Identical genomes in social insects generate castes with distinct morphologies and behaviors. The Harpegnathos ants have a remarkable lifestyle, whereby the queen’s death triggers transition of a subset of workers to become her substitutes, called gamergates. This entails minor changes in morphology, yet a pronounced shift in behavior, and remarkably, a fivefold extension of lifespan. This process is reversible if the gamergate is placed in a colony with a real queen. The capability of such a dramatic transition in adult life provides a unique context to study neuronal plasticity and aging. Moreover, social insects challenge major aging theories as their calorie intake and fecundity positively correlate with lifespan, in contrast to most animals. I aim to provide an extensive mechanistic description of the worker-to-gamergate transition in H. saltator, and to characterize the mechanisms of the resultant aging deceleration. I will study the brain as it regulates caste transition and produces hormones implicated in aging, while also being affected by both processes. First, I will perform single-cell RNA-sequencing of the worker and nascent gamergate brains to describe changes in genes controlling synaptic wiring and cellular signaling. Next, I will test whether deceleration of aging in gamergates is accompanied by decreased rates of molecular damage, protein synthesis, transposon activity, and telomere shortening. Finally, I will combine both datasets to link transcriptional changes during the caste transition with aging-related molecular processes. Deciphering the paradoxical aging mechanism in social insects may uncover previously unknown strategies to prolong lifespan.

Glycerophospholipids are one of the major lipid species in cellular membranes of eukaryotic cells. Among glycerophospholipids, phosphatidylethanolamine (PE) is a highly conserved lipid, found in all organelles but mainly synthesized in the endoplasmic reticulum (ER) and in mitochondria. If it has been shown to play essential roles in membrane protein structure and function, its distribution and metabolism have not been fully elucidated. Indeed, little is known about lipid transport in terms of quantitative and qualitative contribution of each pathway, because methods to measure lipid transport between organelles in cells are lacking. Unlike proteins which are relatively easily manipulated by genetic techniques, individual lipid species cannot be readily modified in vivo. Here, I propose to develop and use chemical tools to study PE transport and metabolism in living cells with high spatiotemporal resolution. I will synthesize photocaged PE which can be localized with precision to mitochondria (or ER) within cells and then released with irradiation of light. Using isotope-labelling, I will trace their transport and quantify the metabolites inside living cells by lipidomics and mass spectrometry approaches. Moreover, mass spectrometry imaging could allow visualizing the de novo labeled phospholipids. This interdisciplinary approach will give us the spatiotemporal resolution that is needed to create for the first time a 4D map of PE metabolism in cells. It will allow us to elucidate its metabolism related to its dependence on intracellular localization and prove that PE can or cannot be transported, for instance, bidirectionally between ER and mitochondria.

Touch the sensitive plant Mimosa pudica and it rapidly changes shape, folding its leaves to deter herbivory and dislodge pests. This and other feats of rapid plant motion have fascinated scientists for centuries, but the physiological mechanisms underlying them remain poorly understood. I propose a collaborative, interdisciplinary project to elucidate two key aspects of rapid plant motion: sensation of mechanical stimuli and rapid generation of force. I hypothesize that knowledge of the sensory and motor strategies of motile animals can inform our approach to the study of rapid plant motion, and outline a novel experimental approach that draws tools and theory from the fields of biomechanics, neurophysiology, and materials science to explore rapid motion in Mimosa pudica, a model system for the study of rapid plant movement. I have identified an ideal host laboratory in which to carry out this work situated at a nexus of expertise in mechanotransduction, plant physiology, and mechanical modeling. To this environment I will bring expertise in skeletal muscle physiology and the biomechanics of force production. The proposed work forges a connection between seemingly disparate areas of physiological research, will provide unique training that increases my technical and theoretical breadth, and has great potential to elucidate basic principles underlying sensory and motor strategies in biological systems.

Protein degradation systems maintain protein homeostasis. A failure of these systems causes various diseases, such as neurodegenerative diseases and cancers. In eukaryotic cells, ubiquitin is a general marker for selective degradation and determines protein lifetime in vivo. In selective degradation, E3 ubiquitin ligases determine target proteins. Although there are ~800 E3 ligases in human, only a handful of them have already shown to recognize specific short peptide motifs called “degrons”. Moreover, the feature(s) for unstable or misfolded structures recognized by E3 ligases remain unclear. In part, this is because we lack a comprehensive approach to investigate the global relationship between protein structural stability, ubiquitination status, and lifetime of the protein. To reveal the effect of protein folding stability (and other features) on ubiquitination and biological lifetime in vivo, I propose to measure these parameters for thousands of designed mini-proteins, whose folding stability has been previously characterized in detail. First, I will measure biological lifetime for these mini-proteins by flow cytometry, and monitor their ubiquitination status by using top-down proteomics approach. Then, I will analyze these data by using in silico analysis and decipher what factor(s) determine ubiquitination states and biological lifetime. This highly innovative and comprehensive approach using thousands of designed proteins will allow me to uncover the fundamental principle for protein lifetime in vivo and provide a mechanistic basis for designing better tools to manipulate protein lifetime.

During gastrulation, embryonic stem cells are primed towards three germ layers: the ectoderm, the mesoderm and the endoderm. While acquiring their fate, the cells re-arrange massively and the embryo polarizes with the appearance of an antero-posterior axis. The signals that are necessary for this patterning and the role of the mechanical forces remain poorly understood, in particular for the human embryo. Synthetic biology has thus developed new models of embryos using human stem cell lines (hESCs). We propose to study the effect of differential mechanical tension on the appearance of a primitive streak in a synthetic human embryo. We will investigate the relationship between the WNT pathway activation and mechanical instability, following recent results on a biomechanical regulation of this pathway. We will first work on the correlation between the substrate induced curvature and WNT expression in 2D cultures of human stem cells. Secondly, we will map the resulting stress field of the cells to this expression pattern. Thirdly, we will study cellular self-organization under mechanical load in a 3D model synthetic embryo. We will eventually focus on the inducer role of a second cell population in the polarization of this synthetic embryo. In the four cases we will correlate the resulting dynamic features with the expression of markers relative to the three germ layers. We hope to provide a first quantitative understanding of the relationship between the force field and the differentiation of stem cells in a model synthetic embryo. This project will be co-supervised by Dr. Eric Siggia and Dr. Ali Brivanlou. The experiments will be performed in the Brivanlou lab.

Metabolic transformation is a key characteristic of cancer cells and considered a promising avenue for therapeutic intervention. Nevertheless, metabolic lethalities identified in laboratories often fail to translate to the clinic. This may be because the complexities of tumor metabolism cannot be recapitulated by studying cancer cell autonomous metabolism alone: tumors are not solid masses of cancer cells, but include host tissue, stroma, and immune cells that together shape the tumor metabolic environment. This insight highlights the need to observe and interrogate tumor metabolism in vivo. Metabolic studies rely heavily on mass spectrometry-based analysis of metabolites extracted from cells or tissues, but this approach lacks spatial resolution to resolve metabolic heterogeneity between cells. To address this unmet need, I will develop a transformative platform for single-cell tissue metabolomics using mass spectrometry imaging and use it to study redox metabolism in liver metastatic cancer to investigate a major unanswered question in cancer research: how does the host tissue support metastatic tumor growth? This work contributes a new strategy to incorporate spatial resolution into metabolomics and provides the first comprehensive analysis of the metabolic symbiosis between host and cancer cells in vivo. It aims to redefine the traditional approach to metabolic studies that can progress our understanding of metabolic heterogeneity. Focusing on liver metastatic cancer, I aim to provide novel mechanistic understanding of redox-metabolic crosstalk between cells in the tumor-host niche and explore strategies to interfere with redox metabolism to combat metastasis.

Living organisms constantly make important decisions in their dynamic environments in order to survive. Animals make effective decisions in response to sensory stimuli by recruiting both innate and learned information in their nervous systems, thereby guiding them to approach or avoid cues that are appetitive or aversive respectively. Importantly, in order to adapt to a changing environment, animals also need to update their memories over time. Understanding how the nervous system invokes previously stored information to dictate future decisions has been a central and historical goal in neuroscience. Recently, significant progress has been made in identifying the connectivity and functionality of specific circuits involved in distinct aspects of learning and memory. However, a challenging task has been to obtain a comprehensive and systems-level understanding of neural circuit dynamics by which memories are retained, extinguished or expanded and integrated with innate information to eventually drive various behavioural actions. In this proposal I aim to address this problem by using a novel setup to record the activities of multiple individual neurons that function at different levels downstream of the learning and memory centre in the insect brain in freely behaving animals subject to specific tasks over time. Importantly, by combining this data with synaptic-level circuit maps generated by electron microscopy, mathematical modelling to produce reliable circuit motifs, and precise optogenetic manipulations to test the models in vivo, we will obtain both a global and high-resolution understanding of memory-based and context-dependent action-selection.

Epigenetic modifications regulate development. In particular, genome-wide DNA methylation patterns undergo dynamic changes at cornerstones of mammalian development. While DNA methylation is essential for normal embryogenesis, how it regulates and maintains cell fate and function in vivo remains unclear. A key methylation-regulated developmental process is parental imprinting and perturbations to methylation imprints result in embryonic lethality. We discovered that paternal deletion of an essential imprinting control region in mammals results in a temporal-specific compensatory methylation switch onto the opposite maternal allele, minimising detrimental developmental defects. This suggests a novel paradigm of epigenetic plasticity with wider implications for the epigenetic control of genome function. Here, we will utilize cutting-edge DNA and RNA single-cell sequencing methods and in vivo knockout models to study the functional roles of parental-origin specific epigenetic plasticity during development. We will determine whether loss of imprinting drives compensating changes on the other allele and decipher the associated mechanism of regulation, maintenance and hierarchical interactions. We will investigate the genome-wide plasticity of imprinting by relating imprinted gene dosage dynamics with developmental time points and tissue expression, with specific focus on particular developmental niches. Our approach will elucidate a new avenue of epigenetic control during development and disease, contribute to our understanding of the evolution and flexibility of imprinting and provide novel insights into regenerative medicine, reproduction and epigenetic inheritance.

Sleep is widely acknowledged to be essential to brain function, including learning and memory. Although learning relies on synaptic plasticity, there is surprisingly no consensus on the nature and function of the synaptic changes sleep would mediate. The controversy in the field partly derives from the complexity of sleep structure, as sleep is composed of REM and non-REM stages suggested to hold different functions that are poorly investigated at the synaptic level. To address this issue, I propose to use a recently-developed 3D two-photon microscope in order to continuous monitor synaptic changes during learning and specific sleep stages. The mechanisms underlying sleep stage-dependent synaptic plasticity will be further investigated by combining Ca2+ imaging, light-induced CaMKII inhibitor and optogenetics. The data obtained will provide new insights into the role of sleep in synaptic plasticity, and might further reveal fundamental mechanism underlying learning and memory.

The regeneration of the adult skeletal muscle relies on the activity of resident muscle stem cells (satellite cells). These PAX7-positive (PAX7+) cells are predominantly quiescent in uninjured muscles, while being able to rapidly proliferate upon injury. Mouse satellite cells are known to be heterogeneous, with subpopulations exhibiting graded quiescent states and variable regenerative potential. However, the molecular identities and developmental trajectories of satellite cell subsets are not well established. Moreover, due to the limited access to human tissues, little is known about the biology of human PAX7+ cells. The host laboratory has recently developed robust differentiation protocols that enable efficient generation of myofibers and PAX7+ cells from pluripotent stem cells in vitro. In this project, I plan to use single-cell transcriptomics to chart the dynamic cellular landscape of human in vitro myogenic differentiation, as well as mouse muscle development in vivo, with the aim of revealing the identities of emerging cells during myogenesis, developmental roadmap for cellular heterogeneity and molecular signatures of quiescence. In addition, preliminary results implicate the retinoic acid (RA) signaling in controlling satellite cell quiescence. Assisted by single-cell profiling, the role of RA will be characterized in detail. To further uncover in an unbiased fashion the gene networks linked to quiescence, I will also conduct functional genomic screens based on the in vitro platform. Overall, this study will use diverse techniques and model systems to provide new insights into muscle stem cell biology and potentially benefit the treatment for muscle diseases.

Phenotypic evolution concurs with spatial and temporal gene expression changes. Most work have been focused on spatial gene expression variations, yet little has been known about whether the temporal alteration of gene expression, termed heterochrony, also contributes to morphological variations. In this proposed work, I aim to address this question using forelimb (FL) and hindlimb (HL) development in the mouse embryo as a model, due to the ease of experimental manipulation of this system. Although gene regulatory network underlying limb development is highly conserved, the morphology of FL and HL differs. An important distinction in their development is the relative duration of gene expression time – nearly all limb regulators express for a shorter period in HL, correlates with its curtailed differentiation time-scale comparing to FL. Whether and to what extent do such temporal gene expression differences relate to morphological divergence remains unclear. To this end, I will systematically and quantitatively characterize the kinetics of key limb regulators’ expression during the FL and HL development in the mouse embryo; then combining in vitro culture assays and sequencing methods to investigate the mechanisms causing temporal gene expression differences between the two appendages; finally, I will functionally assess the role of such heterochrony to limb morphology by altering the gene expression timing, first experimentally, in mouse and chick embryos; and then theoretically, by using mathematical modelling. Together, this proposed work can advance our understanding of the connection from genotype to phenotype and will also aid biomedical research on limb defects.

Keen observers of nature have often wondered why diverse species seem to behave similarly. For example, different species of Hawaiian spiders spin similar web architectures, diverse anoles lizard species bob their heads with the same styles and speeds, and distinct species of damselflies avoid predators using the same techniques. These and many other striking examples are thought to represent the convergent evolution of behaviors. Does this convergence reflect changes in the same genes or does evolution act through many genetic routes to create the same behaviors? Genetic differences clearly play a role in behavioral variation, but it remains challenging to identify the genes that underlie evolution of behaviors. However, convergence in the genetic basis of developmental or physiological traits has been discovered with many specific examples of genes and mechanisms, so it is possible to use studies of convergence to discover how behaviors evolve. Therefore, we will use a powerful comparative system to discover the genes and molecular mechanisms that underlie convergent evolution of behaviors for the first time across divergent animals.
The Caenorhabditis nematodes offer a unique experimental platform to connect behavioral differences to genetic differences. Starting with the keystone model organism, C. elegans, and existing data, we will characterize and classify genetic differences across wild isolates from three species of Caenorhabditis - C. briggsae, C. elegans, and C. tropicalis. Whole-genome genotype data combined with high-throughput, high-content imaging of behaviors from these same wild isolates will be input into unsupervised machine learning algorithms to create a high-resolution genotype-phenotype map for a range of natural behaviors and examples of convergence. This map will be queried for signatures of shared genetic changes at orthologous genes to identify which variants are most important evolutionarily. The result will provide the first systematic glimpse into the genomic “knobs” that control behaviors at single-variant resolution across species and insights into the repeatability of the evolution of behaviors.

Sea urchins are marine animals genetically close to the vertebrate lineage. Being eye-less and lacking a central nervous system (NS), these animals instead feature dermal photoreceptors dispersed over their spherical body surface and feeding into a decentralized NS. However, sea urchins can visually resolve objects and move towards them, and they can detect looming visual stimuli from any direction and accurately point their spines towards them. Such performance is normally associated with proper eyes feeding information into a brain. Sea urchins thus offer access to a unique visual system of a type that to date has not been studied in terms of its information processing. This alternative solution to vision may also have potential biomimetic applications for robotic miniaturization, smart probes, and intelligent materials where dispersed light detectors control the properties of the material.
The core of the proposed project is to investigate and model the neural mechanisms of information processing, which enables sea urchins to perform spherical vision by deploying an obviously very different mechanism from today's technology, and also very different from visually guided behavior in most other animals. Our study includes molecular and morphological identification of cell types, measurements of behavioral responses and electrophysiological photoreceptor responses, mapping the connectome of sea urchin photoreceptors and NS, and theoretical modelling of the information processing underlying visually guided behavior. We will map the connectomics of the NS and record the activity from key positions in the processing of visual information and generation of locomotory responses. The data will be used for computational modelling of the entire process from visual input to motor control. Special focus will be given to behavioral decisions where small changes in stimuli cause behavioral switches. We will also use genetic approaches to test the agreement between theoretical models and actual behavior.

The Personalized, Regenerative Medicine of the future will rely on being able to make replacement cells and tissues of choice at will and in a robust, predictive manner. However, key challenges have to be overcome before the promise of personalized stem cell therapeutics becomes a reality. This is because stem cell renewal/differentiation are stochastic processes, precluding the differentiation of a stem cell population into a homogeneously differentiated desired cell type, but also leading to spurious differentiation during renewal. This is thought to partly arise from heterogeneous single-cell signaling states among different cells of a population, which are not measurable using classical ‘population-average’ biochemical methods. A mechanistic understanding of how dynamic signaling processes control differentiation/renewal fates at the single-cell level might therefore significantly improve our capacity to robustly and precisely manipulate cell fates for tissue engineering purposes. We propose to use an integrated interdisciplinary strategy to map the dynamic, single-cell signaling programs that control differentiation/renewal using human Pluripotent Stem Cell (hPSC) differentiation into neural stem cells as a differentiation paradigm. Using multiplexed, genetically-encoded biosensors, we will quantitate hPSC single-cell dynamic signaling states by large-scale, multi-color, multi-day timelapse microscopy across millions of cells, to reveal with unparalleled precision how heterogeneous signaling states correlate with renewal/differentiation fates. Using computer vision approaches, we will automatically segment, track and lineage at scale each of the cells that were induced to self-renew or differentiate, and we will extract a panel of signaling, cell-cycle, pluripotency state, and cell morphodynamics features that quantify these dynamic processes. We will then mine these high-dimensional feature sets to build computational models that identify dynamic single-cell signaling patterns associated with robust fate transitions and predict actionable interventions that might cause those transitions. Lastly, using drug perturbations, and/or microfluidic/optogenetic actuators, we will quantitatively test those predictions by evoking synthetic dynamic signaling states that induce robust fate transitions. Our approach will help to significantly clarify the mechanistic basis of signaling-mediated human stem cell fate decisions, providing new avenues to robustly control stem cell fate. This might help establish a larger framework, broadly applicable to other hPSC lines and differentiation routes.

Embryos develop precisely at the multicellular level. Yet, stochasticity at the single cell level generates local variability in behaviors (e.g. in cell division, cell positioning, and gene expression). How is this apparent contradiction resolved? Do embryos compensate or possibly exploit local variability to adjust or correct patterns?
In mammalian embryos, the first developmental axis forms in the blastocyst when the outer trophoblasts (the future placenta) form a globe with an axis of proliferation/differentiation originating from the cluster of inner embryonic cells (the future embryo).
Here, we will investigate the principles underlying axis formation through a unique combination of stem cell-based embryology, quantitative imaging of the phenome of trophoblasts, and computational and statistical modeling. Using a novel blastocyst model formed solely with stem cells (Nicolas Rivron, The Netherlands), we will tune the embryonic signals and richly quantify the impact on trophoblast phenotypes, and their variability and precision in space (Shantanu Singh, USA), to model cells’ coordination during axis formation (Kyogo Kawaguchi, Japan).
This unique synergy will reveal how individual stem cells resolve the contrasting forces of single cell variability and multicellular guidance (e.g. embryonic inductions, neighbor coupling), to adjust and achieve a level of precision during the generation of an axis.

Osteoderms are hard calcified tissues that form within the skin of some animals. They resemble bone, hence the name, but are fundamentally different in several respects. Crocodile and armadillo skin plates, and turtle shells are among the most familiar examples, reportedly forming a protective armour against external predators and aiding locomotion. However, although less visible, osteoderms are also present in many lizards.
In terms of their shape, spatial distribution, and interaction, lizard osteoderms show the highest diversity in the animal kingdom, yet we know little about what drives this extraordinary diversity, how it is controlled, or how it originated. It could be a biproduct of other genetic differences or, more likely, a natural optimization to enhance osteoderm function, protective or otherwise, under conditions specific to each lizard type.
This project brings together a multidisciplinary team of expert engineers, developmental and evolutionary biologists from the UK, Canada and France to investigate the mechanisms underlying the development, patterning, and evolution of osteoderms in lizards. The team will use a range of advanced techniques (e.g. genetic analysis, material testing, imaging, and computer simulations) to investigate lizard osteoderms from the first molecular signalling events and cellular interactions, through to organismal level. Osteoderm mechanical properties will be characterised both as single units and as sheets so as to understand their function during feeding and locomotion.
This is a basic science project focused on a novel biological tissue and its evolutionary implications, but with a systems approach that may shed light on pathological calcifications, as well as aiding the development of biomimetic materials and structures. Most importantly it will train the next generation of scientists, in a multidisciplinary and international setting, providing them with a fundamental knowledge of biological tissues and a diverse skillset with which to address the global challenges of 21st century.

The gastrointestinal (GI) tract is efficiently organized to protect the host from potential dangerous stimuli and to tolerate commensal microbiota and food antigens. It hosts as many neurons as the spinal cord and more immune cells than all other compartments together. The innervation of the digestive tract is involved in determining the patterns of its movements, control of gastric acid secretion, release of gut hormones, modifying nutrient handling and interacting with the gut immune system. Infections of the GI tract can result in neuronal damage and dysregulation of these functions. The host laboratory has recently demonstrated that upon infection, in response to specific neurotransmitters, macrophages – a subset of innate immune cells – can acquire tissue-protective phenotype and minimize neuronal loss. Both immune and nervous systems are equipped with mechanisms allowing to store and recall information on previously encountered events. On this basis, I aim to examine whether GI infections trigger a neuro-immunological memory supporting tissue repair or response to subsequent infections. This is of fundamental and clinical interest, as interactions between immune and neuronal cells are proposed to be part of several disease processes, ranging from multiple sclerosis to irritable bowel syndrome (IBS).

The cell membrane is a double layer of lipid molecules. It plays a critical role in protecting the cell from its environment and in separating the different processes that take place within its interior. Membranes must change their shape in order for the cell to function, especially during cell division, and this depends on membrane curvature. At present, cells are only known to induce curvature by accumulating lipids in one of the layers or using specialised proteins. Our goal is to investigate a new mechanism of inducing membrane curvature by accumulation of hydrocarbons in the middle of the lipid layers that has not been observed before in nature.
These hydrocarbons are like the components of diesel fuel, and are found in photosynthetic cyanobacteria and algae – some of the most abundant and widespread organisms on Earth. Production of hydrocarbons in cyanobacteria or other microbes could substitute for liquid fuels derived from petroleum. As well, cyanobacteria and algae release hydrocarbons into the environment, where they are degraded by other bacteria that clean up oil spills. However despite their environmental and biotechnological importance, the exact cellular role of hydrocarbons has not been determined.
We recently discovered that hydrocarbons are essential for maintaining optimal cell size, growth and division, processes that require cell membranes to curve and bend, and found that cells lacking hydrocarbons have lipid membranes that are less curved or flexible. We showed that hydrocarbons integrate into the cell membranes, and used computer simulations to predict that this induces membrane curvature. To investigate this further, we have assembled a team of scientists from the UK, Sweden and New Zealand. By combining our different skills, we will analyse how hydrocarbons affect the physical properties of algal and cyanobacterial membranes by 1) running computer simulations; 2) studying membranes purified from algae and cyanobacteria; and 3) carrying out experiments on live cells. Together, these simulations and experiments will allow us to explore and quantify how hydrocarbons affect curvature and other membrane properties, and so conclusively establish the role of hydrocarbons in cells. As well as improving our understanding of biology, this information will assist the use of microbes for biofuel production and oil spill cleanup.

Hypothalamic tanycytes are sensory glia-like cells lining the walls of the 3rd ventricle (3V) that were proposed to respond to a variety of metabolic and environmental stimuli. The preoptic area (POA) is a hypothalamic region involved in thermoregulation whose nuclei are distributed around the 3V. The POA receives input from peripheral temperature receptors but also contains neurons that respond to deep-brain thermal changes, although the exact mechanism of this phenomenon is not clear. Due to the privileged position of tanycytes, with their somata directly contacting the cerebrospinal fluid and processes reaching portal blood vessels, we propose that tanycytes are part of the central temperature-sensing circuitry. This hypothesis is supported by the fact that they express two receptors, TRPM5 and TRPM3, which are known to be temperature-sensitive. In this project I will use transgenic mouse lines and employ a combination of electrophysiological, chemogenetic, optogenetic and imaging techniques to explore the sensory roles of tanycytes, mostly focusing on thermodetection. I will start with characterising sensory capabilities of tanycytes including their responsiveness to temperature changes and analysing their functional diversity. Then I will test whether tanycytes communicate with neurons in the POA and if so, I will attempt to identify the phenotype of these neurons. Lastly, I will perform in vivo experiments to test the effect of chemogenetic activation and inhibition of temperature-sensitive tanycytes on thermal effector responses as well as eating behaviour. Overall, I expect my study to shed light on the role tanycytes play in temperature detection and homeostasis.

Morphological plasticity is a key adaptive process allowing organisms to cope with changes in their environment. In animals, this process has been described in ephemeral organisms (e.g. flies, worms and mice) that typically experience a specific period in which development will respond to environmental signals producing long-lasting changes in animal body. In contrast, animals with extreme longevity are constantly patterning such that they must continuously adjust their developmental and physiological behaviours with the unpredictable fluctuations of food supply. To decipher the logic of such enhanced morphological plasticity, I am using the sea anemone Nematostella vectensis, a cnidarian laboratory model that exhibits a striking ability to adjust developmental patterns to the nutritional status of the environment while having a long lifespan. Based on preliminary data from the host lab, muscle is emerging as a central tissue that mediates the nutrient-dependent development of Nematostella tentacles. I will define this novel property of muscle cells in response to feeding using transgenic reporter lines. In parallel, I will also establish novel genetic tools to manipulate different muscle types and determine their specific contribution to post-embryonic development. I will also perform single-cell sequencing experiments to characterize the potential metabolic and developmental properties of muscles. Altogether, this proposed work will provide new insight into how morphological plasticity is encoded at the cellular and molecular levels in a long-lived animal.