לוח שנה משולב

Medicine is taking its first steps toward patient-specific cancer care. Nanoparticles have many potential benefits for treating cancer, including the ability to transport complex molecular cargoes, including siRNA and protein, as well as targeting specific cell populations.
The talk will explain the fundamentals of nanotechnology, from ‘barcoded nanoparticles’ that target sites of cancer where they perform a programmed therapeutic task. Specifically, liposomes diagnose the tumor and metastasis for their sensitivity to different medications, providing patient-specific drug activity information that can be used to improve the medication choice.
The talk will also describe how liposomes can be used for degrading the pancreatic stroma to allow subsequent drug penetration into pancreatic adenocarcinoma and how nanoparticle’ biodistribution and anti-cancer efficacy are impacted by the patient’s sex and, more specifically, the menstrual cycle.
The evolution of drug delivery systems into synthetic cells, programmed nanoparticles that have an autonomous capacity to synthesize diagnostic and therapeutic proteins inside the body, and their promise for treating cancer and immunotherapy, will be discussed.


















References:
1) Theranostic barcoded nanoparticles for personalized cancer medicine, Yaari et al. Nature Communications, 2016, 7, 13325
2) Collagenase nanoparticles enhance the penetration of drugs into pancreatic tumors, Zinger et al., ACS Nano, 13 (10), 11008-11021, 2019
3) Targeting neurons in the tumor microenvironment with bupivacaine nanoparticles reduces breast cancer progression and metastases, Science Advances, Kaduri et al., 7 (41), eabj5435, 2021
4) Nanoparticles accumulate in the female reproductive system during ovulation affecting cancer treatment and fertility, Poley et al., ACS nano, 2022

To understand the functional properties of biomolecules, such a small metabolites, protein or nucleic acids, we ought to study them with high resolution in their native context. NMR spectroscopy allows the direct observation of NMR-active nuclei in complex, undefined environments and can thus be employed to investigate isotopically enriched molecules inside live cells. This methodology is known as In-cell NMR and has been used to evaluate the structural properties of proteins, nucleic acids and other biomolecules in physiological environments and to resolve their functional characteristics in a cellular context. These methods have been applied to bacteria, yeasts or cultured mammalian cells. However these cells are clonally grown at high densities in artificial media, lacking the complex tissue context present in higher organisms and its associated biological activities. We funnel our efforts to extend In-cell NMR applications to in vivo conditions using zebrafish embryos and the nematode C. elegans as model organisms. We deliver 15N-isotopically enriched biomolecules, such as small compounds and proteins into fish embryos to delineate their conformational properties and enzymatic conversions. We also enrich live C. elegans with 13C atoms to directly interrogate about their metabolic compositions and enzymatic activities. Combined, these studies provide methodological advancements with regard to high resolution in vivo NMR applications.

Lasing during laser filamentation in the air was discovered about a decade ago. Its physical origins remain puzzling and controversial to this day. Yet, the phenomenon itself appears stubbornly robust and ubiquitous, arising experimentally under many different conditions.
In this talk I will argue that air lasing is a spectacular manifestation of lasing without inversion. In contrast to a frequent belief that lasing without inversion is a delicate, exotic, and fragile phenomenon,
this particular incarnation of it appears as inevitable and as robust as the simple fact that short intense laser pulses inevitably force nitrogen molecules in the air to align, ionize, and continue to rotate after the laser pulse is gone.
I will also point out how one can tailor the initial laser pulse to turn air lasing into lasing with real inversion. The implication is that once you fire your tailored laser pulse sequence into the air, the air might actually fire back at you, within a picosecond or so.

The ultimate purpose of sensory systems is to drive behaviour.  Yet the bulk of textbook knowledge of sensory systems comes from experiments on anaesthetised animals where the motor systems are disengaged.  The broad aim of our research is to investigate the neural basis of sensation in the behaving brain.  In this talk, I will present work that addresses two fundamental issues concerning the function of primary sensory cortex.  First, what role does Sensory Adaptation play under awake, behaving conditions?  Second, to what extent does behaviour modulate sensory processing in freely moving animals?

Visual information is transferred at the ribbon synapse – the first synapse of the visual system – from photoreceptors to bipolar cells and horizontal cells. Whereas multiple bipolar cell types form parallel channels of vertical signal transfer to ganglion cells, the output neurons of the retina, the molecular basis of horizontal function within the retinal circuitry remains enigmatic.
We have combined electrophysiology and calcium imaging with immunocytochemistry as well as single-cell RNA-sequencing and machine-learning approaches to establish a detailed map of voltage- and ligand-gated ion channels expressed by horizontal cells of the vertebrate retina. Our results provide a characteristic molecular signature of ionotropic glutamate receptors responsible for converting photoreceptor signals into postsynaptic membrane potential changes. We suggest that local information processing in horizontal cell dendrites is accompanied by cell-wide signals mediated by activation of voltage-gated calcium and sodium channels, which generate spike-like events. Comparison across different vertebrate species indicates a common theme of ion channel expression with variations based on evolutionary distance.
Correlating the spatio-temporal pattern of horizontal cell activity with the biophysical properties of ion channels and neurotransmitter receptors will provide a better understanding of early signal processing in the vertebrate retina.