לוח שנה משולב

Our work has highlighted the function of Rab GTPases as key components for the biogenesis, transport and function of cellular membrane organelles. The specificity and directionality of membrane fusion is mediated by Rab GTPases and tethering effectors, such as EEA1, which is recruited on the early endosome membrane and binds to Rab5. EEA1 is a long dimeric coiled-coil tether molecule. Upon binding to its N-terminus, Rab5 induces conformational changes on EEA1, from extended to a more flexible “collapsed” state, giving rise to an effective force. Our recent studies suggest that Rab5 and EEA1 effectively constitute a two-component molecular motor, cyclically converting the free energy of GTP binding and hydrolysis into mechanical work. We are now combining biochemical, quantitative image analysis and 3D primary cell culture approaches to explore the role of Rab GTPases and endocytic mechanisms in liver tissue organization and regeneration. Hepatocytes are polarized cells at the interface of both sinusoidal endothelial and bile canaliculi (BC) networks that transport blood and bile between portal and central vein, respectively. In contrast to simple epithelia, where the cells have a single apical surface facing the lumen of organs, hepatocytes exhibit a multipolar (biaxial) organization, i.e. have multiple apical and basal domains. We studied the mechanism of hepatocyte polarization by using a hepatoblasts culture system. We discovered that, during lumen formation, hepatoblasts create apical protrusions along the tight junction belt that connects them, suggesting that these are responsible for the anisotropic growth of apical lumina. These protrusions form a pattern reminiscent of the bulkheads of boats ships and planes. Similarly, the apical bulkheads of hepatocytes are structural elements which can provide such anisotropy and mechanical stability to the elongating cylindrical lumen under inner pressure.

Investigating conscious intentions associated with spontaneous, voluntary action is challenging. Typical paradigms inherently lack the stimulus-response structure that is common in neuroscientific tasks (Haggard, 2019). Moreover, studying the onset of intentions has proven notoriously difficult, conceptually and empirically. Measuring the onset of intentions with a clock was shown to be inconsistent, biased, and unreliable (Maoz et al., 2015). Furthermore, probe methods estimated intention onset much earlier than clock-based methods (Matsuhashi & Hallett, 2008), complicating the reconciliation of these results. Some have even questioned the existence of intentions as discrete, causal neural states (Schurger & Utihol, 2015).

It is fairly well known that Shor's algorithm for Factoring and Discrete Logarithm poses a challenge for cryptography in a quantum world. However, the implications of the viability of the quantum model on cryptography are much more profound, on a number of aspects. Naturally, it is harder to protect against quantum attackers than against classical ones, especially if the honest users remain classical. On the other hand, quantum computation and communication also present new tools that may assist in performing some cryptographic tasks. Further, the quantum model brings about new potential capabilities and cryptographic tasks that need to be explored, most basically the ability to prove that a potentially untrusted device indeed performs a quantum task.

In the talk I will explain how computer scientists, and in particular cryptographers, perceive the quantum computing model. I will discuss some of the fundamental questions that come up when the quantum model is incorporated into cryptography, such as the security of "lattice assumptions" against quantum attacks, the rewinding problem in cryptographic reductions, and the notion of semi-quantum cryptography which addresses questions in classical-quantum interaction.
No background in computer science or cryptography will be assumed.

Hybrid seminar
Location: Physics library (Benoziyo Physics building, second floor)
Zoom link: https://weizmann.zoom.us/j/99771276053?pwd=K3N6NEpPemh6aDZ2dEpJUU5HRXo4UT09

Positive-strand RNA viruses including corona, zika and dengue are a major threat to public health. A critical step in the life cycle of all positive-strand RNA viruses is the replication of their genome on cellular membranes called replication compartments. However, the mechanisms underlying the formation of the replication compartments are not well understood. Enteroviruses are positive-strand RNA viruses that cause diverse medical complications in humans including myocarditis, meningitis and paralysis. Combining biochemistry, molecular and cellular biology approaches, we discovered that enteroviruses hijack lipid storage organelles called lipid droplets and use the lipids stored within them to generate their replication compartments. I will describe the sophisticated viral mechanisms involved in the hijack of lipid droplets and the channeling of their content to promote virus replication. Our studies illuminate the mechanisms by which positive-strand RNA viruses rewire host organelles and lipid metabolism and provide a snapshot into the complex replication program of these viruses.

Abstract: Research in quantum computing has offered many new physical insights and a potential to exponentially increase the computational power that can be harnessed to solve important problems in science and technology. The largest fundamental barrier to building a scalable quantum computer is errors caused by decoherence. Topological quantum computing overcomes this barrier by exploiting topological materials which, by their nature, limit errors. In this colloquium, I will discuss how to engineer topological superconductors supporting Majorana zero-energy modes at the interface of a conventional superconductor and a semiconductor with spin-orbit interaction. I will present recent results by the Microsoft Quantum team consistent with the emergence of topological superconductivity in proximitized semiconductor nanowires. Finally, I will present a proposal for scalable quantum computing involving topological qubits which comprise of superconducting islands in a Coulomb blockade regime hosting aggregates of four or more Majorana zero modes.

Dahlia Kushinsky- Daily normalization of E/I-ratio by light-driven transcription maintains visual processing

Abstract: Consistent and reliable encoding of sensory information is essential for an animal’s survival. However, sensory input in an animal’s environment is constantly changing, likely resulting in changes in the brain at the level of molecules, synapses, and cellular circuitry. It is therefore unclear which elements of the system are stable or dynamic, and what mechanisms allow for overall stability of the brain throughout an animal’s life. To address this question, we focused on the visual cortex of adult mice and took advantage of the daily sensory transitions from the dark of night to daylight and back to darkness during a single day. By using RNA-seq, patch clamp slice electrophysiology, and in vivo longitudinal calcium imaging in awake mice, we monitor the light driven changes in molecules, synapses, and cells across a single day. At each of these levels (molecular, synaptic, and cellular), we find rapid sensory-driven increases shortly after transition from darkness to light which is then normalized later in the day. Based on these findings, we suggest that sensory-driven genetic changes maintain functional stability of neural circuits by regulating E/I ratio in excitatory neurons every day.

Michael Sokoletsy-
Isolated correlates of perception in the posterior cortex

Abstract: To uncover the neural mechanisms of stimulus perception, experimenters commonly use tasks in which subjects are repeatedly presented with a weak stimulus and instructed to report, via movement, if they perceived the stimulus. The difference in neural activity between reported stimulus (hit) and unreported stimulus (miss) trials is then seen as potentially perception-related. However, recent studies found that activity related to the report spreads throughout the brain, calling into question to what extent such tasks may be conflating activity that is perception-related with activity that is report-related. To isolate perception-related activity, we developed a paradigm in which the same mice were trained to report either the presence or absence of a whisker stimulus. We found that isolated perception-related activity appeared within a posterio-parietal network of cortical regions contralateral to the stimulus, was on average an order of magnitude lower than the hit versus miss difference, and began just after the low-level stimulus response. In addition, we performed controls to check that it is specifically associated with performance and is not the result of differences in time or uninstructed movements across the tasks. In summary, we revealed for the first time in mice the cortical areas that are associated specifically with the perception of a sensory stimulus and independently of the report.