical role in neuronal metabolism and metabolic disorders. I plan to elucidate the role of the uncharacterized mitochondrial SelO using state of the art proteomic approaches in human cerebral organoids and decipher the SelO-Dependent AMPylome. I will dissect the role of SelO-dependent AMPylation in neuronal development, using a novel live imaging technique to track AMPylated proteins in mouse cortical development and human cerebral organoids. In addition, I will investigate the role of SelO in mitochondrial and cellular metabolism, using the candidates identified in the SelO-dependent AMPylome. Overall, I aim to elucidate the role of protein AMPylation in the metabolic regulation of neurogenesis, and its importance in Mitochondrial Disease and Autism Spectrum Disorders.

Living matter represents spatially structured soft materials with internal energies far from the thermal equilibrium. The inherent order and fluidity in such systems lead to dynamic, anisotropic properties spanning orders of scales. Spontaneous symmetry breaking in structured matter nucleates local singularities called topological defects. Despite reported evidence of topological defects in living systems, their biological functions have remained grossly unexplored, denying us, to date, a holistic biophysical picture. With a focus on microbial species, I propose to develop the first experimental framework to understand topology-induced microbial physiology, based on a combination of cutting-edge methods including advanced imaging, spectroscopy and machine learning. Specifically, by tracking defect genesis and dynamics in bacterial colonies of species with diverse phenotypes (morphology and motility traits), I will quantify biological activity in the defect vicinity over short to generational timescales. Using fluorescence confocal and electron microscopy (to track molecular transport, exudates and ROS levels), and nanoSIMS technique (to quantify nutrient uptake), I will obtain seminal data linking defects to microbial physiology, and harness this mapping relation to construct machine learning algorithms that will ultimately predict the biological role of defects in multi-species communities. By discerning the biological functions of topological defects, I will be in robust position to pioneer a quantitative approach to this uncharted problem, heralding a unifying framework to predict more complex scenarios, thereby advancing our general understanding of physics of life.

The small intestine is the major site of nutrient absorption after food intake and malabsorption (impaired nutrient uptake) affects millions of people worldwide. However, there is an unmet need to study malabsorption with physiologically relevant in vitro models. Glucose-galactose malabsorption (GGM) is a genetic disorder that affects the SGLT1 protein, which results in diarrhea and life-threatening dehydration upon glucose and galactose consumption. In my research I aim to establish a physiologically relevant platform to assess nutrient bioavailability employing intestinal organoids (biovanoids) to model GGM. GGM biovanoids will be generated by introducing a disease-associated mutation in SGLT1 (C292Y) using CRISPR/Cas9-mediated base editing. Some aged GGM patients describe an acquired glucose tolerance, which accelerated upon probiotic consumption of certain bacteria. The influence of SGLT1 mutations on host-microbe interactions and possible metabolic adaptation through e.g. age-associated hormonal changes will be studied using GGM biovanoids. This may offer an opportunity to introduce glucose tolerance in young GGM patients. Overall, biovanoids offer a promising platform to generate essential knowledge about malabsorption. To elaborate further applications, biovanoids will be validated for their potential to predict intestinal absorption and gut wall metabolism of drugs. Poor bioavailability contributes to high attrition rates of oral drugs during clinical phases of drug development and currently applied models fail to reliably predict bioavailability in humans. Biovanoids could improve these predictions to eventually increase successful drug approval to the market.

A high level of oxygen in the atmosphere is taken for granted as it is indispensable for human and most animal life. Yet, life (bacteria and unicellular eukaryotes) evolved for over 2 billion years in a low oxygen environment. Oxygen became widely available only in the last 600 million years and was likely the main factor behind the rapid diversification of most complex multicellular life forms. For elaborate multicellular tissues to form, their overall shapes however must still satisfy oxygen demands of individual cells. Oxygen consumption will rapidly reduce the oxygen level within a few cell depth into the tissue. This becomes a problem in early embryonic development before respiratory and circulatory systems are established. Many cells still need to differentiate and migrate for long distances and place themselves at the right destination. It is largely unknown what makes the varying oxygen environment and the execution of their precise differentiation and navigation within a tissue compatible. The project aims at elucidating the common basis of oxygen dependency in morphogenesis by studying how the social amoeba Dictyostelium detects and reacts to oxygen at the molecular level and how this dictates cell migration and morphogenesis. Dictyostelium is an organism evolutionarily close to the branches of multicellular evolution, and presents enormous advantages to be easily cultured in the laboratory and reversibly switched from unicellular to multicellular states in less than a day. Amoeboid cells are able to change their state (by differentiation) and place themselves in more favorable conditions for foraging and respiration (by migration). An emphasis is placed on clarifying this most fundamental and primordial characteristic with a focus on the cross-scale quantitative relationship between oxygen, metabolic states, cytoskeletal machineries and migratory modes. New screening methods based on aerotaxis responses, oxygen sensors and 3D microscopy will be combined with molecular genetics of oxygen response pathways. The role of the new mechanism unearthed will further be tested for their roles in neural crest cell migration in zebrafish. They will be formulated into multi-scale mathematical models to clarify how the coupling between oxygen consumption, sensing and migration of individual cells gives rise to robust and collective morphogenetic movements.

The skin epithelium forms a primary barrier against inflammation-inducing environmental agents and is maintained by the epithelial stem and progenitor cells (EpSCs). Stem and progenitor-cells (SCs) adapt to various conditions via crosstalk with their local microenvironment or "niche". The EpSC niche is comprised of fibroblast, neuronal, immune, and other cells that provide context-specific signals to direct SC function. However, how the EpSC niche is affected by inflammation is poorly understood. In addition to actively participating in inflammation, EpSCs also retain a memory of inflammation long thereafter, which enables more rapid responses to subsequent assaults. However, the contribution of niche factors to maintaining EpSC memory is entirely unknown. To address this knowledge gap, I propose to systematically chart the cellular constituents of the EpSC niche before, during, and after acute inflammation. Armed with this high-resolution map of the EpSC niche, I will then perform functional studies to identify niche factors that control EpSC inflammatory function and memory. Understanding inflammation-induced niche rewiring and identifying the key inflammatory niche regulators of EpSCs may illuminate mechanisms of inflammatory epithelial pathologies such as psoriasis, chronic non-healing wounds, and cancers that are rooted in SC dysfunction.

The world around us is constantly changing – new elements appear all the time. How does the brain decide what novel things to explore? Animals exist in a constant push and pull between being adventurous and conservative. My objective is to understand how the brain controls the behavioral response to novel stimuli under naturalistic settings, and how those brain functions have been modified by evolution and ecology. During my fellowship I will approach the neurobiology of novelty from an interdisciplinary perspective that merges the evolution of behavior with its neurophysiology. I chose an ideal model system to study comparative neurophysiology: the deer mouse (genus Peromyscus). Deer mice are the most abundant mammal in North America (comprised of >50 species). Different Peromyscus species have evolved distinct behavioral repertoires. I will combine evolution and ecology with novel tools such as fiber photometry and wireless electrophysiological recording to understand the computations performed in the deer mouse brain under ethological conditions in response to novel stimuli. Specifically, I will study the brain of a variety of Peromyscus species with distinct behaviors under different novelty challenges. Overall, I will focus my research program on testing three general hypotheses: (i) different species or populations of Peromyscus will present differential response to novel objects, and (ii) dopaminergic neurons projecting to the tail of the striatum, controlling novelty responses behave differently in these species (iii) dopaminergic neurons projecting to the tail of the striatum shape neophobic behaviors in the wild.

Gene regulatory networks (GRNs) represent the wiring diagrams of cells and can be envisioned as the blueprint for organism development. Transient interactions of transcription factors (TFs) and DNA as well as chromatin structure fine tune gene expression and allow cells with the same genome to give rise to a myriad of cell types and tissues. My overall-goal is to elucidate this fundamental process live and investigate, how exactly transient interactions, dynamics, and variations in absolute concentrations of TFs on the molecular level shape GRNs, impact on vertebrate embryo development, and can be used to infer cellular identity. Our current understanding of gene regulation arises mostly from static measurements employing sequencing technologies and in situ hybridisation approaches. However, extracting quantitative clues such as TF concentrations and their changes over time is very challenging yet crucial to shed light on the organising principles. I propose to use quantitative imaging, fluorescence fluctuation spectroscopy (FFS), and endogenous labelling of TFs to measure absolute, native concentrations and interaction dynamics directly during live zebrafish development. Using these readouts as a new handle on cellular heterogeneity, I will elucidate how specific TFs regulate hindbrain establishment and by employing engineered TFs as reporters for DNA accessibility, how overall chromatin organisation evolves in different developmental contexts. Together with the design of an open-source microscopy-spectroscopy platform tailored for in vivo FFS, this project will result in previously unattainable, quantitative insights into vertebrate embryogenesis.

Symmetry breaking is a process during which a homogeneous system adopts asymmetry and is fundamental during initial cell fate determination in early development and regeneration. Single-cell interactions and information exchange with the environment allows for such large-scale coordinated behaviors. Identifying mechanisms driving symmetry breaking is not trivial due to frequent nonlinear relationships between the system’s lower- and higher-order dynamics. Employing approaches from cell-, systems- and biophysical fields, I will study symmetry breaking in intestinal organoids. In a uniform growth-promoting environment, only a subset of intestinal stem cells differentiates into secretory cells. Recent evidence implicates an upstream regulatory pathway of extracellular signal-regulated kinase (ERK) in contributing to proper patterning of the stem cell niche. The proposed research aims at understanding whether and how ERK mediates symmetry breaking during intestinal organoid formation. To address this fundamental question, I will: 1) analyze the spatiotemporal-specific role of ERK signaling during symmetry breaking, 2) identify ERK-mediated tissue-level coordination focusing on biochemical and mechanical regulation, 3) determine how single-cell interactions are integrated into large-scale collective behaviors using theoretical modeling and optogenetics. This research project will determine the spatiotemporal-specific role of ERK during symmetry breaking with unprecedented multiscale resolution and provide key insights into the emergence of complexity and collective behavior fundamental to processes such as mammalian development, cancer invasion and wound healing.

Cardiovascular disease (CVD) is the leading cause of global morbidity and mortality. While psychological stress is a known cardiovascular risk factor, the mechanism by which the brain translates stress into CVD is poorly understood. The underlying cause of CVD is a chronic inflammatory disease called atherosclerosis, the progression and exacerbation of which have been strongly associated with the immune system, including B cells. B cells perform many functions including production of antibodies that provide immunity against disease and cytokines that modulate leukocyte function. However, it remains unknown whether B cells mediate the effects of stress on CVD. Recent studies from the host lab show that stress profoundly affects the number and distribution of B cells in the body. This occurs via a mechanism dependent on the activation of the hypothalamic-pituitary-adrenal axis. In this proposal, I will test the hypothesis that stress aggravates atherosclerosis by modulating B cell function. To recapitulate stress, I will employ a combination of optogenetic and chemogenetic approaches available in the host lab to locally activate specific regions in the brain and characterize the subsequent impact on the phenotype and functional diversity of B cells. I will then identify the B cell-specific mechanisms that mediate the effects of stress on the progression of CVD. These studies will not only delineate potential therapeutic targets for immunomodulation of B cells in prevention and treatment of atherosclerotic CVD, but also provide a direct mechanistic link between stress and chronic inflammation, a general concept with implications beyond atherosclerosis.

The flow of information between different regions of the brain during decision making is a largely unknown process. This is mainly because there are no tools available to disentangle the complex interaction of myriad cell types in the brain, governed by gene expression, connectivity, spatial organization, and other properties. This proposal aims to investigate the anatomical substrate of inter-regional communication at single neuron level. We hypothesize that a specific group of neurons that project directly between brain areas provide the “scaffolding” for the correlation between structural and functional connectivity. Tools developed in the proposed host group, as well as their previous work on the topic, make this question accessible for investigation. We aim to identify this privileged subpopulation of neurons by combining two-photon imaging of activity in single neurons with anatomical projections extracted using Barcoded Anatomy Resolved by Sequencing (BARseq). Successful completion of this project would generate unprecedented datasets that bridge information at all levels–anatomical, genetic, physiological and behavioural. Gaining knowledge of the flow of information in the brain would push the frontiers of what it is one of the grand challenges of our time–to understand how behaviour arises from neural circuits.

With their multiple arms, three hearts, suckered tentacles, camera eyes, and fast colour-changing skin, cephalopods seem to come from an imaginary world. These iconic invertebrates play a major role in balancing the entire marine ecosystem, yet the 4 million metric tons caught annually have led to their global decrease. Cephalopod diet and feeding systems remain enigmatic. They have a ‘beak’ composed of two jaws with no direct contact, a radula, and specialised masticatory muscles. Unravelling the secrets of their feeding system can inform us about their diet and potentially have huge global impact by aiding their survival. In this project, I will bring together for the first-time expertise in cephalopod biology and biomechanics to quantitatively characterize the anatomy and function of the feeding system in different species representing all cephalopod families. I will use a range of techniques based on material characterization and computational modelling to test 4 hypotheses. I will investigate the (1) material content and mechanical properties of the jaws and correlate these with their bite force and diet; (2) shape and surface properties of cephalopod jaws and its potential correlation with their diet; (3) muscular jaw articulation of cephalopods and the mechanisms that control its motion considering a range of diet; (4) impact of overall jaw and muscular joint morphology on the level of mechanical strain across each component. A major part of cephalopod biology will be unravelled in this project, providing new foundations for cephalopod conservation and other areas such as bioinspired soft robotics.

The role of metabolism during developmental processes remains largely unexplored due to challenges in measuring spatiotemporal dynamics of metabolic activities. In the mammalian post-implantation embryo, pluripotent cells differentiate into three germ layers, the ectoderm, mesoderm and endoderm that undergo specific morphogenetic movements during a process known as gastrulation. While it is known that metabolites influence cell fate by modifying the epigenetic and transcriptional states, the question, whether metabolism plays a functional role in germ layer specification, has not been addressed in an in vivo context. The two main aims of the proposed project are to characterize the metabolic profiles that accompany the emergence of germ layers and their possible function during germ layer segregation i.e. symmetry breaking that establishes the primary body axis. To accomplish both aims, I will use gastruloids, aggregates of embryonic stem cells that recapitulate hallmarks of gastrulation, as a model system. The gastruloid system will allow me to combine metabolic measurements, live imaging of biosensors and metabolic state reconstruction, to uncover emerging differences in metabolism among cells of the different germ layers. Further specific manipulations with inhibitors and optogenetic tools will test if the activity of certain metabolic pathways regulates cell fate decisions and coordinates tissue scale cell movements and thus probe possible molecular mechanisms. The findings of this project will reveal fundamental mechanisms underlying the interplay between metabolism and cell fate determination and thereby change our view of how gastrulation is robustly regulated.

Broadcast spawning is a method of reproduction used by many species of coral, where the corals release their gametes in a perfectly timed, synchronous manner to maximise fertilisation. The timing and molecular mechanism behind this extraordinary event are not understood. Coral bleaching and the death of reefs is something that is now firmly anchored in the public consciousness. However, another threat is looming for coral, the asynchrony of spawning. This marginalised ecosystem now faces an even bigger threat, the possibility of not being able to reproduce, spelling disaster not just for marine life, but also for the communities that depend on them. An understanding of this asynchrony is key and I have therefore designed a research plan which examines the molecular mechanisms behind the spawning event. In particular, I aim to study the light biology of coral, as they use multiple light stimuli, including moonlight, to regulate reproduction. To this day, we do not know what photopigments corals employ, where these are located and whether the algal symbiont is key in initiating different spawning steps. Moonlight is the critical signal, however, the full moon is present every 29 days, so another gating mechanism must exist. I aim to find out exactly what this is by varying different parameters in a lab setting. Using temporal differential gene expression analysis around this critical moonlight signal will provide a basis for understanding the key cellular responses driving spawning. Pioneering a deep understanding of reproductive asynchrony will allow the implementation of improved conservation measures and help save the world’s reefs from destruction.

The group setting forms the basis for most social interactions. However, despite the importance of group social behavior in almost every aspect of animal’s lives, very little is known about its neuronal substrates. This can be attributed to challenges associated with reductionist approaches to capture the complexity of group social interactions. Thus, a paradigm shift is necessary. Specifically, we identify these major gaps where most studies have: (1)focused on one brain at a time, (2)often did not consider individual differences and (3)neglected the long-term dynamics of group social behavior, especially in the natural context. To overcome these gaps, I propose an approach that leverages the rich social interactions in groups of bats, a new animal model for group social interactions in neuroscience. Utilizing cutting-edge methodologies that enable simultaneous wireless recording and manipulating of neural activity across the brains of group members, I will study the neural mechanisms of group social interactions as these naturally unfold. I will begin by focusing on two core aspects of group social interaction and their manifestation in the frontal cortex of socializing bats: (1)neuronal representations of individual’s identity as related to social vocal communication, (2)interbrain coupling across group members. Thus, I will study the relationship between group social and neural dynamics extending from the single neuron level in the individual brain to the relationship in neural dynamics across the brains of group members. Combined, this project will allow, for the first time, a unique mapping of the group social network onto the neuronal network of its members.