לוח שנה משולב

Exocytosis occurs in all living cells and is essential for many cellular processes including metabolism, signaling, and trafficking. During exocytosis, cargo loaded vesicles dock and fuse with the plasma membrane to release their content. To accommodate different cargos and cellular needs exocytosis must occur across scales; From synaptic vesicles that are only ~50nm in diameter, and neuroendocrine vesicles that are in the ~500nm range to giant secretory vesicles filled with viscous cargo, such as in the acinar cells in the exocrine pancreas, that reach up to a few µm in diameter. Yet, how fusion and content release are adapted to remain function across these scales is not well understood. It is well established that during exocytosis of small vesicles, vesicle fusion can proceed through one of two pathways: The first is complete incorporation, when the vesicular membrane fuses to the target membrane and the fusion pore expand irreversibly, incorporating the vesicular membrane into the target membrane. The second is “kiss-and-run”, when the fusion pore flickers, opening briefly and collapsing rapidly into two separate membranes. I am interested in understanding how exocytosis occurs in giant vesicles witch challenge efficient secretion and membrane homeostasis due to their massive size and viscous content. I am using the salivary gland of D. Melanogaster, as a model system for giant vesicles secretion. The vesicles in the gland measure between 5-8 µm, fuse and secrete viscous content into a preformed lumen. To visualize the secretion process, I adapted a method for super-resolution microscopy to live-gland imaging. I observed that fusion pores of giant vesicles expand to a stable opening of up to 3µm and slowly constricts down to hundreds of nm or less during secretion. Because constricting a membrane pore from “infinity” in molecular terms, back to a very narrow ‘stalk’ demands an investment of energy, I hypothesized that this is mediated by a specialized protein machinery. I am currently screening for the components of the machinery using the enormous power of Drosophila genetics by taking a candidate gene approach. My preliminary results identify the BAR domain containing protein, MIM (missing in metastasis) as a key regulator of pore dynamics, leading to new and exciting insights into the molecular mechanism of cellular secretion and membrane homeostasis in live tissues.

Interferons (IFNs) were the first cytokines discovered over half a century ago as agents that interfere with viral infection. IFNs have been established as pleiotropic, multifunctional proteins in the early immune response. They exhibit antiviral and antiproliferative effects, in addition to various immunomodulatory activities. Human type I IFN family consists of 16 members, all acting through the same cell surface receptors, IFNAR1 and IFNAR2. Here, we show that synthetic interferon receptors can activate the Jak/Stat pathway using non-physiological ligands. High affinity GFP and mCherry nanobodies were fused to transmembrane and intracellular domains of the receptors in attempt to perform in-vivo and in-vitro biophysical assays. This will help in better understanding the structure - function relationship of the receptors and their associated ligands.

The vomeronasal system is a chemosensory system devoted to processing cues from other organisms. In my talk I will describe a set of studies from our lab that aim to reveal how chemosensory information is represented by neuronal activity in the AOB (accessory olfactory bulb), the first brain region receiving vomeronasal inputs. After reviewing some of our published work on basic aspects of stimulus representations, I will describe unpublished work in which we explore neuronal correlates of behavioral imprinting, reproductive-state dependent processing, and changes in the genetic background of the subject organism. Taken together, these studies point at a high degree of stability of stimulus representations at the level of the AOB. Finally, I will show that despite its presumed role in processing innately relevant cues, the vomeronasal system has considerable capacity to form novel stimulus response associations, providing further support for the idea that responses to innately relevant cues can be dramatically altered as a result of experience.

Cell migration and cell mechanics play a crucial role in a number of key biological processes, such as embryo development or cancer metastasis. Understanding the way cells control their own material properties and mechanically interact with their environment is key. At a more fundamental level, there is need better measure, describe and monitor cell and tissue mechanics before we can formulate testable hypotheses. In this talk, I will report experimental studies on the mechanical response of two different multicellular structures: epithelial monolayers and early embryonic tissues. In both cases, the material exhibits a strong time-dependent response over a broad distribution of time-scales. The combination of mechanical characterisation with biological perturbations offers new insight into the mechanisms exploited by cells and tissue to control their mechanical properties.
This insight is however limited by the lack of consistency in experimental protocols and modelling strategies used in the field. We recently developed a systematic approach to capture material properties from mechanical behaviours and made progress assessing the model’s generality over a broad range of biological systems

Exploring multisensory interactions requires a definition for a single sense. As such, the first part of the talk with focus on the question of "how many senses are there?". Within this discussion, there are interactions between senses that form the mainstay of the multisensory literature. Two factors—space and time—form a foundation for considering when stimuli will be integrated. One series of experiments will focus on the resolution of conflicts between our internal reference frame and the external reference frame by examining the interaction of touch and proprioception in the crossed-hands TOJ deficit. The final section of the talk will explore the developmental trajectory for interactions between different primary modalities: vision, touch, and audition. Overall, the goal of the talk is to introduce the concept of multisensory integration and give the audience a sample of research questions ongoing in our lab.


Light refreshments before the seminar