Integrated Calendar

The talk will describe nonlinear rheology in extreme conditions that change fluid structure and flow mechanisms. Elongational flow of entangled polymers produces near complete molecular alignment but only changes the viscosity by an order of magnitude and does not destroy the confining tube. A transition in the mechanism of shear thinning in lubricants from alignment to thermal activation is shown to be generic and allows simulations to examine whether the viscosity diverges at a finite glass transition temperature.

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.