Neuromuscular Organoids to Study Spinal Cord Development and Disease.

Many aspects of neurodegenerative disease pathology remain unresolved. Why do certain neuronal subpopulations acquire vulnerability to stress or mutations in ubiquitously expressed genes, while others remain resilient? Do these neurons harbor intrinsic marks that make them prone to degeneration? Do these diseases have a neurodevelopmental component? Lacking this fundamental knowledge hampers the discovery of efficacious treatments. While it is well established that human organoids enable the modeling of brain-related diseases, we still lack an organoid model that recapitulates the regionalization complexity and physiology of the spinal cord.

Isogenic patient-derived organoids reveal early neurodevelopmental defects in spinal muscular atrophy initiation.

Whether neurodevelopmental defects underlie postnatal neuronal death in neurodegeneration is an intriguing hypothesis only recently explored. Here, we focus on spinal muscular atrophy (SMA), a neuromuscular disorder caused by reduced survival of motor neuron (SMN) protein levels leading to spinal motor neuron (MN) loss and muscle wasting. Using the first isogenic patient-derived induced pluripotent stem cell (iPSC) model and a spinal cord organoid (SCO) system, we show that SMA SCOs exhibit abnormal morphological development, reduced expression of early neural progenitor markers, and accelerated expression of MN progenitor and MN markers.

Topological Bogoliubov Quasiparticles from Bose-Einstein Condensate in a Flat Band System.

For bosons with flat energy dispersion, condensation can occur in different symmetry sectors. Here, we consider bosons in a kagome lattice with π-flux hopping, which, in the presence of mean-field interactions, exhibit degenerate condensates in the Γ and the K point. We analyze the excitation above both condensates and find strikingly different properties: For the K-point condensate, the Bogoliubov-de Gennes (BdG) Hamiltonian has broken particle-hole symmetry and exhibits a topologically trivial quasiparticle band structure.

Spinal Cord Organoids to Study Motor Neuron Development and Disease.

Motor neuron diseases (MNDs) are a heterogeneous group of disorders that affect the cranial and/or spinal motor neurons (spMNs), spinal sensory neurons and the muscular system. Although they have been investigated for decades, we still lack a comprehensive understanding of the underlying molecular mechanisms; and therefore, efficacious therapies are scarce. Model organisms and relatively simple two-dimensional cell culture systems have been instrumental in our current knowledge of neuromuscular disease pathology; however, in the recent years, human 3D in vitro models have transformed the disease-modeling landscape.

Detecting Majorana Zero Modes via Strong Field Dynamics.

We propose a protocol to detect topological phase transitions of one-dimensional -wave superconductors from their harmonic emission spectra in strong fields. Specifically, we identify spectral features due to radiating edge modes, which characterize the spectrum and the density of states in the topological phase and are absent in the trivial phase. These features allow us to define a measurable signature, obtained from emission measurements, that unambiguously differentiates between the two phases.

Chiral Transport of Hot Carriers in Graphene in the Quantum Hall Regime.

Photocurrent (PC) measurements can reveal the relaxation dynamics of photoexcited hot carriers beyond the linear response of conventional transport experiments, a regime important for carrier multiplication. Here, we study the relaxation of carriers in graphene in the quantum Hall regime by accurately measuring the PC signal and modeling the data using optical Bloch equations. Our results lead to a unified understanding of the relaxation processes in graphene over different magnetic field strength regimes, which is governed by the interplay of Coulomb interactions and interactions with acoustic and optical phonons.

High-harmonic spectroscopy of quantum phase transitions in a high-Tc superconductor.

We report on the nonlinear optical signatures of quantum phase transitions in the high-temperature superconductor YBCO, observed through high harmonic generation. While the linear optical response of the material is largely unchanged when cooling across the phase transitions, the nonlinear optical response sensitively imprints two critical points, one at the critical temperature of the cuprate with the exponential growth of the surface harmonic yield in the superconducting phase and another critical point, which marks the transition from strange metal to pseudogap phase. To reveal the underlying microscopic quantum dynamics, a strong-field quasi-Hubbard model was developed, which describes the measured optical response dependent on the formation of Cooper pairs.

Correction of a Factor VIII genomic inversion with designer-recombinases.

Despite advances in nuclease-based genome editing technologies, correcting human disease-causing genomic inversions remains a challenge. Here, we describe the potential use of a recombinase-based system to correct the 140 kb inversion of the F8 gene frequently found in patients diagnosed with severe Hemophilia A. Employing substrate-linked directed molecular evolution, we develop a coupled heterodimeric recombinase system (RecF8) achieving 30% inversion of the target sequence in human tissue culture cells.

Phonon-Induced Pairing in Quantum Dot Quantum Simulator.

Quantum simulations can provide new insights into the physics of strongly correlated electronic systems. A well-studied system, but still open in many regards, is the Hubbard-Holstein Hamiltonian, where electronic repulsion is in competition with attraction generated by the electron-phonon coupling. In this context, we study the behavior of four quantum dots in a suspended carbon nanotube and coupled to its flexural degrees of freedom.

Fractional Angular Momentum and Anyon Statistics of Impurities in Laughlin Liquids.

The elementary excitations of a fractional quantum Hall liquid are quasiparticles or quasiholes that are neither bosons nor fermions, but are so-called anyons. Here we study impurity particles immersed in a quantum Hall liquid that bind to the quasiholes via repulsive interactions with the liquid. We show that the angular momentum of an impurity is given by the multiple of a fractional "quantum" of angular momentum, and can directly be observed from the impurity density.

Pathogenic Pathways in Early-Onset Autosomal Recessive Parkinson's Disease Discovered Using Isogenic Human Dopaminergic Neurons.

Parkinson's disease (PD) is a complex and highly variable neurodegenerative disease. Familial PD is caused by mutations in several genes with diverse and mostly unknown functions. It is unclear how dysregulation of these genes results in the relatively selective death of nigral dopaminergic neurons (DNs).

Quantum Annealing with Longitudinal Bias Fields.

Quantum annealing aims at solving hard computational problems through adiabatic state preparation. Here, I propose to use inhomogeneous longitudinal magnetic fields to enhance the efficiency of the annealing. Such fields are able to bias the annealing dynamics into the desired solution, and in many cases, suitable field configurations can be found iteratively.

Fractional Quantum Hall Phases of Bosons with Tunable Interactions: From the Laughlin Liquid to a Fractional Wigner Crystal.

Highly tunable platforms for realizing topological phases of matter are emerging from atomic and photonic systems and offer the prospect of designing interactions between particles. The shape of the potential, besides playing an important role in the competition between different fractional quantum Hall phases, can also trigger the transition to symmetry-broken phases, or even to phases where topological and symmetry-breaking order coexist. Here, we explore the phase diagram of an interacting bosonic model in the lowest Landau level at half filling as two-body interactions are tuned.

Blocking p62-dependent SMN degradation ameliorates spinal muscular atrophy disease phenotypes.

Spinal muscular atrophy (SMA), a degenerative motor neuron (MN) disease, caused by loss of functional survival of motor neuron (SMN) protein due to SMN1 gene mutations, is a leading cause of infant mortality. Increasing SMN levels ameliorates the disease phenotype and is unanimously accepted as a therapeutic approach for patients with SMA. The ubiquitin/proteasome system is known to regulate SMN protein levels; however, whether autophagy controls SMN levels remains poorly explored.

Light-Induced Fractional Quantum Hall Phases in Graphene.

We show how to realize two-component fractional quantum Hall phases in monolayer graphene by optically driving the system. A laser is tuned into resonance between two Landau levels, giving rise to an effective tunneling between these two synthetic layers. Remarkably, because of this coupling, the interlayer interaction at nonzero relative angular momentum can become dominant, resembling a hollow-core pseudopotential.

Quantum annealing for the number-partitioning problem using a tunable spin glass of ions.

Exploiting quantum properties to outperform classical ways of information processing is an outstanding goal of modern physics. A promising route is quantum simulation, which aims at implementing relevant and computationally hard problems in controllable quantum systems. Here we demonstrate that in a trapped ion setup, with present day technology, it is possible to realize a spin model of the Mattis-type that exhibits spin glass phases.

Quantum chaos in SU(3) models with trapped ions.

A scheme to generate long-range spin-spin interactions between three-level ions in a chain is presented, providing a feasible experimental route to the rich physics of well-known SU(3) models. In particular, we demonstrate different signatures of quantum chaos which can be controlled and observed in experiments with trapped ions.