How the organs of a developing organism achieve their correct size and shape is a fundamental unresolved question in biology. Mammalian embryos possess a remarkable ability to regulate (restore) the correct size of their tissues and organs upon perturbations during early development, yet how this is achieved is unknown. Addressing this question has so far been challenging because it requires a multiscale approach that integrates precise measurements with theoretical frameworks. We are now in an excellent position to unravel the mechanisms by which the mouse spinal cord regulates its size and shape during development by building on our experience with quantitative studies in this system. We previously obtained quantitative spatiotemporal data of growth, pattern and morphogen signalling dynamics in the spinal cord. We showed that there is a critical period during which morphogen signaling is interpreted to specify cell fates, uncovered a mechanism that allows precise pattern formation, and identified a link between the growth rate and tissue anisotropy. Our expertise now enables us to address the following new questions: 1) how is size regulation in the spinal cord achieved at the tissue and cellular level; 2) what is the molecular mechanism of size regulation, in particular the role of morphogen signaling; 3) how is the regulation of spinal cord size linked to the regulation of its shape. To address these questions, we will combine precisely controlled ex vivo assays in organoids and whole embryo culture, and in vivo advanced mouse genetics and mosaic analysis. We will obtain highly resolved dynamic data and interpret it in the context of rigorous theoretical frameworks. The project will advance our understanding of the fundamental mechanisms of tissue size control and the constraints they impose in regeneration and disease. Our results will have implications for in vitro tissue engineering and research on multi-organ coordination and robustness during development.

Fractional quantum Hall (FQH) states are paradigmatic examples of strongly correlated topological quantum matter, combining geometric order and strong interparticle interactions. Yet, limited microscopic control in solid-state platforms often restricts observations to global current or spectroscopy probes. Engineered quantum systems, such as ultracold atoms in optical lattices, offer a complementary route for exploring topological order leveraging precise control over Hamiltonian parameters and access to local observables through quantum gas microscopy. The primary goal of this project is to prepare and probe quantum-engineered fermionic FQH states for the first time in a next-generation quantum gas microscope. First, we will implement direct laser cooling of fermionic Li-6 atoms to efficiently prepare individual atoms in the ground state of optical tweezers, and holographically project lattice potentials to assemble Fermi-Hubbard systems atom by atom. To explore FQH physics, we will implement small fermionic Harper-Hofstadter systems via Floquet engineering. Leveraging our system’s excellent coherence, we will extend observations beyond two particles and perform first observations fractionally charged quasi-hole excitations pinned by local repulsive potentials. To access a broader class of fermionic FQH states, we will build upon recent advances in multi-orbital lattices and engineer p-wave interactions between pairs of spinless fermions. This approach will facilitate first microscopic studies of exotic Pfaffian states. Our results will significantly impact research in quantum simulation and topological physics. Technically, we will advance programmable optical lattices, enabling sub-second cycle times and unprecedented levels of control in quantum gas microscopes. Implementing p-wave interactions will facilitate the exploration of Pfaffian states and non-Abelian excitations, which are building blocks for fault-tolerant topological quantum computing.

Cell motility is driven by a complex network of force-generating biological machinery. The key component in this machinery is the dynamic network of filamentous actin (F-actin) and actin binding proteins (ABPs) which maintain and regulate the network. However, structural information for many ABP-actin complexes, as well as their in situ spatial distribution remain elusive. This is because ABPs cannot be easily studied in isolation, often exhibiting structural stability only when embedded in a complex filamentous network found within cells. This has hindered a complete understanding of actin network regulation in cell migration. Addressing this important question requires understanding exactly how ABPs select F-actin, and conversely how F-actin geometry recruits specific ABPs. Cryo-electron tomography (cryo-ET) can reveal both cellular ultrastructure and molecular details, but often is lower resolution than a single particle cryo-EM approach. Thus, innovative methods remain key to drive advancement in understanding in situ structures. In this fellowship I will combine my expertise of single particle cryo-electron microscopy with expertise of cryo-ET in the Schur lab to develop a novel hybrid single particle cryo-ET approach in order to reveal high-resolution structures and contextual information of ABPs bound to F-actin directly within cellular protrusions. ISTA is the ideal research institute due to abundant access to high-end electron microscopes necessary for methods development. The outcome of this action are tools for high resolution in situ structure determination and a better understanding of cell migration, a process deeply rooted in malignant metastasis. Results will be disseminated through key research conferences and high-impact open-access publications. Communication activities will be achieved through 3D rendered visual scientific illustrations targeting social media platforms and institute-organized public outreach events.

TROPIC will design new experiments to uncover the topological properties of quantum materials that will revolutionize quantum computing. Conventional approaches that rely on local interactions between qubits suffer from seemingly insurmountable problems, such as controlling quantum decoherence while still achieving a useful number of qubits. Alternative approaches based on nonlocal topological excitations, such as Majorana fermions, could provide a solution but clear evidence for their existence is missing. TROPIC aims to identify topological signatures of quantum spin liquids and superconductors by revolutionizing a technique—resonant torsion magnetometry—that was recently developed by the PI. Our approach is unique in its extreme sensitivity to materials properties that are notoriously concealed. This proposal consists of three aims that focus on systems with promising hints of topology: the quantum spin liquid RuCl3 and the spin triplet superconductor UTe2. Each aim requires significant advances that will allow us to access the magnetotropic coefficient—the thermodynamic coefficient associated with magnetic anisotropy—in new classes of materials for the first time (aim 2) while obtaining new information (aim 3). The aims are summarized as: 1. Refining resonant torsion to identify topological order associated with Majorana fermions in RuCl3. 2. Extending resonant torsion to high magnetic fields to investigate unconventional superconductivity in UTe2. 3. Developing resonant torsion to higher frequencies to search for slow topological excitations. Recent media articles by quantum computing pioneers have warned that the hype is surpassing the performance. A material revolution is needed to realize the promise of quantum computing. We will develop a new experimental probes that will be applicable to broad classes of topological materials, including small and fragile 2D systems and heterostructures where thermodynamic measurements are needed.

This proposal will focus on the hippocampal mossy fiber (MF) synapse, formed between the axons of dentate gyrus granule cells and CA3 pyramidal neurons. The hippocampus plays an important role in learning and memory formation and MF synapses are involved in processing, storage and recall of spatial information. The MF tract connects the entorhinal cortex to CA3 pyramidal neurons. MF presynaptic terminals are large in size, forming giant synapses on proximal dendrites of CA3 pyramidal neurons. Based on this structure, the MF synapse is proposed to have a key role in hippocampal function as a “detonator synapse” that reliably discharges the postsynaptic target neurons. Additionally, it is thought to be involved in storage of information in the CA3 region network by triggering synaptic plasticity between these pyramidal neurons. Despite its important role in hippocampal function and plasticity, there is still very limited information about this key synapse. This proposal will investigate the nanoscale location and distribution of presynaptic voltage-gated calcium channels (VGCCs) at the hippocampal mossy fiber synapse and how it influences coupling at this presynaptic terminal. The opening of VGCCs at presynaptic terminals leads to calcium entry and a subsequent rise in concentration in the vicinity of the channels. The spatial volume occupied by this increased calcium concentration is referred to as calcium domains. The coupling distance between these domains and calcium sensors at the release machinery of docked synaptic vesicles is critical as it determines speed and precision of fusion of vesicles and, thus, release of neurotransmitters. Results from these observations would form the basis for a quantitative understanding of mechanisms underlying time-course of transmission and presynaptic plasticity at this synapse and thus, how it relates to their particular network function in hippocampus.