@article{12521,
  abstract     = {Differentiated X chromosomes are expected to have higher rates of adaptive divergence than autosomes, if new beneficial mutations are recessive (the “faster-X effect”), largely because these mutations are immediately exposed to selection in males. The evolution of X chromosomes after they stop recombining in males, but before they become hemizygous, has not been well explored theoretically. We use the diffusion approximation to infer substitution rates of beneficial and deleterious mutations under such a scenario. Our results show that selection is less efficient on diploid X loci than on autosomal and hemizygous X loci under a wide range of parameters. This “slower-X” effect is stronger for genes affecting primarily (or only) male fitness, and for sexually antagonistic genes. These unusual dynamics suggest that some of the peculiar features of X chromosomes, such as the differential accumulation of genes with sex-specific functions, may start arising earlier than previously appreciated.},
  author       = {Mrnjavac, Andrea and Khudiakova, Kseniia and Barton, Nicholas H and Vicoso, Beatriz},
  issn         = {2056-3744},
  journal      = {Evolution Letters},
  keywords     = {Genetics, Ecology, Evolution, Behavior and Systematics},
  number       = {1},
  publisher    = {Oxford University Press},
  title        = {{Slower-X: Reduced efficiency of selection in the early stages of X chromosome evolution}},
  doi          = {10.1093/evlett/qrac004},
  volume       = {7},
  year         = {2023},
}

@phdthesis{14622,
  abstract     = {This Ph.D. thesis presents a detailed investigation into Variational Quantum Algorithms
(VQAs), a promising class of quantum algorithms that are well suited for near-term quantum
computation due to their moderate hardware requirements and resilience to noise. Our
primary focus lies on two particular types of VQAs: the Quantum Approximate Optimization
Algorithm (QAOA), used for solving binary optimization problems, and the Variational Quantum
Eigensolver (VQE), utilized for finding ground states of quantum many-body systems.
In the first part of the thesis, we examine the issue of effective parameter initialization for
the QAOA. The work demonstrates that random initialization of the QAOA often leads to
convergence in local minima with sub-optimal performance. To mitigate this issue, we propose
an initialization of QAOA parameters based on the Trotterized Quantum Annealing (TQA).
We show that TQA initialization leads to the same performance as the best of an exponentially
scaling number of random initializations.
The second study introduces Transition States (TS), stationary points with a single direction
of descent, as a tool for systematically exploring the QAOA optimization landscape. This
leads us to propose a novel greedy parameter initialization strategy that guarantees for the
energy to decrease with increasing number of circuit layers.
In the third section, we extend the QAOA to qudit systems, which are higher-dimensional
generalizations of qubits. This chapter provides theoretical insights and practical strategies for
leveraging the increased computational power of qudits in the context of quantum optimization
algorithms and suggests a quantum circuit for implementing the algorithm on an ion trap
quantum computer.
Finally, we propose an algorithm to avoid “barren plateaus”, regions in parameter space with
vanishing gradients that obstruct efficient parameter optimization. This novel approach relies
on defining a notion of weak barren plateaus based on the entropies of local reduced density
matrices and showcases how these can be efficiently quantified using shadow tomography.
To illustrate the approach we employ the strategy in the VQE and show that it allows to
successfully avoid barren plateaus in the initialization and throughout the optimization.
Taken together, this thesis greatly enhances our understanding of parameter initialization and
optimization in VQAs, expands the scope of QAOA to higher-dimensional quantum systems,
and presents a method to address the challenge of barren plateaus using the VQE. These
insights are instrumental in advancing the field of near-term quantum computation.},
  author       = {Sack, Stefan},
  issn         = {2663-337X},
  pages        = {142},
  publisher    = {Institute of Science and Technology Austria},
  title        = {{Improving variational quantum algorithms : Innovative initialization techniques and extensions to qudit systems}},
  doi          = {10.15479/at:ista:14622},
  year         = {2023},
}

@article{13125,
  abstract     = {The quantum approximate optimization algorithm (QAOA) is a variational quantum algorithm, where a quantum computer implements a variational ansatz consisting of p layers of alternating unitary operators and a classical computer is used to optimize the variational parameters. For a random initialization, the optimization typically leads to local minima with poor performance, motivating the search for initialization strategies of QAOA variational parameters. Although numerous heuristic initializations exist, an analytical understanding and performance guarantees for large p remain evasive.We introduce a greedy initialization of QAOA which guarantees improving performance with an increasing number of layers. Our main result is an analytic construction of 2p + 1 transition states—saddle points with a unique negative curvature direction—for QAOA with p + 1 layers that use the local minimum of QAOA with p layers. Transition states connect to new local minima, which are guaranteed to lower the energy compared to the minimum found for p layers. We use the GREEDY procedure to navigate the exponentially increasing with p number of local minima resulting from the recursive application of our analytic construction. The performance of the GREEDY procedure matches available initialization strategies while providing a guarantee for the minimal energy to decrease with an increasing number of layers p. },
  author       = {Sack, Stefan and Medina Ramos, Raimel A and Kueng, Richard and Serbyn, Maksym},
  issn         = {2469-9934},
  journal      = {Physical Review A},
  number       = {6},
  publisher    = {American Physical Society},
  title        = {{Recursive greedy initialization of the quantum approximate optimization algorithm with guaranteed improvement}},
  doi          = {10.1103/physreva.107.062404},
  volume       = {107},
  year         = {2023},
}

@phdthesis{14697,
  abstract     = {During my Ph.D. research, I managed a series of projects, each focused on the
mechanisms underlying cell migration. My work involved an in-depth examination of
the complex strategies employed by neutrophils, with a specific focus on their ability to
synchronize spatial-temporal cues and optimize their gradient perception. However, it
is essential to acknowledge that not all projects yielded successful results, as some
ideas were discontinued and are archived for future reference within this thesis.
My main project investigated how neutrophils decode spatial cues for precise navigation. Human neutrophils showcased distinct movement patterns based on source
type – linear or point-like. By combining single-cell tracking in 3D environments with
proxy dyes, this project linked cell behaviors to gradient changes, revealing a stronger
response to semi-exponential gradients from point sources. In addition, neutrophils
exhibited oscillating migration speeds, using speed minima to adjust trajectories toward sources. Experiencing continuous concentration changes, they accelerated over
time and employed a "Run and Fumble" strategy, alternating between consistent runs
and strategic "tumbles" for efficient navigation.
The project extended to the possibility of cells amplifying perceived gradients by
enclosing their immediate surroundings, pushing attractants forward for enrichment
while depleting it at the cell rear. Microfluidic devices were employed, and various experimental parameters configurations were optimized. Although significant differences
in migratory efficacy were detected across pore sizes and device heights, quantifying
gradient manipulation effects proved challenging.
The "Laser-Assisted Protein Adsorption by Photobleaching" (LAPAP) project was
promising, as it allowed the printing of gradients. Initially successful with dendritic cells,
we aimed to adapt it for neutrophils. Through extensive experimentation with multiple
parameters, we attempted to trigger responses from neutrophils. Despite these efforts
and collaboration, the project failed due to practical challenges and limitations.
Facing a lack of neutrophil-like cells at IST, we initially established the SCF-HoxB8
primary murine cell line. Despite their existence, their migratory behavior was largely
unexplored due to potential limitations. Through differentiation protocol refinements we
enhanced their migratory capabilities, though their capacity still lagged behind human
neutrophils. Despite this, the improved migration potential of these cells pointed toward
their utility for in vitro murine neutrophil migration studies.},
  author       = {Stopp, Julian A},
  isbn         = {978-3-99078-038-1},
  issn         = {2663-337X},
  pages        = {226},
  publisher    = {Institute of Science and Technology Austria},
  title        = {{Neutrophils on the hunt : Migratory strategies employed by neutrophils to fulfill their effector function}},
  doi          = {10.15479/at:ista:14697},
  year         = {2023},
}

@article{14274,
  abstract     = {Immune responses rely on the rapid and coordinated migration of leukocytes. Whereas it is well established that single-cell migration is often guided by gradients of chemokines and other chemoattractants, it remains poorly understood how these gradients are generated, maintained, and modulated. By combining experimental data with theory on leukocyte chemotaxis guided by the G protein–coupled receptor (GPCR) CCR7, we demonstrate that in addition to its role as the sensory receptor that steers migration, CCR7 also acts as a generator and a modulator of chemotactic gradients. Upon exposure to the CCR7 ligand CCL19, dendritic cells (DCs) effectively internalize the receptor and ligand as part of the canonical GPCR desensitization response. We show that CCR7 internalization also acts as an effective sink for the chemoattractant, dynamically shaping the spatiotemporal distribution of the chemokine. This mechanism drives complex collective migration patterns, enabling DCs to create or sharpen chemotactic gradients. We further show that these self-generated gradients can sustain the long-range guidance of DCs, adapt collective migration patterns to the size and geometry of the environment, and provide a guidance cue for other comigrating cells. Such a dual role of CCR7 as a GPCR that both senses and consumes its ligand can thus provide a novel mode of cellular self-organization.},
  author       = {Alanko, Jonna H and Ucar, Mehmet C and Canigova, Nikola and Stopp, Julian A and Schwarz, Jan and Merrin, Jack and Hannezo, Edouard B and Sixt, Michael K},
  issn         = {2470-9468},
  journal      = {Science Immunology},
  keywords     = {General Medicine, Immunology},
  number       = {87},
  publisher    = {American Association for the Advancement of Science},
  title        = {{CCR7 acts as both a sensor and a sink for CCL19 to coordinate collective leukocyte migration}},
  doi          = {10.1126/sciimmunol.adc9584},
  volume       = {8},
  year         = {2023},
}

@article{14360,
  abstract     = {To navigate through diverse tissues, migrating cells must balance persistent self-propelled motion with adaptive behaviors to circumvent obstacles. We identify a curvature-sensing mechanism underlying obstacle evasion in immune-like cells. Specifically, we propose that actin polymerization at the advancing edge of migrating cells is inhibited by the curvature-sensitive BAR domain protein Snx33 in regions with inward plasma membrane curvature. The genetic perturbation of this machinery reduces the cells’ capacity to evade obstructions combined with faster and more persistent cell migration in obstacle-free environments. Our results show how cells can read out their surface topography and utilize actin and plasma membrane biophysics to interpret their environment, allowing them to adaptively decide if they should move ahead or turn away. On the basis of our findings, we propose that the natural diversity of BAR domain proteins may allow cells to tune their curvature sensing machinery to match the shape characteristics in their environment.},
  author       = {Sitarska, Ewa and Almeida, Silvia Dias and Beckwith, Marianne Sandvold and Stopp, Julian A and Czuchnowski, Jakub and Siggel, Marc and Roessner, Rita and Tschanz, Aline and Ejsing, Christer and Schwab, Yannick and Kosinski, Jan and Sixt, Michael K and Kreshuk, Anna and Erzberger, Anna and Diz-Muñoz, Alba},
  issn         = {2041-1723},
  journal      = {Nature Communications},
  publisher    = {Springer Nature},
  title        = {{Sensing their plasma membrane curvature allows migrating cells to circumvent obstacles}},
  doi          = {10.1038/s41467-023-41173-1},
  volume       = {14},
  year         = {2023},
}

@phdthesis{14280,
  abstract     = {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.},
  author       = {Radler, Philipp},
  isbn         = {978-3-99078-033-6},
  issn         = {2663-337X},
  keywords     = {Cell Division, Reconstitution, FtsZ, FtsA, Divisome, E.coli},
  pages        = {156},
  publisher    = {Institute of Science and Technology Austria},
  title        = {{Spatiotemporal signaling during assembly of the bacterial divisome}},
  doi          = {10.15479/at:ista:14280},
  year         = {2023},
}

@article{12349,
  abstract     = {Statistics of natural scenes are not uniform - their structure varies dramatically from ground to sky. It remains unknown whether these non-uniformities are reflected in the large-scale organization of the early visual system and what benefits such adaptations would confer. Here, by relying on the efficient coding hypothesis, we predict that changes in the structure of receptive fields across visual space increase the efficiency of sensory coding. We show experimentally that, in agreement with our predictions, receptive fields of retinal ganglion cells change their shape along the dorsoventral retinal axis, with a marked surround asymmetry at the visual horizon. Our work demonstrates that, according to principles of efficient coding, the panoramic structure of natural scenes is exploited by the retina across space and cell-types.},
  author       = {Gupta, Divyansh and Mlynarski, Wiktor F and Sumser, Anton L and Symonova, Olga and Svaton, Jan and Jösch, Maximilian A},
  issn         = {1546-1726},
  journal      = {Nature Neuroscience},
  pages        = {606--614},
  publisher    = {Springer Nature},
  title        = {{Panoramic visual statistics shape retina-wide organization of receptive fields}},
  doi          = {10.1038/s41593-023-01280-0},
  volume       = {26},
  year         = {2023},
}

@misc{12370,
  abstract     = {Statistics of natural scenes are not uniform - their structure varies dramatically from ground to sky. It remains unknown whether these non-uniformities are reflected in the large-scale organization of the early visual system and what benefits such adaptations would confer. Here, by relying on the efficient coding hypothesis, we predict that changes in the structure of receptive fields across visual space increase the efficiency of sensory coding. We show experimentally that, in agreement with our predictions, receptive fields of retinal ganglion cells change their shape along the dorsoventral retinal axis, with a marked surround asymmetry at the visual horizon. Our work demonstrates that, according to principles of efficient coding, the panoramic structure of natural scenes is exploited by the retina across space and cell-types. },
  author       = {Gupta, Divyansh and Sumser, Anton L and Jösch, Maximilian A},
  publisher    = {Institute of Science and Technology Austria},
  title        = {{Research Data for: Panoramic visual statistics shape retina-wide organization of receptive fields}},
  doi          = {10.15479/AT:ISTA:12370},
  year         = {2023},
}

@phdthesis{12800,
  abstract     = {The evolutionary processes that brought about today’s plethora of living species and the many billions more ancient ones all underlie biology. Evolutionary pathways are neither directed nor deterministic, but rather an interplay between selection, migration, mutation, genetic drift and other environmental factors. Hybrid zones, as natural crossing experiments, offer a great opportunity to use cline analysis to deduce different evolutionary processes - for example, selection strength. Theoretical cline models, largely assuming uniform distribution of individuals, often lack the capability of incorporating population structure. Since in reality organisms mostly live in patchy distributions and their dispersal is hardly ever Gaussian, it is necessary to unravel the effect of these different elements of population structure on cline parameters and shape. In this thesis, I develop a simulation inspired by the A. majus hybrid zone of a single selected locus under frequency dependent selection. This simulation enables us to untangle the effects of different elements of population structure as for example a low-density center and long-range dispersal. This thesis is therefore a first step towards theoretically untangling the effects of different elements of population structure on cline parameters and shape. },
  author       = {Julseth, Mara},
  issn         = {2791-4585},
  pages        = {21},
  publisher    = {Institute of Science and Technology Austria},
  title        = {{The effect of local population structure on genetic variation at selected loci in the A. majus hybrid zone}},
  doi          = {10.15479/at:ista:12800},
  year         = {2023},
}

@phdthesis{12781,
  abstract     = {Most energy in humans is produced in form of ATP by the mitochondrial respiratory chain consisting of several protein assemblies embedded into lipid membrane (complexes I-V). Complex I is the first and the largest enzyme of the respiratory chain which is essential for energy production. It couples the transfer of two electrons from NADH to ubiquinone with proton translocation across bacterial or inner mitochondrial membrane. The coupling mechanism between electron transfer and proton translocation is one of the biggest enigma in bioenergetics and structural biology. Even though the enzyme has been studied for decades, only recent technological advances in cryo-EM allowed its extensive structural investigation. 

Complex I from E.coli appears to be of special importance because it is a perfect model system with a rich mutant library, however the structure of the entire complex was unknown. In this thesis I have resolved structures of the minimal complex I version from E. coli in different states including reduced, inhibited, under reaction turnover and several others. Extensive structural analyses of these structures and comparison to structures from other species allowed to derive general features of conformational dynamics and propose a universal coupling mechanism. The mechanism is straightforward, robust and consistent with decades of experimental data available for complex I from different species. 

Cyanobacterial NDH (cyanobacterial complex I) is a part of broad complex I superfamily and was studied as well in this thesis. It plays an important role in cyclic electron transfer (CET), during which electrons are cycled within PSI through ferredoxin and plastoquinone to generate proton gradient without NADPH production. Here, I solved structure of NDH and revealed additional state, which was not observed before. The novel “resting” state allowed to propose the mechanism of CET regulation. Moreover, conformational dynamics of NDH resembles one in complex I which suggest more broad universality of the proposed coupling mechanism.

In summary, results presented here helped to interpret decades of experimental data for complex I and contributed to fundamental mechanistic understanding of protein function.
},
  author       = {Kravchuk, Vladyslav},
  isbn         = {978-3-99078-029-9},
  issn         = {2663-337X},
  pages        = {127},
  publisher    = {Institute of Science and Technology Austria},
  title        = {{Structural and mechanistic study of bacterial complex I and its cyanobacterial ortholog}},
  doi          = {10.15479/at:ista:12781},
  year         = {2023},
}

@phdthesis{14510,
  abstract     = {Clathrin-mediated endocytosis (CME) is vital for the regulation of plant growth and
development by controlling plasma membrane protein composition and cargo uptake. CME
relies on the precise recruitment control of protein regulators for vesicle maturation and
release. During the early stages of endocytosis, an area of flat membrane is remodelled by
proteins to create a spherical vesicle against intracellular forces. After the Clathrin-coated
vesicle (CCV) is fully formed, scission machinery releases it from the plasma membrane,
and cargo proceeds for recycling or degradation through early endosomes / Trans Golgi
network. Protein machineries that mediate membrane bending and vesicle release in plants
are unknown. However, studies show, that plant endocytosis is actin independent, thus
indicating that plants utilize a unique mechanism to mediate membrane bending against highturgor pressure compared to other model systems. First, by using biochemical and advanced
live microscopy approaches we investigate the TPLATE complex, a plant-specific
endocytosis protein complex. We found that TPLATE is peripherally associated with
clathrin-coated vesicles and localises at the rim of endocytosis events. Next, our study of
plant Dynamin-related protein 1C (DRP1C), which was hypothesised previously to play a
role in vesicle release, shows the recruitment of the protein already at the early stages of
endocytosis. Moreover, DRP1C assembles into organised ring-like structures and is able to
induce membrane deformation and tubulation, suggesting its role also in membrane bending
during early CME. Based on the data from mammalian and yeast systems, plant DynaminRelated Proteins 2 and SH3P2 protein are strong candidates to be part of the plant vesicle
scission machinery; however, their precise role in plant CME has not been yet elucidated.
Here, we characterised DRP2s and SH3P2 roles in CME by combining high-resolution
imaging of endocytic events in vivo and protein characterisation. Although DRP2s and
SH3P2 arrive together during late CME and physically interact, genetic analysis using
∆sh3p1,2,3 mutant and complementation with non-DRP2-interacting SH3P2 variants suggest
that SH3P2 does not directly recruit DRP2s to the site of endocytosis. Summarising our
research, these observations provide new important insights into the mechanism of plant
CME and show that, despite plants posses many homologues of mammalian and yeast CME
components, they do not necessarily act in the same manner. },
  author       = {Gnyliukh, Nataliia},
  isbn         = {978-3-99078-037-4},
  issn         = {2663-337X},
  keywords     = {Clathrin-Mediated Endocytosis, vesicle scission, Dynamin-Related Protein 2, SH3P2, TPLATE complex, Total internal reflection fluorescence microscopy, Arabidopsis thaliana},
  pages        = {180},
  publisher    = {Institute of Science and Technology Austria},
  title        = {{Mechanism of clathrin-coated vesicle  formation during endocytosis in plants}},
  doi          = {10.15479/at:ista:14510},
  year         = {2023},
}

@unpublished{14591,
  abstract     = {Clathrin-mediated endocytosis (CME) is vital for the regulation of plant growth and development by controlling plasma membrane protein composition and cargo uptake. CME relies on the precise recruitment of regulators for vesicle maturation and release. Homologues of components of mammalian vesicle scission are strong candidates to be part of the scissin machinery in plants, but the precise roles of these proteins in this process is not fully understood. Here, we characterised the roles of Plant Dynamin-Related Proteins 2 (DRP2s) and SH3-domain containing protein 2 (SH3P2), the plant homologue to Dynamins’ recruiters, like Endophilin and Amphiphysin, in the CME by combining high-resolution imaging of endocytic events in vivo and characterisation of the purified proteins in vitro. Although DRP2s and SH3P2 arrive similarly late during CME and physically interact, genetic analysis of the Dsh3p1,2,3 triple-mutant and complementation assays with non-SH3P2-interacting DRP2 variants suggests that SH3P2 does not directly recruit DRP2s to the site of endocytosis. These observations imply that despite the presence of many well-conserved endocytic components, plants have acquired a distinct mechanism for CME. One Sentence Summary In contrast to predictions based on mammalian systems, plant Dynamin-related proteins 2 are recruited to the site of Clathrin-mediated endocytosis independently of BAR-SH3 proteins.},
  author       = {Gnyliukh, Nataliia and Johnson, Alexander J and Nagel, Marie-Kristin and Monzer, Aline and Hlavata, Annamaria and Isono, Erika and Loose, Martin and Friml, Jiří},
  booktitle    = {bioRxiv},
  title        = {{Role of dynamin-related proteins 2 and SH3P2 in clathrin-mediated endocytosis in plants}},
  doi          = {10.1101/2023.10.09.561523},
  year         = {2023},
}

@phdthesis{14226,
  abstract     = {We introduce the notion of a Faustian interchange in a 1-parameter family of smooth
functions to generalize the medial axis to critical points of index larger than 0.
We construct and implement a general purpose algorithm for approximating such
generalized medial axes.},
  author       = {Stephenson, Elizabeth R},
  issn         = {2791-4585},
  pages        = {43},
  publisher    = {Institute of Science and Technology Austria},
  title        = {{Generalizing medial axes with homology switches}},
  doi          = {10.15479/at:ista:14226},
  year         = {2023},
}

@phdthesis{12470,
  abstract     = {The brain is an exceptionally sophisticated organ consisting of billions of cells and trillions of 
connections that orchestrate our cognition and behavior. To decode its complex connectivity, it is 
pivotal to disentangle its intricate architecture spanning from cm-sized circuits down to tens of 
nm-small synapses.
To achieve this goal, I developed CATS – Comprehensive Analysis of nervous Tissue across 
Scales, a versatile toolbox for obtaining a holistic view of nervous tissue context with (superresolution) fluorescence microscopy. CATS combines comprehensive labeling of the extracellular
space, that is compatible with chemical fixation, with information on molecular markers, superresolved data acquisition and machine-learning based data analysis for segmentation and synapse 
identification.
I used CATS to analyze key features of nervous tissue connectivity, ranging from whole tissue 
architecture, neuronal in- and output-fields, down to synapse morphology.
Focusing on the hippocampal circuitry, I quantified synaptic transmission properties of mossy 
fiber boutons and analyzed the connectivity pattern of dentate gyrus granule cells with CA3 
pyramidal neurons. This shows that CATS is a viable tool to study hallmarks of neuronal 
connectivity with light microscopy.},
  author       = {Michalska, Julia M},
  isbn         = {978-3-99078-026-8},
  issn         = {2663-337X},
  pages        = {201},
  publisher    = {Institute of Science and Technology Austria},
  title        = {{A versatile toolbox for the comprehensive analysis of nervous tissue organization with light microscopy}},
  doi          = {10.15479/at:ista:12470},
  year         = {2023},
}

@phdthesis{12531,
  abstract     = {All visual experiences of the vertebrates begin with light being converted into electrical signals
by the eye retina. Retinal ganglion cells (RGCs) are the neurons of the innermost layer of the
mammal retina, and they transmit visual information to the rest of the brain.
It has been shown that RGCs vary in their morphology and genetic profiles, moreover they can
be unambiguously grouped into subtypes that share the same morphological and/or molecular
properties. However, in terms of RGCs function, it remains unclear how many distinct types
there are and what response properties their typology relies on. Even given the recent studies
that successfully classified RGCs in a patch of the retina [1] and in scotopic conditions [2], the
question remains whether the found subtypes persist across the entire retina.
In this work, using a novel imaging method, we show that, when sampled from a large portion
of the retina, RGCs can not be clearly divided into functional subtypes. We found that in
photopic conditions, which implies more prominent natural scene statistic differences across
the visual field, response properties can be exhibited by cells differently depending on their
location in the retina, which leads to formation of a gradient of features rather than distinct
classes.
This finding suggests that RGCs follow a global organization across the visual field of the
animal, adapting each RGC subtype to the requirements imposed by the natural scene statistics.},
  author       = {Kirillova, Kseniia},
  issn         = {2791-4585},
  pages        = {46},
  publisher    = {Institute of Science and Technology Austria},
  title        = {{Panoramic functional gradients across the mouse retina}},
  doi          = {10.15479/at:ista:12531},
  year         = {2023},
}

@phdthesis{14323,
  abstract     = {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.},
  author       = {Kuzmicz-Kowalska, Katarzyna},
  issn         = {2663-337X},
  pages        = {151},
  publisher    = {Institute of Science and Technology Austria},
  title        = {{Regulation of neural progenitor survival by Shh and BMP in the developing spinal cord}},
  doi          = {10.15479/at:ista:14323},
  year         = {2023},
}

@article{13136,
  abstract     = {Despite its fundamental importance for development, the question of how organs achieve their correct size and shape is poorly understood. This complex process requires coordination between the generation of cell mass and the morphogenetic mechanisms that sculpt tissues. These processes are regulated by morphogen signalling pathways and mechanical forces. Yet, in many systems, it is unclear how biochemical and mechanical signalling are quantitatively interpreted to determine the behaviours of individual cells and how they contribute to growth and morphogenesis at the tissue scale. In this review, we discuss the development of the vertebrate neural tube and somites as an example of the state of knowledge, as well as the challenges in understanding the mechanisms of tissue size control in vertebrate organogenesis. We highlight how the recent advances in stem cell differentiation and organoid approaches can be harnessed to provide new insights into this question.},
  author       = {Minchington, Thomas and Rus, Stefanie and Kicheva, Anna},
  issn         = {2452-3100},
  journal      = {Current Opinion in Systems Biology},
  publisher    = {Elsevier},
  title        = {{Control of tissue dimensions in the developing neural tube and somites}},
  doi          = {10.1016/j.coisb.2023.100459},
  volume       = {35},
  year         = {2023},
}

@article{12837,
  abstract     = {As developing tissues grow in size and undergo morphogenetic changes, their material properties may be altered. Such changes result from tension dynamics at cell contacts or cellular jamming. Yet, in many cases, the cellular mechanisms controlling the physical state of growing tissues are unclear. We found that at early developmental stages, the epithelium in the developing mouse spinal cord maintains both high junctional tension and high fluidity. This is achieved via a mechanism in which interkinetic nuclear movements generate cell area dynamics that drive extensive cell rearrangements. Over time, the cell proliferation rate declines, effectively solidifying the tissue. Thus, unlike well-studied jamming transitions, the solidification uncovered here resembles a glass transition that depends on the dynamical stresses generated by proliferation and differentiation. Our finding that the fluidity of developing epithelia is linked to interkinetic nuclear movements and the dynamics of growth is likely to be relevant to multiple developing tissues.},
  author       = {Bocanegra, Laura and Singh, Amrita and Hannezo, Edouard B and Zagórski, Marcin P and Kicheva, Anna},
  issn         = {1745-2481},
  journal      = {Nature Physics},
  pages        = {1050--1058},
  publisher    = {Springer Nature},
  title        = {{Cell cycle dynamics control fluidity of the developing mouse neuroepithelium}},
  doi          = {10.1038/s41567-023-01977-w},
  volume       = {19},
  year         = {2023},
}

@phdthesis{13081,
  abstract     = {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.},
  author       = {Bocanegra, Laura},
  issn         = {2663-337X},
  pages        = {93},
  publisher    = {Institute of Science and Technology Austria},
  title        = {{Epithelial dynamics during mouse neural tube development}},
  doi          = {10.15479/at:ista:13081},
  year         = {2023},
}