Kalender

Cell-cell interactions are governed by the complex and dynamic biophysical landscape of the cell surface. For phagocytic cells like macrophages, the decision to engulf a target is influenced by both the material properties and topography of the interface. We demonstrate that steric crowding of the glycocalyx acts as a physical barrier to antigen accessibility, effectively lowering phagocytic efficiency. We also find that target cortical stiffness serves as a mechanical switch between whole-cell phagocytosis and trogocytosis (cellular "nibbling"). This selective membrane extraction can reshape the molecular identity of both cells through "cross-dressing," a poorly understood process of membrane exchange. By integrating genome-scale CRISPR screens with novel biophysical characterization tools, we are investigating how the interplay of surface crowding and target mechanics defines the appetite of immune cells, offering new physical strategies to regulate immune function and guide other types of cell-cell interactions.

Sleep is an essential state that fulfills higher brain functions as well as basic vital processes. Too little or excessive sleep impairs sleep functions, driving the evolutionary need for precise neural mechanisms that regulate sleep duration. Sleep-active neurons release neurotransmitters and neuropeptides upon depolarization to determine when an organism falls asleep. In C. elegans, the depolarization of the single sleep-active neuron RIS determines sleep via the release of the FLP-11 neuropeptide. Yet, how RIS and FLP-11 control sleep remains unclear. In this talk, I will present how RIS and FLP-11 control sleep through the Gi/o-protein coupled receptor DMSR-1. I will show how, using cell-specific knockdowns, we demonstrate that dmsr-1 induces sleep by acting in cholinergic neurons, while the receptor mediates negative feedback control of RIS that limits sleep duration. Thus, DMSR-1 controls both the initiation and limitation of sleep, effectively coupling sleep induction with a sleep-stop signal. Neuropeptide-GPCR signaling might underlie similar dual mechanisms of sleep control in other species, and self-inhibition of sleep-active neurons might represent a conserved mechanism for limiting the duration of sleep.

TBA

Cell adhesion is essential for shaping tissues during animal development, yet how adhesion is tuned to support different morphogenetic movements remains unclear. We used optogenetics in the Drosophila embryo to address this question by enhancing clustering of E-cadherin, a core component of adherens junctions. Increasing E-cadherin clustering enriches E-cadherin at junctions and reduces its mobility, consistent with enhanced adhesion strength. This approach allows targeted manipulation of cellular adhesive properties in vivo and makes it possible to address questions that were previously difficult to test directly. By analyzing animal development while increasing cell adhesion throughout the epithelial tissue, we found that this causes a strong reduction in cell rearrangements during epithelial morphogenesis and disrupts convergent extension of the embryonic axis. To further understand these effects, we adapted a vertex model to include adhesion-dependent friction between cells. The model predicts that stronger adhesion increases resistance to neighbor exchange and thereby limits tissue remodeling. To test this idea, we analyzed different morphogenetic movements in the fly and their dependence on cell adhesion. We found that enhanced E-cadherin clustering strongly slows morphogenetic processes that depend on both cell shape change and cell rearrangement, while movements that rely primarily on apical constriction can still proceed. Together, these findings suggest that E-cadherin clustering is an important regulator of tissue mechanics and that tuning adhesion is critical for morphogenetic events that require dynamic cell-cell rearrangements

TBA