@article{21253, abstract = {We solve a problem of Dujmović and Wood (2007) by showing that a complete convex geometric graph on n vertices cannot be decomposed into fewer than n - 1 star-forests, each consisting of noncrossing edges. This bound is clearly tight. We also discuss similar questions for abstract graphs.}, author = {Pach, János and Saghafian, Morteza and Schnider, Patrick}, issn = {0925-7721}, journal = {Computational Geometry}, publisher = {Elsevier}, title = {{Decomposition of geometric graphs into star-forests}}, doi = {10.1016/j.comgeo.2025.102186}, volume = {129}, year = {2025}, } @phdthesis{18979, abstract = {Topological Data Analysis (TDA) is a discipline utilizing the mathematical field of topology to study data, most prominently collections of point sets. This thesis summarizes three projects related to computations in TDA. The first one establishes a variant of TDA for chromatic point sets, where each point is given a color. For example, we are given positions of cells within a tumor microenvironment, and color the cancerous cells red, and the immune cells blue. The aim is then to give a quantitative description of how the two or more sets of points spatially interact. Building on image, kernel and cokernel variants of persistent homology, we suggest six-packs of persistent diagrams as such a descriptor. We describe a construction of a chromatic alpha complex, which enables efficient computation of several variants of the six-packs. We give topological descriptions of natural subcomplexes of the chromatic alpha complex, and show that the radii of the simplices form a discrete Morse function. Finally, we provide an implementation of the presented chromatic TDA pipeline. The second part aims to translate a powerful tool of sheaf theory to elementary terms using labeled matrices. The goal is to enable their use in computational settings. We show that derived categories of sheaves over finite posets have, up to isomorphism, unique objects---minimal injective resolutions---and give a concrete algorithm to compute them. We further describe simple algorithms to compute derived pushforwards and pullbacks for monotonic maps, and their proper variants for inclusions, and demonstrate their tractability by providing an implementation. Finally, we suggest a discrete definition of microsupport and show desirable properties inspired by discrete Morse theory. In the last part, we present a collection of observations about collapses. We give a characterization of collapsibility in terms of unitriangular submatrices of the boundary matrix, a cotree-tree decomposition, and the optimal solution to a variant of the Procrustes problem. We establish relation between dual collapses and relative Morse theory and pose several open questions. Finally, focusing on complexes embedded in the three-dimensional Euclidean space, we describe a relation between the collapsibility and the triviality of a polygonal knot.}, author = {Draganov, Ondrej}, issn = {2663-337X}, keywords = {topological data analysis, chromatic point set, alpha complex, persistent homology, six pack, sheaf, microlocal discrete Morse, injective resolution, collapse, knot, discrete Morse theory}, pages = {140}, publisher = {Institute of Science and Technology Austria}, title = {{Structures and computations in topological data analysis}}, doi = {10.15479/at:ista:18979}, year = {2025}, } @article{20323, abstract = {We establish several results combining discrete Morse theory and microlocal sheaf theory in the setting of finite posets and simplicial complexes. Our primary tool is a computationally tractable description of the bounded derived category of sheaves on a poset with the Alexandrov topology. We prove that each bounded complex of sheaves on a finite poset admits a unique (up to isomorphism of complexes) minimal injective resolution, and we provide algorithms for computing minimal injective resolution of an injective complex, as well as several useful functors between derived categories of sheaves. For the constant sheaf on a simplicial complex, we give asymptotically tight bounds on the complexity of computing the minimal injective resolution using those algorithms. Our main result is a novel definition of the discrete microsupport of a bounded complex of sheaves on a finite poset. We detail several foundational properties of the discrete microsupport, as well as a microlocal generalization of the discrete homological Morse theorem and Morse inequalities.}, author = {Brown, Adam and Draganov, Ondrej}, issn = {0022-4049}, journal = {Journal of Pure and Applied Algebra}, number = {10}, publisher = {Elsevier}, title = {{Discrete microlocal Morse theory}}, doi = {10.1016/j.jpaa.2025.108068}, volume = {229}, year = {2025}, } @article{20591, abstract = {In this paper we derive estimates for the Hessian of the logarithm (log-Hessian) for solutions to the heat equation. For initial data in the form of log-Lipschitz perturbation of strongly log-concave measures, the log-Hessian admits an explicit, uniform (in space) lower bound. This yields a new estimate for the Lipschitz constant of a transport map pushing forward the standard Gaussian to a measure in this class. On the other hand, we show that assuming only fast decay of the tails of the initial datum does not suffice to guarantee uniform log-Hessian upper bounds.}, author = {Brigati, Giovanni and Pedrotti, Francesco}, issn = {1083-589X}, journal = {Electronic Communications in Probability}, publisher = {Institute of Mathematical Statistics}, title = {{Heat flow, log-concavity, and Lipschitz transport maps}}, doi = {10.1214/25-ECP717}, volume = {30}, year = {2025}, } @article{20050, abstract = {We prove upper bounds on the L∞-Wasserstein distance from optimal transport between strongly log-concave probability densities and log-Lipschitz perturbations. In the simplest setting, such a bound amounts to a transport-information inequality involving the L∞-Wasserstein metric and the relative L∞-Fisher information. We show that this inequality can be sharpened significantly in situations where the involved densities are anisotropic. Our proof is based on probabilistic techniques using Langevin dynamics. As an application of these results, we obtain sharp exponential rates of convergence in Fisher’s infinitesimal model from quantitative genetics, generalising recent results by Calvez, Poyato, and Santambrogio in dimension 1 to arbitrary dimensions.}, author = {Khudiakova, Kseniia and Maas, Jan and Pedrotti, Francesco}, issn = {1050-5164}, journal = {The Annals of Applied Probability}, number = {3}, pages = {1913--1940}, publisher = {Institute of Mathematical Statistics}, title = {{L∞-optimal transport of anisotropic log-concave measures and exponential convergence in Fisher’s infinitesimal model}}, doi = {10.1214/25-aap2162}, volume = {35}, year = {2025}, } @unpublished{22807, abstract = {Cleavage - the series of rapid cell divisions that follow fertilization - marks the onset of metazoan development and represents a deeply conserved evolutionary process. Across animals, two principal modes exist: complete (holoblastic) and incomplete (meroblastic) cleavage. While holoblastic cleavage resembles conventional cytokinesis both in vitro and in vivo, the mechanisms underlying meroblastic cleavage have remained poorly understood. Using zebrafish embryos as a model, we show that meroblastic cleavage proceeds through a distinct two-step mechanism. The process begins with the assembly and contraction of a large, arc-shaped actomyosin cable. However, this contractile event alone is insufficient to complete division. A second phase, driven by cadherin-mediated membrane adhesion, is required to invaginate the furrow ridge. Strikingly, this transition depends on mechanical uncoupling of the contractile cable from the surrounding cortex. We demonstrate that such uncoupling arises from an active nematic instability, which both enhances contractility along the cable and generates actin depletion zones that relieve lateral connections. Together, these findings reveal that meroblastic cleavage is governed not by a single actomyosin-based event but by a sequential interplay between cytoskeletal contraction and cadherin-dependent adhesion, highlighting a mechanism fundamentally distinct from canonical cytokinesis.}, author = {Tong, Xin and Li, Yuting I and Schelle, Joséphine and Hannezo, Edouard B and Heisenberg, Carl-Philipp J}, booktitle = {bioRxiv}, title = {{Non-canonical cytokinesis driven by mechanical uncoupling via nematic flows and adhesion-based invagination}}, doi = {10.1101/2025.10.15.682552}, year = {2025}, } @article{20705, abstract = {Optical tweezers are widely used as a highly sensitive tool to measure forces on micron-scale particles. One such application is the measurement of the electric charge of a particle, which can be done with high precision in liquids, air, or vacuum. We experimentally investigate how the trapping laser itself can electrically charge such a particle, in our case a ∼1  μ⁢m SiO2 sphere in air. We model the charging mechanism as a two-photon process which reproduces the experimental data with high fidelity.}, author = {Stöllner, Andrea and Lenton, Isaac C and Volosniev, Artem and Millen, James and Shibuya, Renjiro and Ishii, Hisao and Rak, Dmytro and Alpichshev, Zhanybek and David, Grégory and Signorell, Ruth and Muller, Caroline J and Waitukaitis, Scott R}, issn = {1079-7114}, journal = {Physical Review Letters}, number = {21}, publisher = {American Physical Society}, title = {{Using optical tweezers to simultaneously trap, charge, and measure the charge of a microparticle in air}}, doi = {10.1103/5xd9-4tjj}, volume = {135}, year = {2025}, } @phdthesis{20415, author = {Lee, Seungho}, issn = {2663-337X}, pages = {144}, publisher = {Institute of Science and Technology Austria}, title = {{Nanoparticle-based precursors toward advanced crystalline inorganic solids}}, doi = {10.15479/AT-ISTA-20415}, year = {2025}, } @unpublished{19399, abstract = {Phytohormone auxin and its directional transport mediate much of the remarkably plastic development of higher plants. Positive feedback between auxin signaling and transport is a key prerequisite for (i) self-organizing processes including vascular tissue formation and (ii) directional growth responses such as gravitropism. Here we identify a mechanism, by which auxin signaling directly targets PIN auxin transporters. Via the cell-surface ABP1-TMK1 receptor module, auxin rapidly induces phosphorylation and thus stabilization of PIN2. Following gravistimulation, initial auxin asymmetry activates autophosphorylation of the TMK1 kinase. This induces TMK1 interaction with and phosphorylation of PIN2, stabilizing PIN2 at the lower root side, thus reinforcing asymmetric auxin flow for root bending. Upstream of TMK1 in this regulation, ABP1 acts redundantly with the root-expressed ABP1-LIKE auxin receptor ABL3. Such positive feedback between cell-surface auxin signaling and PIN-mediated polar auxin transport is fundamental for robust root gravitropism and presumably also for other self-organizing developmental phenomena.}, author = {Rodriguez Solovey, Lesia and Fiedler, Lukas and Zou, Minxia and Giannini, Caterina and Monzer, Aline and Vladimirtsev, Dmitrii and Randuch, Marek and Yu, Yongfan and Gelová, Zuzana and Verstraeten, Inge and Hajny, Jakub and Chen, Meng and Tan, Shutang and Hörmayer, Lukas and Li, Lanxin and Marques-Bueno, Maria Mar and Quddoos, Zainab and Molnar, Gergely and Xu, Tongda and Kulich, Ivan and Jaillais, Yvon and Friml, Jiří}, booktitle = {bioRxiv}, title = {{ABP1/ABL3-TMK1 cell-surface auxin signaling directly targets PIN2-mediated auxin fluxes for root gravitropism}}, doi = {10.1101/2022.11.30.518503}, year = {2025}, } @phdthesis{20364, author = {Giannini, Caterina}, issn = {2663-337X}, keywords = {Auxin Signaling, Plant Development}, pages = {151}, publisher = {Institute of Science and Technology Austria}, title = {{Nuclear and cell surface auxin signaling in A. thaliana developmental transitions}}, doi = {10.15479/AT-ISTA-20364}, year = {2025}, } @phdthesis{20393, author = {Kishi, Kasumi}, issn = {2663-337X}, pages = {102}, publisher = {Institute of Science and Technology Austria}, title = {{Regulation of notochord and floor plate size during mouse development}}, doi = {10.15479/AT-ISTA-20393}, year = {2025}, } @article{20187, abstract = {Very long-chain fatty acids (VLCFAs), being constituents of different types of lipids, are critical factors in plant development, presumably due to their impact on the endomembrane system. The VLCFAs are synthesized in the endoplasmic reticulum by a heterotetrameric enzymatic complex including β-ketoacyl CoA reductase 1 (KCR1), whose mutant is lethal. Here, we describe the ectopic shoot meristems (esm) mutant, a viable kcr1 allele presumably affecting surface properties of the KCR1 protein. This kcr1-2 mutant shows reduced fatty acyl elongation that impacts VLCFAs. The kcr1-2 plants show severe defects during different stages of development, which all correlate with defects in polar localization and subcellular trafficking of PIN auxin transporters and resulting asymmetric auxin distribution. Detailed analysis of KCR1 expression and patterning defects in kcr1-2 suggests that KCR1 plays a role in delineating boundaries around meristematic and specialized differentiating tissues, including root and shoot meristems, initiating lateral roots, lateral root primordia, and trichomes. In these contexts, KCR1-produced VLCFAs may act in a non-cell-autonomous manner. Viable kcr1-2 represents a useful tool to study VLCFA roles in plant development and highlights VLCFAs as critical developmental factors at the interface of cell polarity and tissue development.}, author = {Babic, David and Abualia, Rashed and Fiedler, Lukas and Qi, Linlin and Tellier, Frédérique and Smoljan, Adrijana and Rakusova, Hana and Valošek, Petr and Han, Huibin and Benková, Eva and Faure, Jean Denis and Friml, Jiří}, issn = {1365-313X}, journal = {Plant Journal}, number = {3}, publisher = {Wiley}, title = {{Biosynthesis of very long-chain fatty acids is required for Arabidopsis auxin-mediated embryonic and post-embryonic development}}, doi = {10.1111/tpj.70396}, volume = {123}, year = {2025}, } @phdthesis{20362, author = {Babic, David}, issn = {2663-337X}, pages = {116}, publisher = {Institute of Science and Technology Austria}, title = {{Mechanisms of auxin-mediated early embryogenesis in Arabidopsis thaliana}}, doi = {10.15479/AT-ISTA-20362}, year = {2025}, } @unpublished{21427, abstract = {While tumor malignancy has been extensively studied under the prism of genetic and epigenetic heterogeneity, tumor cell states also critically depend on reciprocal interactions with the microenvironment. This raises the hitherto untested possibility that heterogeneity of the untransformed tumor stroma can actively fuel malignant progression. As biological heterogeneity is inherently difficult to control, we adopted a reductionist approach and let tumor cells invade micro-engineered environments harboring obstacles with precision-controlled geometry. We find that not only the presence of obstacles, but more surprisingly their spatial disorder, causes a drastic shift from a collective to a single-cell mode of invasion – comparable in strength to cadherin loss. Combining live-imaging and perturbation experiments with minimal biophysical modeling, we demonstrate that cell detachments result both from local geometrical constraints and a global integration of spatial disorder over time. We show that different types of microenvironments map onto different universality classes of invasion dynamics - homogeneous substrates follow Kardar–Parisi–Zhang (KPZ) scaling, while disordered ones exhibit exponents consistent with KPZ with quenched disorder (KPZq). Our findings highlight generic physical principles for how the mode of cancer cell invasion depends on environmental heterogeneity, with potential implications to understand tumor evolution in vivo.}, author = {Dunajova, Zuzana and Tasciyan, Saren and Majek, Juraj and Merrin, Jack and Sahai, Erik and Sixt, Michael K and Hannezo, Edouard B}, booktitle = {bioRxiv}, title = {{Substrate heterogeneity promotes cancer cell dissemination through interface roughening}}, doi = {10.1101/2025.05.20.655037}, year = {2025}, } @phdthesis{20798, abstract = {Atom interferometers measure the relative phase shifts between coherent matter-wave paths that arise from interactions with external fields or inertial forces. Due to their exceptional phase sensitivity, atom interferometers became an essential tool for precision measurements and fundamental physics experiments, finding applications in geodesy, gravimetry, and inertial navigation. However, their measurement precision is limited by quantum projection noise, which arises from the Heisenberg uncertainty principle, preventing the measurement of atomic states with absolute precision. The generation of entanglement between the atoms offers a path to surpass this so-called standard quantum limit, thereby enhancing the interferometer’s phase sensitivity beyond classical measurement bounds. This thesis reports on the development of an atom interferometer experiment designed to realize cavity-mediated, squeezed Mach-Zehnder-type interferometry with ultra-cold 87Rb atoms. The experiment combines cavity-aided spin-squeezing with cavity-mediated Mach-Zehnder interferometry to demonstrate entanglement-enhanced phase sensitivity. The experiment is centered on a triangular optical cavity that mediates all relevant atom-light interactions. The cavity provides optical trapping, spin-squeezing, and Raman beam-splitter operations, enabling to perform interferometry on a continuously trapped atomic ensemble. The thesis elaborates on the fundamental theoretical framework, the cavity design, and the full optical setup, including the detailed configuration of the developed laser stabilization methods. Experimentally, continuous loading methods were explored, resulting in an accumulation of up to 4 × 106 atoms in the dipole trap within a cycle time of 500 ms. The AC Stark shift compensation method developed for continuous loading was further applied for in-trap cooling to 10 µK, and optical pumping for efficient atomic state preparation. Coherent state control was verified via observation of microwave-driven Rabi oscillations, and used to characterize atom-cavity coupling. These presented results establish the experimental groundwork for the future development of cavity-mediated, entanglement-enhanced Mach-Zehnder-type atom interferometry.}, author = {Wald, Sebastian}, isbn = {978-3-99078-075-6}, issn = {2663-337X}, keywords = {entanglement-enhanced atom interferometry, cavity QED, spin-squeezing, dipole trap, quantum optics}, pages = {152}, publisher = {Institute of Science and Technology Austria}, title = {{Atoms in a propagating-wave cavity for squeezed Mach-Zehnder atom interferometry}}, doi = {10.15479/AT-ISTA-20798}, year = {2025}, } @article{19498, abstract = {A dynamic interplay between fast synaptic signals and slower neuromodulatory signals controls the excitatory/inhibitory (E/I) balance within neuronal circuits. The mechanisms by which neuropeptide signaling is regulated to maintain E/I balance remain uncertain. We designed a genetic screen to isolate genes involved in the peptidergic maintenance of the E/I balance in the C. elegans motor circuit. This screen identified the C. elegans orthologs of the presynaptic phosphoprotein synapsin (snn-1) and the protein phosphatase 1 (PP1) regulatory subunit PHACTR1 (phac-1). We demonstrate that both phac-1 and snn-1 alter the motor behavior of C. elegans, and genetic interactions suggest that SNN-1 contributes to PP1-PHAC-1 holoenzyme signaling. De novo variants of human PHACTR1, associated with early-onset epilepsies [developmental and epileptic encephalopathy 70 (DEE70)], when expressed in C. elegans resulted in constitutive PP1-PHAC-1 holoenzyme activity. Unregulated PP1-PHAC-1 signaling alters the synapsin and actin cytoskeleton and increases neuropeptide release by cholinergic motor neurons, which secondarily affects the presynaptic vesicle cycle. Together, these results clarify the dominant mechanisms of action of the DEE70 alleles and suggest that altered neuropeptide release may alter E/I balance in DEE70.}, author = {Stratigi, Aikaterini and Soler-García, Miguel and Krout, Mia and Shukla, Shikha and De Bono, Mario and Richmond, Janet E. and Laurent, Patrick}, issn = {1529-2401}, journal = {Journal of Neuroscience}, number = {13}, publisher = {Society for Neuroscience}, title = {{Neuroendocrine control of synaptic transmission by PHAC-1 in C. elegans}}, doi = {10.1523/JNEUROSCI.1767-23.2024}, volume = {45}, year = {2025}, } @phdthesis{18871, abstract = {"Can we do this with a new type of computer - a quantum computer?". This famous quotation of the brilliant Richard Feynman within a conference talk on "Simulating physics with computers.” is often reverently praised as the origin of the field of quantum computing. The idea was to use quantum mechanical systems itself to simulate "Nature", which is inherently quantum mechanical. Now, 43 years later, the theoretical framework of how such a computer can operate has been developed. Two main important concepts for a potential quantum supremacy, superposition and entanglement, have been exploited to design quantum algorithms to significantly speed up certain tasks. Yet, the specific hardware implementation is still far from being certain, in fact the race between the most promising platforms such as superconducting qubits, bosonic codes, cold atoms, trapped ions, optical computing as well as spin qubits has recently intensified. If one also includes the most mature applications of quantum communication technologies, secure quantum key distribution and quantum random number generators, as part of a quantum information technology ecosystem, we are confronted with a plethora of different materials, concepts, and also operation frequencies. While superconducting qubits, bosonic codes and spin qubits work in the regime of approximately 5 GHz and are controlled by electrical fields, trapped ions, cold atoms, and optical quantum computing operate with light in the infrared or visible range. Consequently, a quantum frequency converter or microwave-optic transducer is required to interface the different frequency domains or establish a long-range network connection with suitable telecom fibers. In fact, the combination of different frequency regimes is also an essential part in our classical modern communication network, where computations are performed in electrical circuits and the information exchange over longer distances happens via optical fibers. However, the specific challenges specific to building a quantum computer, also apply to the development of such a quantum frequency transducer: 1) As we deal with single excitations as the carrier of information, i.e. the smallest possible quantity, the signal can easily be corrupted by other noise sources which needs to be avoided by all means. This is also the reason why microwave quantum computers operate at temperature environments close to zero temperature (< 0.1 Kelvin) to avoid corruption by thermal noise. 2) The frequency interface generally needs to preserve the phase of the signal as an essential part of the quantum state. And 3) Quantum signals cannot be copied which would be a typical strategy to account for errors in classical computers. And finally, there is a challenge specific to microwave-optic transducers: While quantum computers are operating in one specific frequency domain, microwave-optic transducers combine microwave and optical fields in one device. This results in the particular challenge that high-energy optical radiation, which is usually well-shielded from superconducting microwave quantum processors, are now an essential part of the device. The concomitant optical radiation in the operating transducer will inevitably have a detrimental effect on the superconducting microwave components. Together with the requirement of minimal background noise for quantum-limited operation as described above, v heating from the absorption of optical photons within the same device where single microwave excitations are processed forms a formidable challenge. This thesis aims to address this challenge by developing microwave-optic transducers where the impact of optical absorption on superconducting circuits in general and superconducting qubits specifically can be mitigated. In our first approach, we developed a compact device with optimized interaction strengths between the different frequency domains. This minimizes the optical powers used for transducer operation and thus the optical absorption heating. This work was - to the best of our knowledge - the first comprehensive noise study, in an integrated microwave-optic transducer. Unfortunately, we saw that the optical absorption heating added noise way above a single excitation. Consequently, a potential quantum signal would have been buried in the noise, added by the transduction. Building on this insight, we utilized a three-dimensional microwave-optic transducer instead of an integrated device. The larger heat capacity of the macroscopic device with a size of a few millimeters can absorb a larger fraction of the optical heating before it increases the temperature of the device. This allowed us to interface the transducer directly with a superconducting qubit to readout the qubit state in a novel all-optical manner. We showed that the microwave-optic transducer can be operated in a regime in which optical fields don’t harm the sensitive qubit. This is an important prerequisite for the operation of microwave-optic transducers in conjunction with microwave quantum processors and brings the integration and seamless orchestration of different frequency components in a quantum network a step closer. }, author = {Arnold, Georg M}, issn = {2663-337X}, pages = {135}, publisher = {Institute of Science and Technology Austria}, title = {{Microwave-optic interconnects for superconducting circuits}}, doi = {10.15479/at:ista:18871}, year = {2025}, } @phdthesis{19745, abstract = {Cell migration is a crucial process in animal development and maintenance. It is incredibly heterogeneous, with different cell types utilizing fundamentally distinct migration strategies. The strategies also depend on the cellular microenvironment, where cells can switch between migration modes as they encounter new environmental cues. In this thesis, we investigated how dendritic cells adapt their migration strategy when encountering geometrically, mechanically and chemically distinct environments. When dendritic cells are embedded in a homogeneous fibrous network, they migrate in a fast and directional amoeboid manner. In this migration strategy, extracellular proteolysis and integrin-mediated adhesions are dispensable. Instead, the cells use topography of the environment to propel their cell body forward. To migrate efficiently in the maze of different pore sizes, they position the nucleus ahead of the microtubule organizing center (MTOC) and use it to gauge the pores to identify the path of least resistance. Our aim was to identify whether dendritic cells adapt their migration strategy when encountering asymmetrical transitions into much denser environments with limited choice of large pores. In such invasive transitions it is unclear if the cells can cross tight pores without the use of adhesions and extracellular proteolysis and whether they maintain the nucleus in the cell front. Using various cell migration assays such as fibrous 3D collagen gels, geometrically defined microchannels with constrictions and simplistic under agarose migration assay, we provide a comprehensive characterization of invasive migration of dendritic cells. We show that during invasion the cells stall and stretch, reflecting the difficulty to translocate the bulky cell body into the dense environment. In collagen gels, we show that dendritic cells can invade without proteolysis and adhesions. Instead, they utilize contractility, which can lead to largescale collagen compressions. During invasion, the nucleus stalls at tight constrictions, leading to a transient organelle reorientation. To resolve the stalling, upregulated rear contractility is required. This contractile force is simultaneously necessary for reverting the nucleus back to the cell front after invasion and maintaining this positioning during permissive migration. A functional role of the reorientation was uncovered in the first collaboration project. A prominent central actin pool was identified around the MTOC, especially pronounced in dense and compressive environments. The actin pool was shown to generate pushing forces to dilate the space for cell translocation. These forces are only necessary in non-permissive environments, where the nucleus reorients to the cell rear, allowing the actin pool to generate space. In permissive environments where space generation is dispensable, the MTOC is located behind the nucleus and the actin cloud has reduced intensity, allowing more actin to be incorporated into the lamellipodium, speeding up migration. In the second collaboration project, we investigated the effects of distinct chemical environments on dendritic cell migration. The strikingly persistent migration of these cells was explained by their ability to modulate and even self-generate chemokine gradients. This allows the cells to migrate faster and more persistent in uniform chemokine fields compared to imposed chemokine gradients. The chemokine receptor CCR7 was identified as a crucial player in this process, both sensing the signal and internalizing the chemokine to create a sink.}, author = {Canigova, Nikola}, isbn = {978-3-99078-058-9}, issn = {2663-337X}, pages = {133}, publisher = {Institute of Science and Technology Austria}, title = {{Adaptive strategies of dendritic cell migration in response to environmental cues}}, doi = {10.15479/AT-ISTA-19745}, year = {2025}, } @phdthesis{19271, abstract = {The medial habenula (MHb) is implicated in regulating emotional responses to aversive events. Studies in zebrafish have identified a remarkable morphological left-right asymmetry in the dorsal habenula (zebrafish equivalent of mammalian MHb)-to-interpeduncular nucleus (IPN) pathway and its left-side specific role in modulating fear responses. However, there is little evidence for structural or functional lateralization in the mammalian MHb-IPN pathway. Here, I investigated the synaptic properties of the left and right MHb afferents to the IPN in mice and addressed whether these synaptic connections selectively influence the expression of conditioned fear in mice. My findings reveal that each individual IPN neuron receives inputs from both left and right MHb. Electrophysiological recordings from the same postsynaptic IPN neurons demonstrate that the left MHb-originating synapses exhibit lower release probability and higher 𝛾-aminobutyric acid type B receptor (GABABR)-mediated potentiation compared to the right MHb-originating synapses. Interestingly, chemogenetic inhibition of cholinergic neurons in the left but not the right MHb significantly attenuated cue-dependent fear recall. Furthermore, conditional deletion of GABABR in the left MHb interfered with the recall of cued fear memory, whereas that in the right MHb neurons spared fear memory expression. Collectively, I demonstrate a functional asymmetry of the MHb in mice, revealing a predominant role for GABABR-mediated signaling in the left MHb-IPN pathway in the modulation of fear memories. These findings suggest that lateralized pathways could represent a fundamental principle in the neural regulation of emotion across species.}, author = {Önal, Hüseyin C}, issn = {2663-337X}, publisher = {Institute of Science and Technology Austria}, title = {{Asymmetrical modulation of fear expression via GABAB receptors in the mouse medial habenula}}, doi = {10.15479/AT-ISTA-19271}, year = {2025}, } @phdthesis{19431, abstract = {Gene expression is crucial for cell differentiation, development and survival of organisms. It consists of several steps, starting with transcription that is mediated by RNA polymerases. These are protein machineries transcribing and producing different types of RNAs. Although, the individual steps of transcription by RNA polymerase II (Pol II) as well as the structure of Pol II has been extensively studied, surprisingly, there is still little known about its regulation and assembly in cytoplasm. Among the proteins that are important in biogenesis of Pol II are RNA polymerase II associating proteins (RPAP) and small GPN-loop GTPases (GPN). Both of these protein groups were shown to take essential part in assembly of Pol II. The aim of this project was to deepen our knowledge in regulation of Pol II in the cytoplasm as well as the proteins involved in this process. Techniques of structural biology, biochemistry and cell biology were employed to study and characterize cytoplasmic Pol II and its interacting partners. This study shows for the first time the structure of cytoplasmic Pol II at high resolution. The structure also reveals proteins interacting with Pol II in cytoplasm, namely GDOWN1, RPAP2. Comparing the structure of cytoplasmic Pol II with transcribing Pol II revealed striking difference in clamp region that is not in closed state. Furthermore, GDOWN1 and RPAP2 make steric clashes with various transcription factors bound to Pol II during different stages of transcription. Even though GPN1 and GPN3 proteins were not resolved in the cytoplasmic Pol II structure, they are part of the complex and their interaction with Pol II was confirmed in vitro. RPAP2 stabilizes these proteins on Pol II and several experiments suggest that they interact with the clamp region. In addition, GDOWN1, RPAP2 and GPNs might keep clamp in open or partially open state. Based on these results I propose a novel model of regulation of Pol II in cytoplasm. GDOWN1, RPAP2, GPN1 and GPN3 bind to Pol II in cytoplasm and doing so they can prevent pre-mature binding of DNA or RNA and different transcription factors to Pol II in cytoplasm or before engaging in transcription nucleus. This research contributes to the current knowledge of molecular mechanisms of Pol II regulation in cytoplasm.}, author = {Hlavata, Annamaria}, isbn = {978-3-99078-055-8}, issn = {2663-337X}, pages = {83}, publisher = {Institute of Science and Technology Austria}, title = {{Regulation of Cytoplasmic RNA Polymerase II}}, doi = {10.15479/10.15479/AT-ISTA-19431}, year = {2025}, }