לוח שנה משולב

Shigella flexneri is a bacterial entero-invasive pathogen transmitted through the fecal/oral route causing bacillary dysentery in humans. Shigella pathogenicity solely relies on a needle-like molecular syringe, the Type 3 Secretion System (T3SS) that injects more than 20 bacterial effectors to infect colonic epithelial cells. The T3SS is composed of a basal body that controls and initiates effector secretion and a needle complex that acts as a conduit for effector delivery. The needle is capped by a tip complex that regulates whether the needle is closed or whether it secretes. Sensing of host cells by the needle tip complex induces a conformational switch that remodels the tip and activates the T3SS to form a channel, the translocon pore at the distal end. Effectors are then actively secreted, promoting cell invasion and endocytosis of the bacteria in a tight vacuole derived from the host plasma membrane called Bacteria Containing Vacuole (BCV). Quickly after entry, the pathogen ruptures its BCV and establish a replicative cytosolic niche. Vacuolar rupture consists of a first step of BCV breakage followed by BCV remnants unpeeling. The team has identified bacterial effectors promoting efficient vacuole unpeeling but the direct role of the T3SS in membrane destabilization is not clear. I have overcome these limitations by investigating the T3SS/vacuole interactions at the onset of vacuolar rupture using a novel cryo-Correlative Light Electron Microscopy (CLEM) workflow applied in situ, during the host-pathogen crosstalk. Cryo-CLEM allows the combination of high-resolution information in 3D, accessed via cryo-Electron Tomography (cryo-ET) to functional information brought by light microscopy. This pipeline benefits from in-house custom-built genetically encoded reporter cell lines which are used to identify precise steps of the infection at high spatiotemporal resolution.
Using this workflow, I collected cryo-ET data on Shigella-infected epithelial cells. I have been able to visualize the Shigella T3SS at molecular resolution providing unprecedented information. Particularly, I am looking at (i) the contact sites between T3SS and BCV membrane; (ii) T3SS morphologies depending on its activation state. Together this work will allow to precisely describe the interplay between host and bacteria processes.

Nanoparticles and nanostructures are at the heart of next generation technological solutions in sustainable energy, effective new pharmaceuticals and environmental remediation. A key to making progress is to be able to understand the nanoparticle structure, the arrangements of atoms in the nanoparticles and nanoscale structures. Also critical is understanding the distribution of the nanoparticles and how they change in time as devices run and reactions take place. We use advanced x-ray, neutron and electron scattering methods to get at this problem. I will talk about these methods and show some recent success-stories in the fields of sustainable energy, pharmaceuticals and cultural heritage preservation. However, I will also discuss the fundamental limitations on our ability to extract information from the data and how we are now turning to machine learnging and articifical intelligence techniques to give more insights.

Understanding quantum channels and the strange behavior of their capacities is a key driver of quantum information theory. Despite having rigorous coding theorems, quantum capacities are poorly understood due to super-additivity effects. We will talk about a remarkably simple, low-dimensional, single-parameter family of quantum channels with exotic quantum information-theoretic features. As the simplest example from this family, we focus on a qutrit-to-qutrit channel that is intuitively obtained by hybridizing together a simple degradable channel and a completely useless qubit channel. Such hybridizing makes this channel's capacities behave in a variety of interesting ways. For instance, the private and classical capacity of this channel coincide and can be explicitly calculated, even though the channel does not belong to any class for which the underlying information quantities are known to be additive. Moreover, the quantum capacity of the channel can be computed explicitly, given a clear and compelling conjecture is true. This "spin alignment conjecture," which may be of independent interest, is proved in certain special cases and additional numerical evidence for its validity is provided. We further show that this qutrit channel demonstrates superadditivity when transmitting quantum information jointly with a variety of assisting channels, in a manner unknown before. A higher-dimensional variant of this qutrit channel displays super-additivity of quantum capacity together with an erasure channel. Subject to the spin-alignment conjecture, our results on super-additivity of quantum capacity extend to lower-dimensional channels as well as larger parameter ranges. In particular, super-additivity occurs between two weakly additive channels each with large capacity on their own, in stark contrast to previous results. Remarkably, a single, novel transmission strategy achieves super-additivity in all examples. Our results show that super-additivity is much more prevalent than previously thought. It can occur across a wide variety of channels, even when both participating channels have large quantum capacity.

This is joint work with Debbie Leung, Vikesh Siddhu, Graeme Smith, and John Smolin, and based on the papers https://arxiv.org/abs/2202.08380 and https://arxiv.org/abs/2202.08377.

Abstract: Around the world, several groups are working to detect very
low frequency gravitational waves using "pulsar timing arrays". The
gravitational waves are generated by orbiting pairs of extremely
massive black holes at cosmological distances from Earth. The
"detector" operates at a Galactic-scale, exploiting radio pulsars
(very stable rapidly-spinning neutron stars) as high precision clocks.
I'll explain how these detectors operate -- the gravitational waves
leave detectable imprints on the radio pulses -- and review the
current state of the field and its prospects. I'll also describe some
recent work (arXiv:2205.05637, arXiv:2208.07230) on the "Hellings and
Downs correlation". This pattern of pulsar timing correlations is the
"smoking gun" that should reveal the presence of gravitational waves.

The role of neuronal activity in the development of neurons and circuits remains controversial. Historically, activity has been seen to be critical for the sculpting of connectivity patterns after the period of synapse formation, often pruning unused synapses and helping to maintain or grow active ones. We now have evidence that a specific type of activity, spontaneous transmitter release, in the past often regarded as simply 'noise', plays a role in synapse formation and the development of dendritic morphology at early stages in the developmental period. Using both in vitro and in vivo approaches in mice to manipulate spontaneous transmitter release and the postsynaptic receptors that detect it, we show that these effects are connection specific in the developing hippocampal circuit. Many of the key synaptic proteins involved are known to be mutated in severe neurodevelopmental disorders, indicating how important these early roles may be in healthy brain development.

I will discuss the synthesis and properties of a range of aromatic-, anti-aromatic- and helical aromatic molecules.1 The talk will feature molecules with 'weird' magnetic properties, helical chirality and abnormal reactivity due to close proximity. I will discuss some of the unusual properties (and some of the very trivial and unsurprising properties) of these large well-defined conjugated molecules. I will describe the journey from fundamental studies of the acid-mediated oligomerization of simple 1,4-benzoquinones to the controlled synthesis of heterocyclic [8] circulenes (featuring an antiaromatic planar cyclooctatetraene) and even a larger planar [9] helicene. In the simplest picture two units of benzoquinone gives a dihydroxy-dibenzofuran + water, thus forming a new furan ring. This sets up a 1+1=3 ‘logic’ for elongation of the -system. The synthetic methodology has allowed us to prepare a range of fully conjugated helicenes, including the longest known optically resolved chiral [13] helicenes. The helicenes and circulenes have been explored in a range of properties including as the blue fluorescent component in OLEDs, as G-quadruplex binding ligands and in fundamental studies of antiaromaticity and chirality.