Compact Portable Defibrillator Developed

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Compact Portable Defibrillator Developed by Technion Students Wins BizTEC 2021 Entrepreneurship Program

 Technion President Prof. Uri Sivan, entrepreneurs, and venture capital industry representatives attended the final event of the BizTEC Entrepreneurship Program at the Technion

Since its establishment in 2004, graduates of the program have raised a total of more than $1 billion

First prize winners. Right to left: Ohad Yaniv, Eyal Kellner, Yaron Arbel, Alon Gilad, Idan Shenfeld, Ravit Abel and Prof. Ezri Tarazi

The Defi team, established by Technion students, won first prize and $10,000 in the BizTEC 2021 entrepreneurship competition, which took place in Tel Aviv. The prize was awarded to the team members for the development of a compact portable defibrillator, which is inexpensive and easy to use.

Sudden Cardiac Arrest is caused when the heart’s electrical system malfunctions. The heart stops beating properly, and its pumping function is “arrested,” or stopped. Automated External Defibrillators (AED) are ambulatory devices designed to automatically analyze the patient’ s heart rhythm and, if it is found to be in need for fibrillation, deliver the electric pulse (or “shock”) to the heart in order to restore the normal heart rhythm. These devices are typically housed in a briefcase container, mounted to wall on offices and public places. Hand carried AED’s are expensive, and their size and shape impede portability. The product on which the Defi team members are working is a cost-effective, accessible alternative to the traditional defibrillator that would significantly decrease its size and price and making AEDs more abundant in society.

The members of the team are Ravit Abel, graduate of the Wolfson Faculty of Chemical Engineering, Idan Shenfeld, a graduate of the Henry and Marilyn Taub Faculty of Computer Engineering in the Rothschild-Technion Program for Excellence, and Alon Gilad, a mechanical engineer studying for his master’s degree in the Faculty of Biomedical Engineering. The team was accompanied throughout the accelerator process by Ichilov Hospital’s Chief Information Officer, Eyal Kellner, and the Director of Ichilov’s Cardiovascular Research Center, Professor Yaron Arbel. Several months ago, the team took first place in the iTrek competition, which was held at the Technion and at the Joan and Irwin Jacobs Technion-Cornell Institute at Cornell Tech.

Today, the BizTEC Entrepreneurship Program is part of t-Hub, the Technion Entrepreneurship and Innovation Center, headed by Professor Ezri Tarazi, under the leadership of Ohad Yaniv, who heads the BizTEC accelerator program and startup programs.

The BizTEC program was founded in 2004 to cultivate novice entrepreneurs seeking to develop deep technologies that require interdisciplinary collaboration and in-depth knowledge infrastructure. It provides participating teams with close professional guidance by mentors from academia and industry. In the 17 years of the program’s existence, its graduates have founded dozens of active companies that have collectively raised more than $1 billion, including Breezometer, Augmedics, Windward, Houseparty, and Presenso. This year, around 100 teams applied for the program, and of them, 37 were accepted. Eleven teams made it through to the finals and presented their developments to the audience.

The final event was attended by Technion President Professor Uri Sivan, numerous entrepreneurs, and senior representatives of the venture capital industry in Israel, many of them Technion alumni. They included former Minister of Science and Technology and entrepreneur Izhar Shay, Ormat founders Dita and Yehuda Bronicki, etrepreneur Yossi Vardi, Dadi Perlmutter, who served as Executive Vice President of the global Intel Corporation, Playbuzz founder Shaul Olmert, former CEO of Microsoft Israel, Yoram Yaacovi, entrepreneur Dan Vilenski.

Technion President Prof. Uri Sivan opened the event and said: “In the past few years we recognized that entrepreneurship is a far broader field than tech entrepreneurship or business entrepreneurship. Entrepreneurship is a state of mind that can be applied in every sphere of the lives of us all and is tightly connected with leadership. In recent years, here at the Technion we developed numerous social entrepreneurship programs, meaning groups of people that go out to the community and use entrepreneurial tools and entrepreneurial thinking to better the community’s condition, working together with the community. I thank Dita and Yehuda Bronicki who support the program, not only materially but also spiritually. Their spirit is instilled in every aspect of the entrepreneurship program.”

“As the Technion’s leading entrepreneurship program, BizTEC well reflects the integration of entrepreneurial leadership as a substantial part of the study experience,” said Prof. Ezri Tarazi, Head of the Technion Entrepreneurship and Innovation Center (t-Hub). “It furnishes participants with tools for the assimilation of deep technology in meaningful applications that are connected to the global challenges we face in human health, sustainability and the digital world. This event, hosted by t-Hub and attended by senior members of the Israeli hi-tech industry, is proof of the Technion’s continuing centrality to Israel’s economy.”

“BizTEC is a small, special place that enables teams to come in with just an idea, and in less than six months, acquire all the tools they need to turn it into reality,” said Ohad Yaniv, head of the accelerator program and startup programs. “Starting with building the business model, through validation, creating proof of concept, building a presentation, all the way to the pilot phase, first customer acquisition and even the first investment. Compared to any other accelerator in Israel, and even on an international level, its results are exceptional.”

Second place winners with Dita Bronicki.

Two teams took second place: BrainSense, which developed a system that monitors stroke events by identifying changes in brain activity and whose members are Technion students; and Oral Detect, which developed a home system for the early detection of tooth decay and won the BME-Hack Biomedical Engineering Hackathon that took place at the Technion earlier this year. Third place was taken by Soltrex, a team of Technion graduates that developed a fully autonomous technology for the cleaning and operation of solar panels.

 

Smart Wound Dressing

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Smart Wound Dressing

Instead of sutures, a self-healing antibacterial polymer; instead of examining the wound, integrated smart monitoring

“Sutures? That’s practically medieval!”

Professor Hossam Haick

It is a staple of science fiction to mock sutures as outdated. The technique has, after all, been in use for at least 5,000 years. Surely medicine should have advanced since ancient Egypt. Professor Hossam Haick from the Wolfson Department of Chemical Engineering at the Technion has finally turned science fiction into reality. His lab succeeded in creating a smart sutureless dressing that binds the wound together, wards off infection, and reports on the wound’s condition directly to the doctors’ computers. Their study was published in Advanced Materials.

Current surgical procedures entail the surgeon cutting the human body, doing what needs to be done, and sewing the wound shut – an invasive procedure that damages surrounding healthy tissue. Some sutures degrade by themselves – or should degrade – as the wound heals. Others need to be manually removed. Dressing is then applied over the wound and medical personnel monitor the wound by removing the dressing to allow observation for signs of infection like swelling, redness, and heat. This procedure is painful to the patient, and disruptive to healing, but it is unavoidable. Working with these methods also mean that infection is often discovered late, since it takes time for visible signs to appear, and more time for the inspection to come round and see them. In developed countries, with good sanitation available, about 20% of patients develop infections post-surgery, necessitating additional treatment and extending the time to recovery. The figure and consequences are much worse in developing countries.

Self-healing, antibacterial, and multifunctional wound dressing in action

How will it work with Prof. Haick’s new dressing?

Prior to beginning a procedure, the dressing – which is very much like a smart band-aid – developed by Prof. Haick’s lab will be applied to the site of the planned incision. The incision will then be made through it. Following the surgery, the two ends of the wound will be brought together, and within three seconds the dressing will bind itself together, holding the wound closed, similarly to sutures. From then, the dressing will be continuously monitoring the wound, tracking the healing process, checking for signs of infection like changes in temperature, pH, and glucose levels, and report to the medical personnel’s smartphones or other devices. The dressing will also itself release antibiotics onto the wound area, preventing infection.

Photo of the sensing part of MFDW

“I was watching a movie on futuristic robotics with my kids late one night,” said Prof. Haick, “and I thought, what if we could really make self-repairing sensors?”

Dr. Ning Tang

Most people discard their late-night cinema-inspired ideas. Not Prof. Haick, who, the very next day after his Eureka moment, was researching and making plans. The first publication about a self-healing sensor came in 2015 (read more about it on the Technion website here). At that time, the sensor needed almost 24 hours to repair itself. By 2020, sensors were healing in under a minute (read about the study by Muhammad Khatib, a student in Prof. Haick’s lab here), but while it had multiple applications, it was not yet biocompatible, that is, not usable in contact with skin and blood. Creating a polymer that would be both biocompatible and self-healing was the next step, and one that was achieved by postdoctoral fellow Dr. Ning Tang.

The new polymer is structured like a molecular zipper, made from sulfur and nitrogen: the surgeon’s scalpel opens it; then pressed together, it closes and holds fast. Integrated carbon nanotubes provide electric conductivity and the integration of the sensor array. In experiments, wounds closed with the smart dressing healed as fast as those closed with sutures and showed reduced rates of infection.

“It’s a new approach to wound treatment,” said Prof. Haick. “We introduce the advances of the fourth industrial revolution – smart interconnected devices, into the day-to-day treatment of patients.”

Concept of MFWD, which can inhibit bacterial growth, close a wound in sutureless manner via biocompatible elastomer having self-healing ability, and monitor healing status by detecting wound-related biomarkers.

Prof. Haick is the head of the Laboratory for Nanomaterial-based Devices (LNBD) and the Dean of Undergraduate Studies at the Technion. Dr. Ning Tang was a postdoctoral fellow in Prof. Haick’s laboratory and conducted this study as part of his fellowship. He has now been appointed an associate professor in Shanghai Jiao Tong University.

For the article in Advanced Materials click here

Improvement on the effect of anti-cancer drugs

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Medical technology developed at the Technion improves the effect of anti-cancer drugs:

The technology, based on the Nano-Ghosts platform, makes it possible to reduce the drug dose a million-fold without reducing its efficacy

Prof. Marcelle Machluf

Researchers in the Faculty of Biotechnology and Food Engineering at the Technion developed a technology that inhibits development of melanoma using one-millionth of the active ingredient. The study, published in Advanced Functional Materials, was led by Prof. Marcelle Machluf, dean of the faculty, and PhD student Lior Levy.

Immunotherapy in action. This development is a significant breakthrough in the field of immunotherapy – an innovative medical approach that has become one of the most promising trends in cancer treatment. The approach is based on the ability of the body’s own immune system to destroy cancer cells. This system can do that more accurately and specifically than synthetic anti-cancer drugs. However, since the malignant tumor is heterogeneous and evasive, it can sometimes fool the immune system, and this is where science enters the picture, with new tools that help the immune system deal with this challenge.

Lior Levy

TRAIL protein. At the core of this new development is a protein called TRAIL, which exists in the body’s immune system and knows how to induce apoptosis (programmed cell death) of cancer cells. In other words, it is a Tumor Necrosis Factor (TNF). Another advantage: it is selective, meaning it only affects cancer cells, a highly desirable feature in anti-cancer treatment. The application of TRAIL in immunotherapy has so far encountered various technical challenges, including the absorption of the protein in the body, its distribution (pharmacokinetics), and the fact that it does not survive for very long. This study offers a solution to these problems.

Nano-Ghosts technology. The development presented in the Technion researchers’ article is based on original technology developed by Prof. Machluf in her years at the Technion: Nano-Ghosts. The platform is produced by emptying specific biological cells (mesenchymal stem cells) in a way that leaves only the cell membrane and reducing their size to a nanometer scale. Any drug can be inserted into the membrane and injected directly into the bloodstream. Because the body’s immune system treats nano-ghosts as natural cells, it delivers them to the affected site. They do not release the drug on the way, and therefore do not harm healthy tissue. They target the malignant tissue, where they deliver the drug into the tumor cells.

Integration. The study integrates the three aforementioned factors: the immunotherapy concept, the TRAIL protein, and the Nano-Ghost technology developed by Prof. Machluf. The result: a drug delivery system with the active protein on its outer layer, which allows reduction of the drug dosage by a factor of a million while maintaining the same treatment effect.

A schematic description of preparing Nano-Ghosts from cells that underwent genetic or metabolic manipulation and now carry the TRAIL protein. These cells, with Nano-Ghost targeting for cancer and with the TRAIL protein, can reach the cancer site and fight effectively while using one millionth the concentration of the active ingredient required without this system.

According to Prof. Machluf, “this integration turns the Nano-Ghost platform from a “taxi” that delivers the drug to the target into a “tank” that participates in the war. The integrated platform delivers the drug to the tumor and enables a significant reduction in drug dosage yet still does the job. We also showed that our method does not harm healthy cells.”

The technology was demonstrated on cells in the lab and on human cancer cells in mice. The researchers estimate that this new strategy, which was demonstrated in their study on a melanoma model, will also be effective on other types of cancer.

 

For the article in Advanced Functional Materials click here

Selective Filtration

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Selective Filtration

Membranes developed at the Technion and Germany enable precise selective separation of nanoparticles

Researchers from the Technion – Israel Institute of Technology and the Helmholz-Zentrum Hereon Center in Germany have developed a new concept for fabricating membranes for on-demand nanoparticle separation with high selectivity. These membranes are relevant for diverse applications that include pharmaceutical processing, materials separation, water purification, and wastewater treatment.

Assistant Professor Tamar Segal-Peretz

Published in Advanced Materials, the research study was led by Assistant Professor Tamar Segal-Peretz and Ph.D. student Assaf Simon of the Wolfson Faculty of Chemical Engineering at the Technion, together with Dr. Zhenzhen Zhang and Professor Volker Abetz of the Helmholz-Zentrum Hereon Research Center.

High-selectivity molecular separation is a common process in nature that occurs, for example, in cell membrane channels. Membrane channels separate the interior of the cell from its outside environment and regulate which materials can pass into and out of the cell. Inspired by nature, numerous research groups have attempted to develop similar membrane channels that enable precise filtration of various materials for diverse industrial applications. But synthetic fabrication of such membranes, with high levels of well-ordered pores, and high uniformity and selectivity, poses a complex engineering challenge, made even more complex when the membranes are intended for extremely small nanoparticle separation.

Assaf Simon

The Technion and Helmholz-Zentrum Hereon researchers succeeded in fabricating such membranes using block copolymers – spontaneously self-assembled polymer molecules, in combination with metal oxide growth on and within the block copolymer pores. The process developed by the researchers provides an excellent method for precisely tuning the pore size as well as other properties of the membrane. In addition, the metal oxide is an ideal base for incorporating functional groups on the membrane surface, granting it unique properties, such as electric charge and hydrophobicity (water repellency). These membranes exhibited superior performance in the separation of nanoparticles based on size, charge, and/or hydrophobicity.

On the right: The fabrication process of the membranes. Metal oxides are grown within the membrane channels to precisely tunes the pore size, after which a reaction is generated to create a membrane possessing unique physical properties. On the left: Cross-sectional image of the membrane, showing the incorporation of the metal oxides on the block copolymer membranes.

Prof. Segal-Peretz estimates the breakthrough will provide various industries with a new, versatile, and accurate tool for the filtration of molecules, pollutants, and other particles.

 

Click here for the paper in Advanced Materials

AI improves the accuracy of antibiotic selection for the treatment of UTI

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Maccabi Healthcare Services and the Technion: AI improves the accuracy of antibiotic selection for the treatment of UTI

Shortly after the AI-based advanced tool was introduced, there was a 35% drop in the need to switch antibiotics. The technology was developed by the Technion and Maccabi Healthcare Services

Doctors at Maccabi Healthcare Services have recently begun to work with an AI-based predictive algorithm developed by the Technion – Israel Institute of Technology together with KSM (Kahn-Sagol-Maccabi), the Maccabi Research and Innovation Center. The new algorithm advises doctors in the process of deciding on personalized antibiotic treatment for patients.

The first diagnosis on which Maccabi chose to focus is urinary tract infection (UTI) – the most common bacterial infection among women. Around 30% of the females suffer from the infection at least once during their lifetime, and up to 10% experience recurrent infections. Until now, in most cases general treatment has been administered based on clinical guidelines and medical judgment. Sometimes, the bacteria prove to be antibiotic resistant, resulting in the need to change the treatment plan.

Since the new algorithm was introduced, Maccabi doctors have treated tens of thousands of cases, and there has been a drop of around 35% in the need to switch antibiotics following the development of bacterial resistance to the drug prescribed. This is significant because accuracy in the choice of antibiotic is far greater thanks to the new technology. In light of the success of this new development in the treatment of UTI, Maccabi has begun working on the development of additional detection systems that will help to contend with other infectious diseases that require personalized treatment with antibiotics.

How does it work?

The automated system recommends the most suitable antibiotic treatment for the patient to the doctor, based on clinical guidelines and other criteria such as age, gender, pregnancy status, residence in an assisted living facility, and personal history of UTI and antibiotics administered.

The unique algorithm was developed by Professor Roy Kishony and Dr. Idan Yelin of the Technion Faculty of Biology, in cooperation with KSM, Maccabi’s Research and Innovation Center, headed by Dr. Tal Patalon, and was introduced and implemented among Maccabi’s doctors by the HMO’s Medical Informatics team and Chief Physician’s Department. According to Prof. Kishony, “The algorithm we developed together with Maccabi’s experts is a major milestone in personalized medicine on the way to AI-based antibiotic treatments, which are personally tailored to the patient according to the prediction of treatment response and mitigate the development of resistant bacteria.”

Dr. Shira Greenfield, Director of Medical Informatics at Maccabi Healthcare Services, said, “The significance of administering personalized antibiotic treatment is that it lowers the risk of antibiotic resistance developing – a global problem which all healthcare entities are working to solve.”

We’re Losing Oxygen, and It’s Great!

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We’re Losing Oxygen, and It’s Great!

 Researchers in the Technion Department of Materials Science and Engineering have succeeded in changing a material’s electrical properties by vacating an oxygen atom from the original structure. Possible applications include electronic-device miniaturization and radiation detection

What do ultrasound imaging of a fetus, cellular mobile communication, micro motors, and low-energy-consumption computer memories have in common? All of these technologies are based on ferroelectric materials, which are characterized by a strong correlation between their atomic structure and the electrical and mechanical properties.

 

Dr. Hemaprabha Elangovan, Assistant Professor Yachin Ivry and Ph.D. student Maya Barzilay

Technion – Israel Institute of Technology researchers have succeeded in changing the properties of ferroelectric materials by vacating a single oxygen atom from the original structure. The breakthrough could pave the way for the development of new technologies. The research was headed by Assistant Professor Yachin Ivry of the Department of Materials Science and Engineering, accompanied by postdoctoral researcher Dr. Hemaprabha Elangovan and Ph.D. student Maya Barzilay, and was published in ACS Nano. It is noted that engineering an individual oxygen vacancy poses a considerable challenge due to the light weight of oxygen atoms.

In ferroelectric materials, a slight shift of the atoms causes significant changes in the electric field and in the contraction or expansion of the material. This effect is the result of the fact that the basic repeating unit in the material contains atoms that are organized in an asymmetric structure.

In order to explain this further, the researchers use the seminal ferroelectric material, barium titanate, the atoms of which form a cubic-like lattice structure. In these materials, a unique phenomenon occurs: the titanium atom draws away from the oxygen atoms. Since titanium is positively charged and oxygen is negatively charged, this separation creates polarization, or in other words, an electric dipole moment.

In the micrograph: Image of the structure before (on the right) and after (left) removing an oxygen atom.

A cubic lattice has six faces, so the charged atoms move into one of six possibilities. In different parts of the material, a large number of neighboring atoms shift in the same direction, and polarization in each such area, which is known as a ferroelectric domain, is uniform.  Traditional technologies are based on the electric field created in those domains. However, in recent years, a great deal of effort has been directed at minimizing the device size and using the borders, or walls, between the domains rather than the domains themselves, and thus converting the devices from three-dimensional structures to two-dimensional structures.

The research community has remained divided in opinion as to what happens in the two-dimensional world of the domain walls: How is the border between two domains with different electric polarization stabilized? Is the polarization in domain walls different to the polarization in the domains themselves? Can the properties of the domain wall be controlled in a localized manner? The great interest in addressing these questions stems from the fact that a ferroelectric material in its natural form is an excellent electric insulator. However, the domain walls may be conducting electrically, thus forming a two-dimensional object that are controllable by will. This phenomenon encompasses the potential to reduce significantly the energy consumption of data storage and data processing devices.

In this project, the researchers succeeded in deciphering the atomic structure and electric field deployment in domain walls at the atomic scale. In their recent article, they corroborate the assumption that domain walls allow for the existence of a two-dimensional border between domains as a result of partial oxygen vacancy in areas that are common to two domains, thus enabling greater flexibility in the deployment of the local electric field. They succeeded in engineeringly inducing an individual oxygen atom vacancy and demonstrated that this action creates opposing dipoles and greater electric symmetry – a unique topological structure called a quadrupole.

With the aid of computer simulations by Shi Liu of Westlake University in China, the researchers demonstrated that engineering the oxygen atom vacancy has a great impact on the electrical properties of the material not only at the atomic scale, but also at the scale that is relevant to electronic devices – for example, in terms of electrical conductivity. The significance is that the present scientific achievement is likely to be of help in miniaturizing devices of this kind as well as reducing their energy consumption.

Collaboration with researchers from the Negev Nuclear Research Center, the Technion research group also demonstrated that oxygen vacancies can be engineered by exposing the material to electronic radiation. Consequently, in addition to the technological potential of the discovery in electronics, it may also be possible to utilize the effect for radiation detectors, allowing for the early detection – and prevention – of nuclear accidents, such as the one that happened in 2011 in Fukushima, Japan.

The research, which was carried out at the Electron Microscopy Center in the Faculty of Materials Science and Engineering, was funded by the Israel Science Foundation and the Pazy Foundation. The Nano and Quantum Functional Structures Laboratory, headed by Asst. Prof. Ivry, is supported by the Zuckerman STEM Leadership Program.

For the article in ACS Nano click here

 

Molecule that inhibits degenerative processes related to Alzheimer’s disease

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 Researchers at the Technion developed a molecule that inhibits degenerative processes related to Alzheimer’s disease

Professor Galia Maayan

Researchers at the Technion – Israel institute of Technology, in collaboration with researchers from CNRS, recently published findings about the development of an artificial molecule that may inhibit the development of Alzheimer’s disease. The molecule breaks down the toxic chemical complex Cu–Aβ, thus inhibiting the cell death that is thought to be related to Alzheimer’s. The study was led by Professor Galia Maayan and doctoral student Anastasia Behar from the Schulich Faculty of Chemistry, in collaboration with Prof. Christelle Hureau from the Laboratoire de Chimie de Coordination du CNRS, Toulouse, France.

Copper ions are a key component of the structure and function of various cells in the body. But their accumulation can lead to cell toxicity, causing dangerous conditions such as oxidative stress, cardiovascular disorders, and degenerative diseases of the brain, including Alzheimer’s.

Doctoral student Anastasia Behar

One of the mechanisms involved in the development of Alzheimer’s is the formation of free radicals that damage the brain cells. These are oxidizing agents formed, among other things, by Cu–Aβ, a complex of copper and amyloid beta. It is already known that the breakdown of this complex, and the removal of copper from the amyloid, prevents cell death, followed by the inhibition of the disease. The extraction of the copper is done by chelation – using molecules that bind the copper ions and extract them from the amyloid.

However, this is not a simple challenge, because the chelators must meet several critical chemical and kinetic conditions, including stability and resistance to oxidation-reduction reactions. It is also important that the chelator does not bind zinc ions during the copper extraction process, as they are also essential for neuron function (but do not cause toxicity when they are bound to the amyloid); if the chelator does not bind the zinc, it can continue to bind the copper ions, but if it binds zinc, copper binding will be inhibited.

In the figure, from left to right: Oxidation of copper ions in an amyloid complex (that also contains zinc ions) leads to the formation of a toxic amyloid complex and harmful oxidizing agents (ROS). The water-soluble chelator extracts the copper ion from the amyloid complex

The Technion and CNRS researchers report in the Angewandte Chemie on the successful development of a new artificial chelator that meets all these requirements. The chelator, called P3, is a peptide-like water-soluble synthetic molecule that performs its task selectively; it strongly binds copper and forms the complex CuP3, extracting the copper from the amyloid. By doing so, it inhibits and even suppresses the formation of harmful oxidizing agents, without creating new oxidation processes. Although it binds zinc ions and even extracts them from the amyloid faster than it extracts the copper ions, the binding to zinc is weaker, making the zinc-amyloid complex unstable, so in practice P3 mostly binds copper ions. by creating a new, stable complex, and inhibits the formation of harmful oxidizing agents (NO ROS), thereby neutralizing amyloid toxicity.

Click here for the paper in Angewandte Chemie

 

An Inflammation to Remember

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An Inflammation to Remember

Technion scientists uncover a physiological mechanism of psychosomatic illness

Your phone pings. It’s a notification from your friend, who you just went out for a drink with last night. According to her text, she has just tested positive for COVID-19. You start feeling your throat, you sneak a short cough, and start to feel your body temperature rising. But then you calm down (after receiving your negative COVID results, of course) and realize these feelings were all in your head. But what if this is exactly it – what if there were indeed neurons in the brain that could induce a sensation of illness, or even an actual disease?

Psychosomatic disorders are described as diseases emerging with no apparent biological cause, and often include a strong emotional component as a trigger. In a study recently published in Cell, Technion scientists explore the brain’s potential to cause diseases on its own. Specifically, they induced inflammation in mice, and then triggered the neurons in the brain that were active during the initial inflammation.

Tamar Koren (right) and Professor Asya Rolls

The study was conducted by the research group of Associate Professor Asya Rolls from the Technion Ruth and Bruce Rappaport Faculty of Medicine, led by Tamar Koren, an M.D./Ph.D. student in the lab. They showed that during colon inflammation, several brain regions exert enhanced neuronal activity, one of which was the insular cortex (insula). The insula is an area in the brain responsible for interoception, that is the sense of the body’s physiological state. This includes hunger, thirst, pain, and heart rate.

The researchers postulated that if report of inflammation in some area of the body is stored somewhere in the brain, this area responsible for interoception would be involved. Armed with this hypothesis, they induced in mice an inflammation in the colon and using genetic manipulation techniques, “captured” groups of neurons in the insular cortex that showed increased activity during the inflammation. Once the mice were healthy, the researchers triggered these “captured” neurons artificially. Without any outside stimulus other than this triggering of cells in the brain, inflammation re-emerged, in the exact same area where it was before. “Remembering” the inflammation was enough to reactivate it.

If the brain can generate disease, is it possible that it can also turn it off?

Scientific photo: Upper panel: Insular neurons (in red) that were captured during colitis and reactivated (in green) upon recovery. Lower panel: Colon sections showing white blood cells (in red) present in the tissue of a mouse after insular neurons reactivation (Gq, right) and its non-activated control (Sham, left).

In a similar manner, Tamar also demonstrated the opposite effect: in mice with active inflammation, suppressing the neurons that remembered it produced immediate reduction in the inflammation. Although this was a basic study in mice, and there are multiple challenges in translating the concept to humans, these discoveries open a new therapeutic avenue for treating chronic inflammatory conditions such as Crohn’s disease, psoriasis, and other autoimmune conditions, by attenuating their memory trace in the brain.

The Research group of Professor Asya Rolls

“There are evolutionary advantages to such a connection,” said Prof. Rolls in explaining the strange phenomenon whereby the immune system should be activated by memory alone, without an outside trigger. “The body needs to respond to infection as quickly as possible before the attacking bacteria or viruses can multiply. If certain activity, for example consuming particular foods, has exposed the body to infection and inflammation once, there is an advantage to gearing up for battle when one is about to engage in the same activity again. A shorter response time would allow the body to defeat the infection faster and with less effort. The problem of course is when such an effective mechanism goes out of control and can on its own generate the disease.”

The group’s findings have broad implications for understanding the way the human mind and body affect each other, but also more immediate implications for understanding and treating illness with a psychosomatic element, like irritable bowel syndrome, and even autoimmune diseases and allergies.

The study was done in collaboration with Dr. Kobi Rosenblum, of the University of Haifa and Dr. Fahed Hakim, of EMMS Hospital, Nazareth. This work was supported by the European Research Council (ERC) Starting Grant, the Allen and Jewel Prince Center for Neurodegenerative Disorders of the Brain, the Howard Hughes Medical Institute (HHMI), and the Wellcome trust.

 

For the full article in Cell click here.

Click here for video demonstrating the research

Scientists Discover Emergency Pathway to Help Human Cells with Protein Damage Survive

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Scientists Discover Emergency Pathway to Help Human Cells with Protein Damage Survive

Cell proteins damaged by oxygen radicals can be chemically “tagged” for elimination, but an “emergency pathway” bypasses strict protocol and can eliminate even without the need for prior tagging.

An international research team headed by Technion scientists has found an alternative manner for eliminating damaged proteins when the cells are impaired by “oxygen radicals,” as can happen in failing human hearts where there is poor cell respiration and cells become oxygen depleted, or suffer “hypoxia,” because of poor oxygen uptake.

Significantly, the researchers discovered that there can be a shift from the tightly controlled process of eliminating proteins in the cells to a less strict mechanism when cells enter an “emergency protocol.” This shift can “clear up” the toxic proteins before their toxicity levels get too high.

Their study was published on 26 October 2021 in Nature Communication. To carry out their study, the researchers investigated several “proteasomes,” protein complexes that work by a chemical reaction to degrade unneeded or damaged cell proteins. The researchers found that elevated levels of one type of proteasome, 20S, appears to contribute to cell survival, even for those cells under stress from damaged proteins.

L-R: Professor Oded Kleifeld, Professor Michael Glickman and Professor Ashraf Brik

Human cells – both functional and damaged – are constantly recycled by chemically “tagging” and targeting for removal when they are under stress by the ubiquitin system (2004 Nobel Prize in chemistry). At the same time, a few proteins that are intact and functional can also be dragged into the 20S proteasome “molecular disposal unit” along with the toxic proteins that have be targeted for destruction. Nevertheless, rather than harm cells, this mode of action by 20S proteasome may aid cells in rapidly remove toxic proteins. In their conclusion, the authors raised the interesting speculation that this emergency pathway can help even damaged cells to withstand bouts of stress and allow them to “age gracefully”.

Professor Michael Glickman (left) and Professor Indrajit Sahu

To carry out the study, Technion researchers Professors Indrajit Sahu, Michael Glickman, Ashraf Brik, and Oded Kleifeld, worked with Professor Sharlene Day, from the University of Pennsylvania, and the research team of Professor Yao Cong of the Chinese Academy of Sciences in Shanghai, China.

 

Click here for the paper in Nature Communications

Technion Lab Out to Show That Medical Cannabis Isn’t One-Size-Fits-All

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Technion Lab Out to Show That Medical Cannabis Isn’t One-Size-Fits-All

A few years ago, Israel started treating severely autistic children with medical marijuana. The results were startling. Many children slept peacefully throughout the night for the first time in their lives, made eye contact, or uttered their first words. Then suddenly, some children inexplicably demonstrated self-abusive and other regressive behaviors.

What happened? It turned out that the cannabis grower changed greenhouses. Physicians thought they were prescribing the same medicine, but the new plant was as different as penicillin is from tetracycline. “Cannabis is a generic name,” said Professor Dedi Meiri, the Technion’s cannabis expert. “It’s not enough to say, ‘Take two and this will help.’”

Professor Dedi Meiri

Prof. Meiri is on a mission. He aims to understand the cannabis plant so thoroughly that a physician knows exactly what is in the medicine in order to repeat a prescription with precision. Medical marijuana with a high percentage of CBD, the non-psychoactive part of the plant, for example, is usually beneficial for reducing seizures. But recently, Prof. Meiri found some strains with high CBD that worsen seizures. “How can we repeat a successful treatment if we don’t know its active compounds? We are not blind anymore,” he said.

Prof. Meiri’s Laboratory of Cancer Biology and Cannabinoid Research in the Faculty of Biology is the largest of its kind in academia, with 44 researchers developing methods for analyzing the active compounds in over 900 different types of cannabis plants. He works with cannabis growers to identify almost every strain of marijuana grown in Israel, with the goal of matching specific strains to the diseases each affects. “When we started to work with cannabis in the lab, we found that cannabis #1 could kill colon cancer cells but did nothing for prostate cancer, while cannabis #2 killed prostate cancer but didn’t affect colon cancer,” he said.

Today, his lab has teams of researchers devoted to studying the effects of  cannabis on cancer, neurodegenerative diseases including Alzheimer’s, and immunological diseases such as multiple sclerosis. They have eight clinical trials underway, as well as preclinical trials with mice. They are also preparing to start clinical trials on leukemia patients, for whom their research is furthest along. They already understand the mechanisms by which the cannabis affects the leukemia cells in bone marrow. “Our clinical trials will focus on kids where traditional medicine is not working, and on adults whose success rate is low,” he said.

In addition, Prof. Meiri’s Technion scientists are studying our body’s naturally occurring endocannabinoids, which bind to the same receptors as cannabis. They are also building exhaustive databases that profile the compounds taken by Israel’s 60,000 medical marijuana patients, and identify treatments according to patient-class specifics. The databases will be accessible online to provide recommendations for the most suitable, safe, and effective cannabis treatment.

This is a far cry from when Prof. Meiri started working with cannabis in 2015. “We were quite alone, like pioneers in the desert,” he recalled. “Today, everybody is talking about cannabis.”