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Left to right - Prof. Avigdor Eldar, Polina Guler

Research

Mar 17th, 2024
Do Viruses Have Consciousness?

Bacteria-Targeting Viruses Adapt, Improving their Decision-Making

  • Life Sciences

Researchers from the Shmunis School of Biomedicine and Cancer Research at Tel Aviv University have deciphered a novel complex decision-making process that helps viruses choose to turn nasty or stay friendly to their bacterial host. In a new paper, they describe how viruses co-opt a bacterial immune system, intended to combat viruses like themselves, in this decision-making process. The study was led by Polina Guler, a PhD student in Prof. Avigdor Eldar's lab, in addition to other lab members, at the Shmunis School of Biomedicine and Cancer Research, George S. Wise Faculty of Life Sciences. The paper was published in Nature Microbiology.

 

All-You-Can-Eat Bacteriophage

 

Bacteriophages, also known as phages, are types of viruses that infect bacteria and use the infected bacteria to replicate and spread. Even though the word 'bacteriophage,' meaning 'bacteria devouring' in ancient Greek, suggests destruction, many phages can adopt a "sleeping" mode, in which the virus incorporates itself into the bacterial genome. In fact, in this mode of action, the virus can even have a symbiotic relationship with the bacteria, and its genes can help its host prosper.

 

 

In general, Eldar explains that phages usually prefer to stay in the “sleeping”, dormant mode, in which the bacteria "cares" for their needs and helps them safely replicate. Previous research published by the Eldar lab has shown that the phages' decision-making uses two kinds of information to decide whether to stay dormant or turn violent: the "health status" of their host and signals from outside indicating the presence of other phages around.

 

 

"A phage can't infect a cell already occupied by another phage. If the phage identifies that its host is compromised but also receives signals indicating the presence of other phages in the area, it opts to remain with its current host, hoping for recovery. If there is no outside signal, the phage 'understands' that there might be room for it in another host nearby and it’ll turn violent, replicate quickly, kill the host, and move on to the next target", Eldar explains.

 

Death by Phage

 

The new study deciphers the mechanism that enables the virus to make these decisions. "We discovered that in this process the phage actually uses a system that the bacteria developed to kill phages", says Guler. If it does not sense a signal from other phages—indicating that it has a good chance of finding new hosts—the phage activates a mechanism that disables the defense system. "The phage switches to its violent mode, and with the defense system neutralized, it is able to replicate and kill its host", describes Guler. "If the phage senses high concentrations of the signal, instead of disabling the defense system, it utilizes its defense activity in order to turn on its dormant mode".

 

 

"The research revealed a new level of sophistication in this arms race between bacteria and viruses," adds Eldar. Most bacterial defense systems against phages were studied in the context of viruses that are always violent. Far less is known about the mechanisms of attacks and interaction with viruses that have a dormant mode. "The bacteria also have an interest in keeping the virus in the dormant mode, first and foremost to prevent their own death, and also because the genes of the dormant phage might even contribute to bacterial functions," says Eldar.

 

 

“This finding is important for several reasons. One reason is that some bacteria, such as those causing the cholera disease in humans, become more violent if they carry dormant phages inside them - the main toxins that harm us are actually encoded by the phage genome," explains Eldar. “Another reason is that phages can potentially serve as replacements to antibiotics against pathogenic bacteria. Finally, phage research may lead to better understanding of viruses in general and many human-infecting viruses can also alternate between dormant and violent modes”.

Left to right: Prof. Yair Shokef, Dr. Izhar Neder, Chaviva Sirote-Katz

Research

Mar 17th, 2024
Unlocking Quantum Mysteries with Pendula

 

Pendulum Experiment Sheds Light on Quantum Mysteries in Topological Materials, Revealing Insights Unreachable by Traditional Methods

  • Life Sciences

A recent study conducted at Tel Aviv University has devised a large mechanical system that operates under dynamical rules akin to those found in quantum systems. The dynamics of quantum systems, composed of microscopic particles like atoms or electrons, are notoriously difficult, if not impossible, to observe directly. However, this new system allows researchers to visualize phenomena occurring in specialized “topological” materials through the movement of a system of coupled pendula.

 

The research is a collaboration between Dr. Izhar Neder of the Soreq Nuclear Research Center, Chaviva Sirote-Katz of the Department of Biomedical Engineering, Dr. Meital Geva and Prof. Yair Shokef of the School of Mechanical Engineering, and Prof. Yoav Lahini and Prof. Roni Ilan of the School of Physics and Astronomy at Tel Aviv University and was recently published in the Proceedings of the National Academy of Sciences of the USA (PNAS).

 

 

 

Exploring Quantum Wave Phenomena

 

Quantum mechanics governs the microscopic world of electrons, atoms and molecules. An electron, which is a particle that moves in an atom or in a solid, may have properties that give rise to wave-like phenomena. For instance, it may demonstrate a probability of dispersing in space similar to waves spreading out in a pool after a stone is thrown in, or the capability to exist simultaneously in more than one place.

 

 

Such wave-like properties lead to a unique phenomenon that appears in some solid isolators, where even though there is no electric current through them, and the electrons do not move due to an external electric voltage, the internal arrangement of the material shows up in a state referred to as “topological”. This means that the wave of electrons possesses a quantity that can “close on itself” in different ways, somewhat like the difference between a cylinder and a Möbius strip. This “topological” state of the electrons, for which the 2016 Nobel Prize in Physics was awarded, is considered a new state of matter and attracts much current research.

 

Chaviva Sirote-Katz

 

Despite the theoretical interest, there is a limitation in measuring these phenomena in quantum systems. Due to the nature of quantum mechanics, one cannot directly measure the electron’s wave function and its dynamical evolution. Instead, researchers indirectly measure the wave-like and topological properties of electrons in materials, for instance by measuring the electrical conductivity at the edges of solids.

 

 

In the current study, the researchers considered the possibility of constructing a sufficiently large mechanical system that would adhere to dynamical rules akin to those found in quantum systems, and in which they could directly measure everything. To this end, they built an array of 50 pendula, with string lengths that slightly varied from one pendulum to the other. The strings of each neighboring pair of pendula were connected at a controlled height, such that each one’s motion would affect its neighbors’ motion.

 

 

Quantum Pendulum Insights

 

On one hand, the system obeyed Newton’s laws of motion, which govern the physics of our everyday lives, but the precise lengths of the pendula and the connections between them created a magical phenomenon: Newton’s laws caused the wave of the pendulum’s motion to approximately obey Schrödinger’s equation – the fundamental equation of quantum mechanics, which governs the motion of electrons in atoms and in solids. Therefore, the motion of the pendula, which is visible in the macroscopic world, reproduced the behaviors of electrons in periodic systems such as crystals.

 

 

The researchers pushed a few pendula and then released them. This generated a wave that propagated freely along the chain of pendula, and the researchers could directly measure the evolution of this wave – an impossible mission for the motion of electrons. This enabled the direct measurement of three phenomena. The first phenomenon, known as Bloch oscillations, occurs when electrons within a crystal are influenced by an electric voltage, pulling them in a specific direction. In contrast to what one would expect, the electrons do not simply move along the direction of the field, but they oscillate back and forth due to the periodic structure of the crystal. This phenomenon is predicted to appear in ultra-clean solids, which are very hard to find in nature. In the pendula system, the wave periodically moved back and forth, exactly according to Bloch’s prediction.

 

 

The second phenomenon that was directly measured in the pendula system is called Zener tunneling. Tunneling is a unique quantum phenomenon, which allows particles to pass through barriers, in contrast to classical intuition. For Zener tunneling, this appears as the splitting of a wave, the two parts of which then move in opposite directions. One part of the wave returns as in Bloch oscillations, while the other part “tunnels” through a forbidden state and proceeds in its propagation. This splitting, and specifically its connection to the motion of the wave in either direction, is a clear characteristic of the Schrödinger equation.

 

 

In fact, such a phenomenon is what disturbed Schrödinger, and is the main reason for the suggestion of his famous paradox; according to Schrödinger’s equation, the wave of an entire cat can split between a live-cat state and a dead-cat state. The researchers analyzed the pendula motion and extracted the parameters of the dynamics, for instance, the ratio between the amplitudes of the two parts of the split wave, which is equivalent to the quantum Zener tunneling probability. The experimental results showed fantastic agreement with the predictions of Schrödinger’s equation.

 

 

The pendula system is governed by classical physics. Therefore, it cannot mimic the full richness of quantum systems. For instance, in quantum systems, the measurement can influence the system’s behavior (and cause Schrödinger’s cat to eventually be dead or alive when it is viewed). In the classical system of macroscopic pendulum, there is no counterpart to this phenomenon. However, even with these limitations, the pendula array allows the observation of interesting and non-trivial properties of quantum systems, which may not be directly measured in the latter.

 

 

The third phenomenon that was directly observed in the pendula experiment was the wave evolution in a topological medium. Here, the researchers found a way to directly measure the topological characteristic from the wave dynamics in the system – a task that is almost impossible in quantum materials. To this end, the pendula array was tuned twice, so that they would mimic Schrödinger’s equation of the electrons, once in a topological state and once in a trivial (i.e. standard) state. By comparing small differences in the pendulum motion between the two experiments, the researchers could classify the two states. The classification required a very delicate measurement of a difference between the two experiments of exactly half a period of oscillation of a single pendulum after 400 full oscillations that lasted 12 minutes. This small difference was found to be consistent with the theoretical prediction.

 

 

The experiment opens the door to realizing further situations that are even more interesting and complex, like the effects of noise and impurities, or how energy leakage affects wave dynamics in Schrödinger’s equation. These are effects that can be easily realized and seen in this system, by deliberately perturbing the pendula motion in a controlled manner.

 

Left to right: Prof. Shlomi Reuveni, Ph.D. student Ofir Blumer & Dr. Barak Hirshberg

Research

Mar 17th, 2024
Could Restarting Change the Game for Chemical Research?

Not only in Information Technology: Restart Also Works in Chemical Simulations

  • Exact Sciences

A new study from Tel Aviv University discovered that a common practice in Information Technology can also be applied in chemistry. Researchers found that to enhance the sampling in chemical simulations, all you need to do is stop and restart.  The research was led by Ph.D. student Ofir Blumer, in collaboration with Professor Shlomi Reuveni and Dr. Barak Hirshberg from the Sackler School of Chemistry at Tel Aviv University. The study was published in the journal Nature Communications.

 

If We Could Turn Back Time

 

The researchers explain that molecular dynamics simulations are like a virtual microscope. They track the motion of all atoms in chemical, physical, and biological systems such as proteins, liquids and crystals. They provide insights into various processes and have different technological applications, including drug design. However, these procedures can only depict events slower than one-millionth of a second, so they can't show slower processes like protein folding or crystal nucleation. This limitation, known as the timescale problem, is a great challenge in the field.

 

Ph.D. student Ofir Blumer: “In our new study we show that the timescale problem can be overcome by stochastic resetting of the simulations. It seems counterintuitive at first glance – how can the simulations end faster when restarted? Yet, it turns out that reaction times vary considerably between simulations. In some simulations, reactions occur rapidly, but other simulations get lost in intermediate states for long periods. Resetting prevents the simulations from getting stuck in such intermediates and shortens the average simulation time”.

 

The researchers also combined stochastic resetting with Metadynamics, a popular method to expedite the simulations of slow chemical processes. The combination allows greater acceleration than either method separately. Moreover, Metadynamics relies on prior knowledge. To speed up the simulation, it's essential to know the reaction coordinates. The combination of Metadynamics with resetting reduces the dependency on prior knowledge significantly, saving time for practitioners of the method. Finally, the researchers showed that the combination provides more accurate predictions of the rate of slow processes. The combined method was used to enhance simulations of a protein folding in water successfully and it is expected to be applied to more systems in the future. 

A Lurking Crow near Mexico Building

Research

Mar 10th, 2024
Bye Bye Birdie: How Will Crows Survive Without Us?

When the Humans Are Away, Do the Crows Still Play?

  • Life Sciences

A new study from Tel Aviv University examined what happens to birds that are accustomed to living around humans, when their habitat is suddenly emptied of the presence of humans. The study found that when humans are suddenly absent from the urban environment, the activity of the crows and ringneck parakeets that “live” in the area reduces significantly. Conversely, the graceful prinias, who are generally considered shy, increased their activity.

 

Bird's Eye View

Among other birds, the researchers tested crows, ringneck parakeets (also known as rose-ringed parakeets) and graceful prinias – and the findings are surprising: while the crows and ringneck parakeets, who are characterized by their tendency to “follow” humans, are already accustomed to the noises they make and feed on their food scraps, decreased their activity, the graceful prinias, which are considered shy, actually increased their activity in the same area.

 

A prinia bird leaninn on a branch

A prinia bird leaninn on a branch.

 

The research was conducted under the leadership of research student Congnan Sun, Dr. Arjan Boonman and Prof. Yossi Yovel, head of The Sagol School of Neuroscience and a member of The School of Zoology at TAU, in collaboration with Prof. Assaf Shwartz from the Landscape Architecture Department at the Technion. The study’s results were published in ELIFE magazine.

 

Birdemic: A Lockdown Story

As part of the current study, the researchers took advantage of the first COVID-19 lockdown to test the interrelationship between man and nature, and placed 17 recording wide-band sensitive microphones in the Yarkon Park and the streets adjacent to it in northern Tel Aviv. With the help of artificial intelligence, an analysis of the recordings from the first days of the lockdown until 10 days after its end (March 25 to May 28) showed that the activity of the crows and ringneck parakeets was significantly lower (the calls from the crows in the park decreased by about 50% during the lockdowns and the chirping of ringneck parakeets in the park dropped by about 90%). In contrast, the graceful prinias actually benefited from the absence of people and increased their presence by about 12%.

 

Prof. Yossi Yovel explains: “When the first COVID-19 lockdown began, we, like many researchers, in many fields, identified a rare opportunity to conduct field experiments that would examine how animals behave in the absence of humans. In general, many studies indicated the return of species to habitats that humans had ‘abandoned’ because of the coronavirus, but most of these studies were carried out through human observation, which obviously requires humans, who are, as mentioned, the factor whose effect we want to examine. We decided to use microphones to allow us to monitor the activity of birds while humans aren’t present, and to disperse them densely throughout parks and residential neighborhoods. We chose the Yarkon Park area, heading south until Arlozorov Street, and we placed 17 microphones at a distance of about 500 meters away from each other. We chose the ‘old north’ neighborhood of Tel Aviv because it is an urban area adjacent to a park, to enable a comparison between the activity of the birds in a park and the activity of the birds in a city”.

 

Cry of the Crow

The researchers examined the changes in the presence of three particularly common and particularly loud bird species, which differ from each other in the extent to which they exploit humans: hooded crow, ringneck parakeet and graceful prinia. The hooded crow is classified as a “human-following species,” that is, it stays near humans and feeds on their food scraps. The ringneck parakeet is an invasive species, it also follows humans. The graceful prinia is classified as “adaptive” – it adapts itself to humans, and knows how to get along in an urban environment, but does not feed on humans’ food scraps and prefers to avoid their company.

 

 

In total, the researchers recorded 3,234 hours containing around 250,000 bird calls, using artificial intelligence to identify the calls and the birds that made them. During the lockdown, human activity in the residential areas increased by 49% and human activity in the Yarkon Park – while leaving homes to go to parks was still prohibited - decreased by 31%.

 

"First, we found that the overall activity of the birds, regardless of COVID-19, is 53% higher in the parks than in the streets adjacent to them", explains Prof. Yuval. "The parks are a center of activity for birds, and that is always true. On the other hand, a complex picture emerges from the lockdown period. The crows and ringneck parakeets, which usually subsist on leftover food from people in the park, searched for other avenues. The calls from the crows in the park decreased by about 50%, and the chirping of the ringneck parakeets in the park dropped by around 90%. Conversely, the shy graceful prinia, an outstanding adaptor, increased its activity by about 12%. These findings highlight the fact that there are animals that depend on us in the city, as well as the flexibility of these animals and the complexity and diversity of the urban ecosystem".

 

Research

Mar 7th, 2024
Summer Glow: How Sun Exposure Boosts Fertility in Women Ages 30-40

Exposure to The Sun's UV Radiation May Have a Positive Effect on Fertility in Women Aged 30-40

  • Medicine

A research team from Tel Aviv University and the Sheba Medical Center at Tel Hashomer investigated seasonal fluctuations in AMH (anti-Müllerian hormone) levels. Their pioneering study revealed that during the summer, women of a late reproductive age — between the ages of 30 and 40 — experience increased secretion of the hormone from their ovaries.

 

This phenomenon is suggested to be attributed to heightened exposure to ultraviolet (UV) radiation from the sun. The groundbreaking research was led by Prof. Carmit Levy of the Department of Human Genetics and Biochemistry, in a team effort of Ph.D. student Roma Parikh and Prof. Yftach Gepner of the School of Public Health, all from the Faculty of Medicine at Tel Aviv University and Dr. Ruth Percik from the Institute of Endocrinology at Sheba Medical Center. The results of the study were published in the journal Steroids.

 

“The ovaries secrete the anti-Müllerian hormone, and its level in the bloodstream is linked to ovarian function,” explains Dr. Percik. “While the hormone level is specific to an individual woman at a given point in time, and does not provide a definitive assessment of the status of her fertility, evaluating its value, trend, and comparison to the age group is the best indicator of fertility that we have. For this reason, every woman who wants to get pregnant, or is trying to, is sent for an AMH test. In Israel, all of these tests are directed to the central laboratory in Sheba. Our research group investigated the seasonal variability of the AMH tests to gauge how the ovaries respond to UV radiation”.

 

Moderation in Sun Exposure: Key to Fertility Health

 

 

The researchers compared the AMH results of 2,235 Israeli women to the recorded levels of UV radiation. For younger women, aged 20-29, no statistical relationship was found between UV exposure and AMH level. On the other hand, among older fertile women, aged 30 to 40, a statistically significant seasonal pattern emerged: These women, whose egg reserves are in decline, responded positively to sun exposure.

 

“Based on our prior studies, we can affirm that sun exposure increases metabolism, as well as sexual appetite and behavior, and (at least in animal models) enlarges the ovaries and extends the estrus period” explains Prof. Levy.

 

“This is a preliminary, pioneering human epidemiological study, and we need to be cautious about inferring a causal relationship between fertility in women and exposure to UV radiation. Humans are not the same as mice. However, we are also animals, our hairless nature makes us even more sensitive to solar radiation. Our research suggests that the female reproductive system is indeed more fertile in the summer, but we still have no information on the mechanism or actual success rates”, she continues.

 

Particularly interesting is the absence of this effect among younger women in their 20s. According to Dr. Percik, this may be attributed to the ample egg reserve found in young women. “Based on my interpretation of the findings, women at the onset of their reproductive age are less in need of signals from the sun, which affect hormonal pathways that have not yet been sufficiently studied. They are less impacted or dependent on the forces of nature in the context of fertility. In contrast, older ovaries need optimal environmental factors to function. In fact, this effect was even more pronounced among women aged 35 and older. Of course, there are caveats: Exposure to the sun's UV radiation should always be done in moderation, and further research is required to determine whether such exposure actually helps fertility, and how much exposure is needed”.

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