TY - THES AB - Nonergodic systems, whose out-of-equilibrium dynamics fail to thermalize, provide a fascinating research direction both for fundamental reasons and for application in state of the art quantum devices. Going beyond the description of statistical mechanics, ergodicity breaking yields a new paradigm in quantum many-body physics, introducing novel phases of matter with no counterpart at equilibrium. In this Thesis, we address different open questions in the field, focusing on disorder-induced many-body localization (MBL) and on weak ergodicity breaking in kinetically constrained models. In particular, we contribute to the debate about transport in kinetically constrained models, studying the effect of $U(1)$ conservation and inversion-symmetry breaking in a family of quantum East models. Using tensor network techniques, we analyze the dynamics of large MBL systems beyond the limit of exact numerical methods. In this setting, we approach the debated topic of the coexistence of localized and thermal eigenstates separated by energy thresholds known as many-body mobility edges. Inspired by recent experiments, our work further investigates the localization of a small bath induced by the coupling to a large localized chain, the so-called MBL proximity effect. In the first Chapter, we introduce a family of particle-conserving kinetically constrained models, inspired by the quantum East model. The system we study features strong inversion-symmetry breaking, due to the nature of the correlated hopping. We show that these models host so-called quantum Hilbert space fragmentation, consisting of disconnected subsectors in an entangled basis, and further provide an analytical description of this phenomenon. We further probe its effect on dynamics of simple product states, showing revivals in fidelity and local observalbes. The study of dynamics within the largest subsector reveals an anomalous transient superdiffusive behavior crossing over to slow logarithmic dynamics at later times. This work suggests that particle conserving constrained models with inversion-symmetry breaking realize new universality classes of dynamics and invite their further theoretical and experimental studies. Next, we use kinetic constraints and disorder to design a model with many-body mobility edges in particle density. This feature allows to study the dynamics of localized and thermal states in large systems beyond the limitations of previous studies. The time-evolution shows typical signatures of localization at small densities, replaced by thermal behavior at larger densities. Our results provide evidence in favor of the stability of many-body mobility edges, which was recently challenged by a theoretical argument. To support our findings, we probe the mechanism proposed as a cause of delocalization in many-body localized systems with mobility edges suggesting its ineffectiveness in the model studied. In the last Chapter of this Thesis, we address the topic of many-body localization proximity effect. We study a model inspired by recent experiments, featuring Anderson localized coupled to a small bath of free hard-core bosons. The interaction among the two particle species results in non-trivial dynamics, which we probe using tensor network techniques. Our simulations show convincing evidence of many-body localization proximity effect when the bath is composed by a single free particle and interactions are strong. We furthter observe an anomalous entanglement dynamics, which we explain through a phenomenological theory. Finally, we extract highly excited eigenstates of large systems, providing supplementary evidence in favor of our findings. AU - Brighi, Pietro ID - 12732 SN - 2663-337X TI - Ergodicity breaking in disordered and kinetically constrained quantum many-body systems ER - TY - THES AB - During development, tissues undergo changes in size and shape to form functional organs. Distinct cellular processes such as cell division and cell rearrangements underlie tissue morphogenesis. Yet how the distinct processes are controlled and coordinated, and how they contribute to morphogenesis is poorly understood. In our study, we addressed these questions using the developing mouse neural tube. This epithelial organ transforms from a flat epithelial sheet to an epithelial tube while increasing in size and undergoing morpho-gen-mediated patterning. The extent and mechanism of neural progenitor rearrangement within the developing mouse neuroepithelium is unknown. To investigate this, we per-formed high resolution lineage tracing analysis to quantify the extent of epithelial rear-rangement at different stages of neural tube development. We quantitatively described the relationship between apical cell size with cell cycle dependent interkinetic nuclear migra-tions (IKNM) and performed high cellular resolution live imaging of the neuroepithelium to study the dynamics of junctional remodeling. Furthermore, developed a vertex model of the neuroepithelium to investigate the quantitative contribution of cell proliferation, cell differentiation and mechanical properties to the epithelial rearrangement dynamics and validated the model predictions through functional experiments. Our analysis revealed that at early developmental stages, the apical cell area kinetics driven by IKNM induce high lev-els of cell rearrangements in a regime of high junctional tension and contractility. After E9.5, there is a sharp decline in the extent of cell rearrangements, suggesting that the epi-thelium transitions from a fluid-like to a solid-like state. We found that this transition is regulated by the growth rate of the tissue, rather than by changes in cell-cell adhesion and contractile forces. Overall, our study provides a quantitative description of the relationship between tissue growth, cell cycle dynamics, epithelia rearrangements and the emergent tissue material properties, and novel insights on how epithelial cell dynamics influences tissue morphogenesis. AU - Bocanegra, Laura ID - 13081 SN - 2663 - 337X TI - Epithelial dynamics during mouse neural tube development ER - TY - THES AB - The extension of extremal combinatorics to the setting of exterior algebra is a work in progress that gained attention recently. In this thesis, we study the combinatorial structure of exterior algebra by introducing a dictionary that translates the notions from the set systems into the framework of exterior algebra. We show both generalizations of celebrated Erdös--Ko--Rado theorem and Hilton--Milner theorem to the setting of exterior algebra in the simplest non-trivial case of two-forms. AU - Köse, Seyda ID - 13331 SN - 2791-4585 TI - Exterior algebra and combinatorics ER - TY - THES AB - Animals exhibit a remarkable ability to learn and remember new behaviors, skills, and associations throughout their lifetime. These capabilities are made possible thanks to a variety of changes in the brain throughout adulthood, regrouped under the term "plasticity". Some cells in the brain —neurons— and specifically changes in the connections between neurons, the synapses, were shown to be crucial for the formation, selection, and consolidation of memories from past experiences. These ongoing changes of synapses across time are called synaptic plasticity. Understanding how a myriad of biochemical processes operating at individual synapses can somehow work in concert to give rise to meaningful changes in behavior is a fascinating problem and an active area of research. However, the experimental search for the precise plasticity mechanisms at play in the brain is daunting, as it is difficult to control and observe synapses during learning. Theoretical approaches have thus been the default method to probe the plasticity-behavior connection. Such studies attempt to extract unifying principles across synapses and model all observed synaptic changes using plasticity rules: equations that govern the evolution of synaptic strengths across time in neuronal network models. These rules can use many relevant quantities to determine the magnitude of synaptic changes, such as the precise timings of pre- and postsynaptic action potentials, the recent neuronal activity levels, the state of neighboring synapses, etc. However, analytical studies rely heavily on human intuition and are forced to make simplifying assumptions about plasticity rules. In this thesis, we aim to assist and augment human intuition in this search for plasticity rules. We explore whether a numerical approach could automatically discover the plasticity rules that elicit desired behaviors in large networks of interconnected neurons. This approach is dubbed meta-learning synaptic plasticity: learning plasticity rules which themselves will make neuronal networks learn how to solve a desired task. We first write all the potential plasticity mechanisms to consider using a single expression with adjustable parameters. We then optimize these plasticity parameters using evolutionary strategies or Bayesian inference on tasks known to involve synaptic plasticity, such as familiarity detection and network stabilization. We show that these automated approaches are powerful tools, able to complement established analytical methods. By comprehensively screening plasticity rules at all synapse types in realistic, spiking neuronal network models, we discover entire sets of degenerate plausible plasticity rules that reliably elicit memory-related behaviors. Our approaches allow for more robust experimental predictions, by abstracting out the idiosyncrasies of individual plasticity rules, and provide fresh insights on synaptic plasticity in spiking network models. AU - Confavreux, Basile J ID - 14422 SN - 2663 - 337X TI - Synapseek: Meta-learning synaptic plasticity rules ER - TY - THES AB - Superconductivity has many important applications ranging from levitating trains over qubits to MRI scanners. The phenomenon is successfully modeled by Bardeen-Cooper-Schrieffer (BCS) theory. From a mathematical perspective, BCS theory has been studied extensively for systems without boundary. However, little is known in the presence of boundaries. With the help of numerical methods physicists observed that the critical temperature may increase in the presence of a boundary. The goal of this thesis is to understand the influence of boundaries on the critical temperature in BCS theory and to give a first rigorous justification of these observations. On the way, we also study two-body Schrödinger operators on domains with boundaries and prove additional results for superconductors without boundary. BCS theory is based on a non-linear functional, where the minimizer indicates whether the system is superconducting or in the normal, non-superconducting state. By considering the Hessian of the BCS functional at the normal state, one can analyze whether the normal state is possibly a minimum of the BCS functional and estimate the critical temperature. The Hessian turns out to be a linear operator resembling a Schrödinger operator for two interacting particles, but with more complicated kinetic energy. As a first step, we study the two-body Schrödinger operator in the presence of boundaries. For Neumann boundary conditions, we prove that the addition of a boundary can create new eigenvalues, which correspond to the two particles forming a bound state close to the boundary. Second, we need to understand superconductivity in the translation invariant setting. While in three dimensions this has been extensively studied, there is no mathematical literature for the one and two dimensional cases. In dimensions one and two, we compute the weak coupling asymptotics of the critical temperature and the energy gap in the translation invariant setting. We also prove that their ratio is independent of the microscopic details of the model in the weak coupling limit; this property is referred to as universality. In the third part, we study the critical temperature of superconductors in the presence of boundaries. We start by considering the one-dimensional case of a half-line with contact interaction. Then, we generalize the results to generic interactions and half-spaces in one, two and three dimensions. Finally, we compare the critical temperature of a quarter space in two dimensions to the critical temperatures of a half-space and of the full space. AU - Roos, Barbara ID - 14374 SN - 2663 - 337X TI - Boundary superconductivity in BCS theory ER - TY - THES AB - Payment channel networks are a promising approach to improve the scalability bottleneck of cryptocurrencies. Two design principles behind payment channel networks are efficiency and privacy. Payment channel networks improve efficiency by allowing users to transact in a peer-to-peer fashion along multi-hop routes in the network, avoiding the lengthy process of consensus on the blockchain. Transacting over payment channel networks also improves privacy as these transactions are not broadcast to the blockchain. Despite the influx of recent protocols built on top of payment channel networks and their analysis, a common shortcoming of many of these protocols is that they typically focus only on either improving efficiency or privacy, but not both. Another limitation on the efficiency front is that the models used to model actions, costs and utilities of users are limited or come with unrealistic assumptions. This thesis aims to address some of the shortcomings of recent protocols and algorithms on payment channel networks, particularly in their privacy and efficiency aspects. We first present a payment route discovery protocol based on hub labelling and private information retrieval that hides the route query and is also efficient. We then present a rebalancing protocol that formulates the rebalancing problem as a linear program and solves the linear program using multiparty computation so as to hide the channel balances. The rebalancing solution as output by our protocol is also globally optimal. We go on to develop more realistic models of the action space, costs, and utilities of both existing and new users that want to join the network. In each of these settings, we also develop algorithms to optimise the utility of these users with good guarantees on the approximation and competitive ratios. AU - Yeo, Michelle X ID - 14506 SN - 2663 - 337X TI - Advances in efficiency and privacy in payment channel network analysis ER - TY - THES AB - Most motions of many-body systems at any scale in nature with sufficient degrees of freedom tend to be chaotic; reaching from the orbital motion of planets, the air currents in our atmosphere, down to the water flowing through our pipelines or the movement of a population of bacteria. To the observer it is therefore intriguing when a moving collective exhibits order. Collective motion of flocks of birds, schools of fish or swarms of self-propelled particles or robots have been studied extensively over the past decades but the mechanisms involved in the transition from chaos to order remain unclear. Here, the interactions, that in most systems give rise to chaos, sustain order. In this thesis we investigate mechanisms that preserve, destabilize or lead to the ordered state. We show that endothelial cells migrating in circular confinements transition to a collective rotating state and concomitantly synchronize the frequencies of nucleating actin waves within individual cells. Consequently, the frequency dependent cell migration speed uniformizes across the population. Complementary to the WAVE dependent nucleation of traveling actin waves, we show that in leukocytes the actin polymerization depending on WASp generates pushing forces locally at stationary patches. Next, in pipe flows, we study methods to disrupt the self–sustaining cycle of turbulence and therefore relaminarize the flow. While we find in pulsating flow conditions that turbulence emerges through a helical instability during the decelerating phase. Finally, we show quantitatively in brain slices of mice that wild-type control neurons can compensate the migratory deficits of a genetically modified neuronal sub–population in the developing cortex. AU - Riedl, Michael ID - 12726 SN - 2663-337X TI - Synchronization in collectively moving active matter ER - TY - THES AB - Most motions of many-body systems at any scale in nature with sufficient degrees of freedom tend to be chaotic; reaching from the orbital motion of planets, the air currents in our atmosphere, down to the water flowing through our pipelines or the movement of a population of bacteria. To the observer it is therefore intriguing when a moving collective exhibits order. Collective motion of flocks of birds, schools of fish or swarms of self-propelled particles or robots have been studied extensively over the past decades but the mechanisms involved in the transition from chaos to order remain unclear. Here, the interactions, that in most systems give rise to chaos, sustain order. In this thesis we investigate mechanisms that preserve, destabilize or lead to the ordered state. We show that endothelial cells migrating in circular confinements transition to a collective rotating state and concomitantly synchronize the frequencies of nucleating actin waves within individual cells. Consequently, the frequency dependent cell migration speed uniformizes across the population. Complementary to the WAVE dependent nucleation of traveling actin waves, we show that in leukocytes the actin polymerization depending on WASp generates pushing forces locally at stationary patches. Next, in pipe flows, we study methods to disrupt the self--sustaining cycle of turbulence and therefore relaminarize the flow. While we find in pulsating flow conditions that turbulence emerges through a helical instability during the decelerating phase. Finally, we show quantitatively in brain slices of mice that wild-type control neurons can compensate the migratory deficits of a genetically modified neuronal sub--population in the developing cortex. AU - Riedl, Michael ID - 14530 KW - Synchronization KW - Collective Movement KW - Active Matter KW - Cell Migration KW - Active Colloids SN - 2663 - 337X TI - Synchronization in collectively moving active matter ER - TY - THES AB - Superconductor-semiconductor heterostructures currently capture a significant amount of research interest and they serve as the physical platform in many proposals towards topological quantum computation. Despite being under extensive investigations, historically using transport techniques, the basic properties of the interface between the superconductor and the semiconductor remain to be understood. In this thesis, two separate studies on the Al-InAs heterostructures are reported with the first focusing on the physics of the material motivated by the emergence of a new phase, the Bogoliubov-Fermi surface. The second focuses on a technological application, a gate-tunable Josephson parametric amplifier. In the first study, we investigate the hypothesized unconventional nature of the induced superconductivity at the interface between the Al thin film and the InAs quantum well. We embed a two-dimensional Al-InAs hybrid system in a resonant microwave circuit allowing measurements of change in inductance. The behaviour of the resonance in a range of temperature and in-plane magnetic field has been studied and compared with the theory of conventional s-wave superconductor and a two-component theory that includes both contribution of the $s$-wave pairing in Al and the intraband $p \pm ip$ pairing in InAs. Measuring the temperature dependence of resonant frequency, no discrepancy is found between data and the conventional theory. We observe the breakdown of superconductivity due to an applied magnetic field which contradicts the conventional theory. In contrast, the data can be captured quantitatively by fitting to a two-component model. We find the evidence of the intraband $p \pm ip$ pairing in the InAs and the emergence of the Bogoliubov-Fermi surfaces due to magnetic field with the characteristic value $B^* = 0.33~\mathrm{T}$. From the fits, the sheet resistance of Al, the carrier density and mobility in InAs are determined. By systematically studying the anisotropy of the circuit response, we find weak anisotropy for $B < B^*$ and increasingly strong anisotropy for $B > B^*$ resulting in a pronounced two-lobe structure in polar plot of frequency versus field angle. Strong resemblance between the field dependence of dissipation and superfluid density hints at a hidden signature of the Bogoliubov-Fermi surface that is burried in the dissipation data. In the second study, we realize a parametric amplifier with a Josephson field effect transistor as the active element. The device's modest construction consists of a gated SNS weak link embedded at the center of a coplanar waveguide resonator. By applying a gate voltage, the resonant frequency is field-effect tunable over a range of 2 GHz. Modelling the JoFET minimally as a parallel RL circuit, the dissipation introduced by the JoFET can be quantitatively related to the gate voltage. We observed gate-tunable Kerr nonlinearity qualitatively in line with expectation. The JoFET amplifier has 20 dB of gain, 4 MHz of instantaneous bandwidth, and a 1dB compression point of -125.5 dBm when operated at a fixed resonant frequency. In general, the signal-to-noise ratio is improved by 5-7 dB when the JoFET amplifier is activated compared. The noise of the measurement chain and insertion loss of relevant circuit elements are calibrated to determine the expected and the real noise performance of the JoFET amplifier. As a quantification of the noise performance, the measured total input-referred noise of the JoFET amplifier is in good agreement with the estimated expectation which takes device loss into account. We found that the noise performance of the device reported in this document approaches one photon of total input-referred added noise which is the quantum limit imposed in nondegenerate parametric amplifier. AU - Phan, Duc T ID - 14547 KW - superconductor-semiconductor KW - superconductivity KW - Al KW - InAs KW - p-wave KW - superconductivity KW - JPA KW - microwave SN - 2663 - 337X TI - Resonant microwave spectroscopy of Al-InAs ER - TY - THES AB - Females and males across species are subject to divergent selective pressures arising from di↵erent reproductive interests and ecological niches. This often translates into a intricate array of sex-specific natural and sexual selection on traits that have a shared genetic basis between both sexes, causing a genetic sexual conflict. The resolution of this conflict mostly relies on the evolution of sex-specific expression of the shared genes, leading to phenotypic sexual dimorphism. Such sex-specific gene expression is thought to evolve via modifications of the genetic networks ultimately linked to sex-determining transcription factors. Although much empirical and theoretical evidence supports this standard picture of the molecular basis of sexual conflict resolution, there still are a few open questions regarding the complex array of selective forces driving phenotypic di↵erentiation between the sexes, as well as the molecular mechanisms underlying sexspecific adaptation. I address some of these open questions in my PhD thesis. First, how do patterns of phenotypic sexual dimorphism vary within populations, as a response to the temporal and spatial changes in sex-specific selective forces? To tackle this question, I analyze the patterns of sex-specific phenotypic variation along three life stages and across populations spanning the whole geographical range of Rumex hastatulus, a wind-pollinated angiosperm, in the first Chapter of the thesis. Second, how do gene expression patterns lead to phenotypic dimorphism, and what are the molecular mechanisms underlying the observed transcriptomic variation? I address this question by examining the sex- and tissue-specific expression variation in newly-generated datasets of sex-specific expression in heads and gonads of Drosophila melanogaster. I additionally used two complementary approaches for the study of the genetic basis of sex di↵erences in gene expression in the second and third Chapters of the thesis. Third, how does intersex correlation, thought to be one of the main aspects constraining the ability for the two sexes to decouple, interact with the evolution of sexual dimorphism? I develop models of sex-specific stabilizing selection, mutation and drift to formalize common intuition regarding the patterns of covariation between intersex correlation and sexual dimorphism in the fourth Chapter of the thesis. Alltogether, the work described in this PhD thesis provides useful insights into the links between genetic, transcriptomic and phenotypic layers of sex-specific variation, and contributes to our general understanding of the dynamics of sexual dimorphism evolution. AU - Puixeu Sala, Gemma ID - 14058 SN - 2663-337X TI - The molecular basis of sexual dimorphism: Experimental and theoretical characterization of phenotypic, transcriptomic and genetic patterns of sex-specific adaptation ER - TY - THES AU - Sack, Stefan ID - 14622 SN - 2663 - 337X TI - Improving variational quantum algorithms: Innovative initialization techniques and extensions to qudit systems ER - TY - THES AU - Stopp, Julian A ID - 14697 SN - 2663 - 337X TI - Neutrophils on the hunt: Migratory strategies employed by neutrophils to fulfill their effector function ER - TY - THES AB - For self-incompatibility (SI) to be stable in a population, theory predicts that sufficient inbreeding depression (ID) is required: the fitness of offspring from self-mated individuals must be low enough to prevent the spread of self-compatibility (SC). Reviews of natural plant populations have supported this theory, with SI species generally showing high levels of ID. However, there is thought to be an under-sampling of self-incompatible taxa in the current literature. In this thesis, I study inbreeding depression in the SI plant species Antirrhinum majus using both greenhouse crosses and a large collected field dataset. Additionally, the gametophytic S-locus of A. majus is highly heterozygous and polymorphic, thus making assembly and discovery of S-alleles very difficult. Here, 206 new alleles of the male component SLFs are presented, along with a phylogeny showing the high conservation with alleles from another Antirrhinum species. Lastly, selected sites within the protein structure of SLFs are investigated, with one site in particular highlighted as potentially being involved in the SI recognition mechanism. AU - Arathoon, Louise S ID - 14651 SN - 2663 - 337X TI - Investigating inbreeding depression and the self-incompatibility locus of Antirrhinum majus ER - TY - THES AB - Stochastic systems provide a formal framework for modelling and quantifying uncertainty in systems and have been widely adopted in many application domains. Formal verification and control of finite state stochastic systems, a subfield of formal methods also known as probabilistic model checking, is well studied. In contrast, formal verification and control of infinite state stochastic systems have received comparatively less attention. However, infinite state stochastic systems commonly arise in practice. For instance, probabilistic models that contain continuous probability distributions such as normal or uniform, or stochastic dynamical systems which are a classical model for control under uncertainty, both give rise to infinite state systems. The goal of this thesis is to contribute to laying theoretical and algorithmic foundations of fully automated formal verification and control of infinite state stochastic systems, with a particular focus on systems that may be executed over a long or infinite time. We consider formal verification of infinite state stochastic systems in the setting of static analysis of probabilistic programs and formal control in the setting of controller synthesis in stochastic dynamical systems. For both problems, we present some of the first fully automated methods for probabilistic (a.k.a. quantitative) reachability and safety analysis applicable to infinite time horizon systems. We also advance the state of the art of probability 1 (a.k.a. qualitative) reachability analysis for both problems. Finally, for formal controller synthesis in stochastic dynamical systems, we present a novel framework for learning neural network control policies in stochastic dynamical systems with formal guarantees on correctness with respect to quantitative reachability, safety or reach-avoid specifications. AU - Zikelic, Dorde ID - 14539 SN - 2663 - 337X TI - Automated verification and control of infinite state stochastic systems ER - TY - THES AB - Within the human body, the brain exhibits the highest rate of energy consumption amongst all organs, with the majority of generated ATP being utilized to sustain neuronal activity. Therefore, the metabolism of the mature cerebral cortex is geared towards preserving metabolic homeostasis whilst generating significant amounts of energy. This requires a precise interplay between diverse metabolic pathways, spanning from a tissue-wide scale to the level of individual neurons. Disturbances to this delicate metabolic equilibrium, such as those resulting from maternal malnutrition or mutations affecting metabolic enzymes, often result in neuropathological variants of neurodevelopment. For instance, mutations in SLC7A5, a transporter of metabolically essential large neutral amino acids (LNAAs), have been associated with autism and microcephaly. However, despite recent progress in the field, the extent of metabolic restructuring that occurs within the developing brain and the corresponding alterations in nutrient demands during various critical periods remain largely unknown. To investigate this, we performed metabolomic profiling of the murine cerebral cortex to characterize the metabolic state of the forebrain at different developmental stages. We found that the developing cortex undergoes substantial metabolic reprogramming, with specific sets of metabolites displaying stage-specific changes. According to our observations, we determined a distinct temporal period in postnatal development during which the cortex displays heightened reliance on LNAAs. Hence, using a conditional knock-out mouse model, we deleted Slc7a5 in neural cells, allowing us to monitor the impact of a perturbed neuronal metabolic state across multiple developmental stages of corticogenesis. We found that manipulating the levels of essential LNAAs in cortical neurons in vivo affects one particular perinatal developmental period critical for cortical network refinement. Abnormally low intracellular LNAA levels result in cell-autonomous alterations in neuronal lipid metabolism, excitability, and survival during this particular time window. Although most of the effects of Slc7a5 deletion on neuronal physiology are transient, derailment of these processes during this brief but crucial window leads to long-term circuit dysfunction in mice. In conclusion, out data indicate that the cerebral cortex undergoes significant metabolic reorganization during development. This process involves the intricate integration of multiple metabolic pathways to ensure optimal neuronal function throughout different developmental stages. Our findings offer a paradigm for understanding how neurons synchronize the expression of nutrient-related genes with their activity to allow proper brain maturation. Further, our results demonstrate that disruptions in these precisely calibrated metabolic processes during critical periods of brain development may result in neuropathological outcomes in mice and in humans. AU - Knaus, Lisa ID - 13107 SN - 2663 - 337X TI - The metabolism of the developing brain : How large neutral amino acids modulate perinatal neuronal excitability and survival ER - TY - THES AB - Cell division in Escherichia coli is performed by the divisome, a multi-protein complex composed of more than 30 proteins. The divisome spans from the cytoplasm through the inner membrane to the cell wall and the outer membrane. Divisome assembly is initiated by a cytoskeletal structure, the so-called Z-ring, which localizes at the center of the E. coli cell and determines the position of the future cell septum. The Z-ring is composed of the highly conserved bacterial tubulin homologue FtsZ, which forms treadmilling filaments. These filaments are recruited to the inner membrane by FtsA, a highly conserved bacterial actin homologue. FtsA interacts with other proteins in the periplasm and thus connects the cytoplasmic and periplasmic components of the divisome. A previous model postulated that FtsA regulates maturation of the divisome by switching from an oligomeric, inactive state to a monomeric and active state. This model was based mostly on in vivo studies, as a biochemical characterization of FtsA has been hampered by difficulties in purifying the protein. Here, we studied FtsA using an in vitro reconstitution approach and aimed to answer two questions: (i) How are dynamics from cytoplasmic, treadmilling FtsZ filaments coupled to proteins acting in the periplasmic space and (ii) How does FtsA regulate the maturation of the divisome? We found that the cytoplasmic peptides of the transmembrane proteins FtsN and FtsQ interact directly with FtsA and can follow the spatiotemporal signal of FtsA/Z filaments. When we investigated the underlying mechanism by imaging single molecules of FtsNcyto, we found the peptide to interact transiently with FtsA. An in depth analysis of the single molecule trajectories helped to postulate a model where PG synthases follow the dynamics of FtsZ by a diffusion and capture mechanism. Following up on these findings we were interested in how the self-interaction of FtsA changes when it encounters FtsNcyto and if we can confirm the proposed oligomer-monomer switch. For this, we compared the behavior of the previously identified, hyperactive mutant FtsA R286W with wildtype FtsA. The mutant outperforms WT in mirroring and transmitting the spatiotemporal signal of treadmilling FtsZ filaments. Surprisingly however, we found that this was not due to a difference in the self-interaction strength of the two variants, but a difference in their membrane residence time. Furthermore, in contrast to our expectations, upon binding of FtsNcyto the measured self-interaction of FtsA actually increased. We propose that FtsNcyto induces a rearrangement of the oligomeric architecture of FtsA. In further consequence this change leads to more persistent FtsZ filaments which results in a defined signalling zone, allowing formation of the mature divisome. The observed difference between FtsA WT and R286W is due to the vastly different membrane turnover of the proteins. R286W cycles 5-10x faster compared to WT which allows to sample FtsZ filaments at faster frequencies. These findings can explain the observed differences in toxicity for overexpression of FtsA WT and R286W and help to understand how FtsA regulates divisome maturation. AU - Radler, Philipp ID - 14280 KW - Cell Division KW - Reconstitution KW - FtsZ KW - FtsA KW - Divisome KW - E.coli SN - 2663-337X TI - Spatiotemporal signaling during assembly of the bacterial divisome ER - TY - THES AB - Semiconductor-superconductor hybrid systems are the harbour of many intriguing mesoscopic phenomena. This material combination leads to spatial variations of the superconducting properties, which gives rise to Andreev bound states (ABSs). Some of these states might exhibit remarkable properties that render them highly desirable for topological quantum computing. The most prominent and hunted of such states are Majorana zero modes (MZMs), quasiparticles equals to their own quasiparticles that they follow non-abelian statistics. In this thesis, we first introduce the general framework of such hybrid systems and, then, we unveil a series of mesoscopic phenomena that we discovered. Firstly, we show tunneling spectroscopy experiments on full-shell nanowires (NWs) showing that unwanted quantum-dot states coupled to superconductors (Yu-Shiba-Rusinov states) can mimic MZMs signatures. Then, we introduce a novel protocol which allowed the integration of tunneling spectroscopy with Coulomb spectroscopy within the same device. Employing this approach on both full-shell NWs and partial-shell NWs, we demonstrated that longitudinally confined states reveal charge transport phenomenology similar to the one expected for MZMs. These findings shed light on the intricate interplay between superconductivity and quantum confinement, which brought us to explore another material platform, i.e. a two-dimensional Germanium hole gas. After developing a robust way to induce superconductivity in such system, we showed how to engineer the proximity effect and we revealed a superconducting hard gap. Finally, we created a superconducting radio frequency driven ideal diode and a generator of non-sinusoidal current-phase relations. Our results open the path for the exploration of protected superconducting qubits and more complex hybrid devices in planar Germanium, like Kitaev chains and hybrid qubit devices. AU - Valentini, Marco ID - 13286 SN - 2663 - 337X TI - Mesoscopic phenomena in hybrid semiconductor-superconductor nanodevices : From full-shell nanowires to two-dimensional hole gas in germanium ER - TY - THES AB - Social insects fight disease using their individual immune systems and the cooperative sanitary behaviors of colony members. These social defenses are well explored against externally-infecting pathogens, but little is known about defense strategies against internally-infecting pathogens, such as viruses. Viruses are ubiquitous and in the last decades it has become evident that also many ant species harbor viruses. We present one of the first studies addressing transmission dynamics and collective disease defenses against viruses in ants on a mechanistic level. I successfully established an experimental ant host – viral pathogen system as a model for the defense strategies used by social insects against internal pathogen infections, as outlined in the third chapter. In particular, we studied how garden ants (Lasius neglectus) defend themselves and their colonies against the generalist insect virus CrPV (cricket paralysis virus). We chose microinjections of virus directly into the ants’ hemolymph because it allowed us to use a defined exposure dose. Here we show that this is a good model system, as the virus is replicating and thus infecting the host. The ants mount a clear individual immune response against the viral infection, which is characterized by a specific siRNA pattern, namely siRNAs mapping against the viral genome with a peak of 21 and 22 bp long fragments. The onset of this immune response is consistent with the timeline of viral replication that starts already within two days post injection. The disease manifests in decreased survival over a course of two to three weeks. Regarding group living, we find that infected ants show a strong individual immune response, but that their course of disease is little affected by nestmate presence, as described in chapter four. Hence, we do not find social immunity in the context of viral infections in ants. Nestmates, however, can contract the virus. Using Drosophila S2R+ cells in culture, we showed that 94 % of the nestmates contract active virus within four days of social contact to an infected individual. Virus is transmitted in low doses, thus not causing disease transmission within the colony. While virus can be transmitted during short direct contacts, we also assume transmission from deceased ants and show that the nestmates’ immune system gets activated after contracting a low viral dose. We find considerable potential for indirect transmission via the nest space. Virus is shed to the nest, where it stays viable for one week and is also picked up by other ants. Apart from that, we want to underline the potential of ant poison as antiviral agent. We determined that ant poison successfully inactivates CrPV in vitro. However, we found no evidence for effective poison use to sanitize the nest space. On the other hand, local application of ant poison by oral poison uptake, which is part of the ants prophylactic behavioral repertoire, probably contributes to keeping the gut of each individual sanitized. We hypothesize that oral poison uptake might be the reason why we did not find viable virus in the trophallactic fluid. The fifth chapter encompasses preliminary data on potential social immunization. However, our experiments do not confirm an actual survival benefit for the nestmates upon pathogen challenge under the given experimental settings. Nevertheless, we do not want to rule out the possibility for nestmate immunization, but rather emphasize that considering different experimental timelines and viral doses would provide a multitude of options for follow-up experiments. In conclusion, we find that prophylactic individual behaviors, such as oral poison uptake, might play a role in preventing viral disease transmission. Compared to colony defense against external pathogens, internal pathogen infections require a stronger component of individual physiological immunity than behavioral social immunity, yet could still lead to collective protection. AU - Franschitz, Anna ID - 13984 SN - 2663 - 337X TI - Individual and social immunity against viral infections in ants ER - TY - THES AB - Morphogens are signaling molecules that are known for their prominent role in pattern formation within developing tissues. In addition to patterning, morphogens also control tissue growth. However, the underlying mechanisms are poorly understood. We studied the role of morphogens in regulating tissue growth in the developing vertebrate neural tube. In this system, opposing morphogen gradients of Shh and BMP establish the dorsoventral pattern of neural progenitor domains. Perturbations in these morphogen pathways result in alterations in tissue growth and cell cycle progression, however, it has been unclear what cellular process is affected. To address this, we analysed the rates of cell proliferation and cell death in mouse mutants in which signaling is perturbed, as well as in chick neural plate explants exposed to defined concentrations of signaling activators or inhibitors. Our results indicated that the rate of cell proliferation was not altered in these assays. By contrast, both the Shh and BMP signaling pathways had profound effects on neural progenitor survival. Our results indicate that these pathways synergise to promote cell survival within neural progenitors. Consistent with this, we found that progenitors within the intermediate region of the neural tube, where the combined levels of Shh and BMP are the lowest, are most prone to cell death when signaling activity is inhibited. In addition, we found that downregulation of Shh results in increased apoptosis within the roof plate, which is the dorsal source of BMP ligand production. This revealed a cross-interaction between the Shh and BMP morphogen signaling pathways that may be relevant for understanding how gradients scale in neural tubes with different overall sizes. We further studied the mechanism acting downstream of Shh in cell survival regulation using genetic and genomic approaches. We propose that Shh transcriptionally regulates a non-canonical apoptotic pathway. Altogether, our study points to a novel role of opposing morphogen gradients in tissue size regulation and provides new insights into complex interactions between Shh and BMP signaling gradients in the neural tube. AU - Kuzmicz-Kowalska, Katarzyna ID - 14323 SN - 2663 - 337X TI - Regulation of neural progenitor survival by Shh and BMP in the developing spinal cord ER - TY - THES AU - Hennessey-Wesen, Mike ID - 14641 KW - microfluidics KW - miceobiology KW - mutations KW - quorum sensing SN - 2663 - 337X TI - Adaptive mutation in E. coli modulated by luxS ER -