EuroTech is a strategic alliance between 6 European Universities of Science and Technology. As part of our general mission, EuroTech has formed a Covid-19 task force to utilize research and technology in the fight against the pandemic. The aim of this workshop is to inform on ongoing related projects in each University, to make knowledge and tools available for others and to form collaborations between involved scientists.
Scientific Plan (note: CET time zone)
14:00 – 14:20
Yotam Bar-On – Israel Institute of Technology (Technion)
Isolation and characterization of rare SARS-CoV-2 variants by single-genome sequencing
14:20 – 14:45
Bert Blocken – Eindhoven University of Technology (TU/e)
COVID-19 aerosol reduction by ventilation and air cleaning in a gym
14:45 – 15:10
Jean-Louis Mergny – École Polytechnique (L’X)
SARS-CoV-2 Nsp3 Unique Domain SUD interacts with Guanine quadruplexes
15:10 – 15:35
Arsen Melikov – Technical University of Denmark (DTU)
Effective reduction of airborne transmission of COVID-19 indoors
15:35 – 16:00
David Atienza – École Polytechnique Fédérale de Lausanne (EPFL)
The COUGHVID project: Is COVID-19 screening possible from cough sound?
Technion researchers have discovered how a gut microbiota deals with changes in habitat through reversible genetic inversion
How does our gut respond and adapt to changing conditions? Where does this fundamental and critical flexibility come from? Technion scientists are unraveling the genius of the gut’s microbiome, through microbiota, all the way to genetic inversion.
Assistant Professor Naama Geva-Zatorsky and doctoral student Nadav Ben-Assa of the Rappaport Faculty of Medicine, in collaboration with scientists from Harvard University, have decoded a reversible genetic inversion mechanism that helps a bacterial species of the gut microbiota deal with changes in its habitat. Their findings are published in Nucleic Acids Research, a peer-reviewed scientific journal of Oxford University Press.
Assistant Professor Naama Geva-Zatorsky (left) and doctoral student Nadav Ben-Assa
The human microbiota refers to the collection of microbes (bacteria, viruses, etc. ) that colonize the inner and outer surfaces of the human body. The human intestine contains the most abundant and diverse microbiota population.
Gut microbiota provide a fundamental coping mechanism within the dynamic environment of the gut, in which structural, mechanical, and chemical change occurs incessantly. One mechanism that helps the gut microbiota perform involves rapid, reversible changes in genomes in response to external stimuli.
The article published in Nucleic Acids Research discusses this mechanism in one of the most abundant bacterial species in the human gut, Bacteroides fragilis. This bacterium is capable of inverting a large number of defined regions throughout its genome sequence. The researchers focused on the relationship between this capability and the organism’s gene expression.
The research team examined the gene expressions of these changes (recombination) and found extensive alterations in the bacterial genome.
In the diagram: The bacterium alters its defense system (the weapon), causing a change in the surrounding sugars (the hexagons on the bacterium)
“Among other things, we discovered changes in the sugars surrounding the bacterium,” said Prof. Geva-Zatorsky. “These sugars serve as a kind of ‘identity card’ that helps the bacterium communicate with the environment. With these sugars, they also help our bodies, or more precisely, our immune system, to identify the type of bacterium present, and to respond to it. This is why we assume that changes in the gut alter that ‘identity card,’ which enables our cells to respond to the bacterium in different ways.”
The researchers emphasized that these are reversible genetic inversions, based on recombination of regions in the genome in a major system in the B. fragilis organism. Consequently, this recombination has an extensive effect on the organism’s gene expression, including various vital molecules.
Genetic analysis was performed using SMRT (single molecule real-time) sequencing – an innovative technology from Pacific Biosciences (PacBio) developed in the past decade. The technology enables the long-range sequencing and mapping of DNA molecules, as well as the detection of epigenetic DNA modifications. In the system that was researched, genetic recombination affected genetic modifications and consequently the gene expression of B. fragilis in its entirety. The system can also detect hostile elements such as bacteriophages, and this is the subject of a new research study that is now underway in the laboratory.
The study was supported by the Technion President’s Fund, the Alon Fellowships, The Israel Science Foundation, the Applebaum Family Foundation, the Gutwirth Fellowships, and Human Frontiers.
Click here for the article in Nucleic Acids Research.
Stephen Hawking predicted that a black hole – a celestial object with such strong gravity that nothing can escape its grip – radiates like an ordinary warm object (a “black body,” which emits constant radiation that depends solely on its temperature), like a star. As such, not only should black holes emit radiation, but this “Hawking radiation” from a black hole should be constant over time, like the radiation from a black body. The temperature of the Hawking radiation is determined by the surface gravity. The stronger the force of gravity on the surface of the black hole, the higher the temperature. Though Hawking’s prediction is almost 50 years old, it has not yet been measured in real (celestial) black holes due to the very low Hawking radiation temperature expected, at the nano Kelvin scale or lower.
The group led by Professor Jeff Steinhauer of the Technion Physics Department created a sonic black hole – a system from which sound waves cannot escape, in analogy with real black holes from which not even light can escape beyond a spherical surface termed the event horizon. In a January 4, 2021 paper in Nature Physics, the group showed that stationary Hawking radiation is indeed emitted from a sonic black hole. They measured 97,000 repetitions of the experiment, corresponding to 124 days of continuous measurement, and observed spontaneous Hawking radiation at six different times after the formation of the sonic black hole, and verified that the temperature and strength of the radiation remained constant.
Furthermore, they followed the evolution of Hawking radiation throughout the life of the sonic black hole, and compared and contrasted it with predictions for real black holes. As expected, they first observed the ramp-up of Hawking radiation, which was similar to the ramp-up expected during the formation of a real black hole, followed by the predicted stationary spontaneous emission.
The end of the constant Hawking radiation in the sonic black hole was marked by the formation of an inner horizon, a spherical surface within the sonic black hole, inside of which the sound waves are no longer trapped. This inner horizon radiated outwards and stimulated additional Hawking radiation, resulting in rapid growth of the Hawking radiation beyond the spontaneous emission.
“The experimental results of Professor Steinhauer are of great importance and interest,” said Professor Amos Ori, also of the Technion Physics Department and an expert in the field of general relativity and black holes. “Jeff measures stationary Hawking radiation emitted from a sonic black hole, in agreement with Hawking’s theoretical prediction. This gives very significant experimental support to Hawking’s analysis, which gets experimental approval for the first time in Jeff’s experiments.”
“At the same time,” added Prof. Ori, “the present experiment also showed that after a certain period, the radiation emitted from the system begins to intensify significantly, probably due to the development of stimulated radiation following the formation of the inner horizon. This is a phenomenon that is no longer included in Hawking’s analysis, so it is much more interesting to me. The phenomena observed in this experiment immediately raise the following question: Can real black holes also emit strong stimulated radiation, as Jeff’s sonic black hole did in the experiment? To me, this is a fascinating question and is of critical importance to the physics of black holes as well as astrophysics and cosmology.”
These ground-breaking measurements give the scientific community valuable insights regarding the nature of black holes, sonic and celestial. “Our new long-term goal”, concluded Prof. Steinhauer, “is to see what happens when one goes beyond the approximations used by Hawking, in which the Hawking radiation is quantum, but spacetime is classical. In other words, we would take into account that the analogue black hole is composed of pointlike atoms.”
Six Decades-old Protein-Synthesis Problem Solved at the Technion: After six decades of international effort, Prof. Ashraf Brik’s group at Technion Israel achieves the ultrafast synthesis of a family of peptides and proteins, with huge medical implications
Closing three different rings with selective and fast disulfide bonds formation employing; UV-light, Palladium and Disulfiram
Researchers led by Professor Ashraf Brik of the Schulich Faculty of Chemistry have made an important series of breakthroughs in the synthesis of proteins, which has huge medical implications. The breakthroughs have garnered much attention from the scientific community, and in the span of one week, the group has had five articles accepted for publication in leading scientific journals. All of the publications deal with a novel method of protein synthesis and its implementation in the development of pharmacologically important molecules.
“We anticipate the new synthesis strategies will be a gamechanger in developing new drugs for cancer, intestinal diseases, diabetes, and more,” stated Prof. Brik. Using this novel methodology, his laboratory synthesized plectasin, a peptide that has shown promising antibiotic results against multiresistant bacteria, and linaclotide, a drug used to treat irritable bowel syndrome.
A protein is a chain of amino acids, folded on itself. Forging the chain is a challenge that has already been overcome, but getting it to fold in just the right way has been an ongoing challenge for decades. One element of this challenge is a particular amino acid, cysteine, which forms a disulphide bond with another cysteine along the chain. If there is only one other cysteine on the chain, the bond will be formed, and the protein will fold the way it should. But what if there are more than two cysteines? How can each cysteine be persuaded to attach to the right one, and not to another?
(l-r) Professor Ashraf Brik, Dr. Hao Sun, Ph.D. student Shay Laps, M.Sc. student Fatima Atamleh, laboratory manager Dr. Guy Kamnesky
Until now, scientists had little choice but to allow the proteins to fold, however which way, and filter out the correctly folded ones. Improvements on this basic approach were protein-specific and involved multiple intermediate steps. The process took several hours, or even days, and led to significant loss of material. Prof. Brik’s group was finally able to change that. They were able to find two molecular “cages” that could protect each individual pair of cysteines. One “cage” is unlocked by palladium, and the other by exposure to UV light. When they are unlocked in sequence, only two cysteines are exposed simultaneously, thus only the correct disulphide bond can be formed. Using this method, the team was able to synthesize correctly folded peptides and proteins with up to three disulphide bonds in less than 15 minutes, in one container, and without much material loss.
The researchers who took part in the study were Ph.D. student Shay Laps; M.Sc. student Fatima Atamleh; laboratory manager Dr. Guy Kamnesky; Dr. Hao Sun, who was at the time a postdoctoral fellow in the laboratory and is now a professor at the Nanjing Agriculture University; and primary investigator Prof. Ashraf Brik, who holds the Jordan and Irene Tark Academic Chair at the Schulich Faculty of Chemistry at Technion. He has received multiple awards, the latest of which is the Israel Chemical Society Prize of Excellence in 2019. This study is supported by the European Research Council (ERC) advanced grant.
The COVID-19 pandemic may have created many obstacles, but it also provided opportunities for finding creative ways to overcome them. On January 14th, joint teams of students from the Technion – Israel Institute of Technology and Cornell Tech took part in the final event of a semester-long ideation course, where they presented technological solutions for health challenges.
The course represented the first virtual version of the iTrek program, a yearly effort of the Joan and Irwin Jacobs Technion-Cornell Institute at Cornell Tech that brings New York City-based master’s degree students to Israel to collaborate with Technion students and faculty. While COVID may have kept the Cornell Tech students at home, it did not stop them from visiting Israel virtually and working closely with colleagues in Haifa.
Defi: the winning concept
This year’s iTrek was organized and executed under the leadership of the Jacobs Technion-Cornell Institute, by Co-Directors Michael Escosia, Assistant Director of Operations, and Lucie Milanez, the Project Manager and Program Coordinator at Technion, and the MindState Ideation Lab. Co-founded by Tamar Many (Shenkar College, Tel Aviv University) and Henk van Assen (Yale, Parsons School of Design), MindState explores societal challenges through an interdisciplinary, human-centric methodology to achieve innovative change. The main event, titled Time to Care, was a joint project of MindState Ideation Lab, the Technion, and Cornell Tech, with help and cooperation from the Tel Aviv Sourasky Medical Center.
Academic leadership of the program was provided by Assistant Professor Joachim Behar, Director of the Technion Artificial Intelligence in Medicine Laboratory (AIMLab), Professor Ron Brachman, Director of the Jacobs Institute, and Professor Ariel Orda, the Jacobs Program Head at the Technion. Teaching assistance was provided by Sofia Segal of the Faculty of Biomedical Engineering at Technion.
Twelve multi-disciplinary teams mixed with Technion and Cornell Tech students and professional designers from companies such as Wix, Lightricks, Google, Climacell, and Similar Web took part in the competition through the virtual spaces of Zoom and GatherTown. They, along with mentors from Sourasky Medical Center, tackled problems as varied as communication between patients and staff, challenges of a nurse’s daily routine, early diagnosis of Alzheimer’s disease, and even reducing food waste in hospitals.
The winner Defi aims to develop a portable defibrillator, which runs on a mobile phone’s power supply. They based their project off the fact that access and timely application of a defibrillator can save the life of a person suffering from a heart attack. The team of Ravit Abel (Nanoscience and Nanotechnology M.Sc. Candidate), Alon Gilad (Biomedical Engineering M.Eng. candidate) and Idan Shenfeld (B.Sc. in Computer Engineering, Rothschild program) from the Technion, together with Ashley Dai (Operations Research M.Eng. candidate) and Eric Chan (Double M.Sc. candidate in Applied Information Science and Information Systems) from Cornell Tech proposed a conceptual solution which would eliminate the large battery that constitutes most of the existing defibrillator’s bulk and charge it instead within seconds from any mobile phone. An accompanying app would provide instructions, automatically contact emergency services, and provide caregivers real-time information about the patient’s status. If the groups’ conceptual design would prove feasible, the defibrillator could become compact, cheap, and easy to use.
Second prize went to Minder, aimed at helping the elderly population keep track of medication and stay in touch with physicians as part of their daily routine. Third prize winner, Libi, targets patients recovering post-heart-attack by helping reduce a second incident of cardiac arrest through tracking and education.
By bringing together academics and industry leaders and mixing skills, the Ideation Competition was viewed as “an amazing experience.” Following their victory, Defi team members attributed their success to: “Opportunities to work with top professionals in the field, and to learn about the business side of creating a technological solution concept.” They added that “between us, we all come from different fields; we were able to put together our strengths, come up with different ideas, and achieve together what none of us could have achieved alone.”
Innovation, design thinking, and social impact have always been the driving force of the Jacobs iTrek program. Professor Ronni Gamzu, CEO of Sourasky Medical Center and one of the judges of the competition, concluded the final event by encouraging the teams to “keep on innovating because this is the way to advance medicine, even in the time of an epidemic and pandemic.”
The participating students are either in advanced years of their bachelor’s degrees, or in their graduate degrees. Defi was mentored by Professor Yaron Arbel, director of the Cardiovascular Research Centre at Sourasky Medical Center, and Mr. Eyal Kellner, CIO at the Sourasky Medical Center. The design team assisting them included Elad Rahmin, Oren Elbaz, and Vera Mordehayev from Climacell.
The activity was sponsored by Monday, IMed Medical Habitat, the Technion, the Jacobs Institute at Cornell Tech and the Israel Council for Higher Education. Prize awards in the total amount of $10,000 were provided by the Dr. Joseph Holt and Halaine Maccabee Rose Fund.
The proof-of-concept incorporates real muscle, fat, and vascular-like system similar to a ribeye from a slaughtered cow, in strategy to build a diverse portfolio of cultivated meat cuts of any dimension.
Prof. Shulamit Levenberg with Didier Toubia (right) and graduate student Iris Ianovici (left)
Aleph Farms Ltd. and its research partner at the Faculty of Biomedical Engineering at the Technion – Israel Institute of Technology, have successfully cultivated the world’s first slaughter-free ribeye steak, using three-dimensional (3D) bioprinting technology and natural building blocks of meat – real cow cells, without genetic engineering and immortalization. With this proprietary technology developed just two short years after it unveiled the world’s first cultivated thin-cut steak in 2018 which did not utilize 3D bioprinting, the Company now has the ability to produce any type of steak and plans to expand its portfolio of quality meat products.
Unlike 3D printing technology, Aleph Farms’ 3D bioprinting technology is the printing of actual living cells that are then incubated to grow, differentiate, and interact, in order to acquire the texture and qualities of a real steak. A proprietary system, similar to the vascularization that occurs naturally in tissues, enables the perfusion of nutrients across the thicker tissue and grants the steak with the similar shape and structure of its native form as found in livestock before and during cooking.
“This breakthrough reflects an artistic expression of the scientific expertise of our team,” enthuses Didier Toubia, Co-Founder and CEO of Aleph Farms. “I am blessed to work with some of the greatest people in this industry. We recognize some consumers will crave thicker and fattier cuts of meat. This accomplishment represents our commitment to meeting our consumer’s unique preferences and taste buds, and we will continue to progressively diversify our offerings,” adds Toubia. “Additional meat designs will drive a larger impact in the mid and long term. This milestone for me marks a major leap in fulfilling our vision of leading a global food system transition toward a more sustainable, equitable and secure world.”
The cultivated ribeye steak is a thicker cut than the company’s first product – a thin-cut steak. It incorporates muscle and fat similar to its slaughtered counterpart and boasts the same organoleptic attributes of a delicious tender, juicy ribeye steak you’d buy from the butcher. “With the realization of this milestone, we have broken the barriers to introducing new levels of variety into the cultivated meat cuts we can now produce. As we look into the future of 3D bioprinting, the opportunities are endless,” says Technion Professor Shulamit Levenberg, Aleph’s Co-Founder, Chief Scientific Advisor and a major brainpower behind the company’s IP. Levenberg is considered a global leader in tissue engineering and has amassed over two decades of research in the field at the Massachusetts Institute of Technology (MIT), in the United States and at the Technion, in Israel. Levenberg is also the former Dean of the Biomedical Engineering Faculty at the Technion.
Aleph Farms’ zealous plans to diversify its offering align with its mission to create a global platform for local production, leveraging a highly scalable technology to create culinary experiences that can be adapted for the different food cultures around the world.
About Aleph Farms
Aleph Farms is a food company that is paving a new way forward as a leader of the global sustainable food ecosystem, working passionately to grow delicious beef steaks from non-genetically engineered cells, isolated from a cow, using a fraction of the resources required for raising an entire animal for meat, without antibiotics and without the use of Fetal Bovine Serum (FBS). Aleph Farms was co-founded with The Kitchen Hub of the Strauss Group and with Professor Shulamit Levenberg, former Dean of the Biomedical Engineering faculty of the Technion – Israel Institute of Technology. Aleph Farms is backed by some of the world’s most innovative food producers, such as Cargill, Migros, and the Strauss Group.
The company has recently received top accolades for its contribution to the global sustainability movement from the World Economic Forum, UNESCO, Netexplo Forum, FAO, and EIT Food.
Using AI and computer automation, Technion researchers have developed a “conjecture generator” that creates mathematical conjectures, which are considered to be the starting point for developing mathematical theorems. They have already used it to generate a number of previously unknown formulas. The study, which was published in the journal Nature, was carried out by undergraduates from different faculties under the tutelage of Assistant Professor Ido Kaminer of the Andrew and Erna Viterbi Faculty of Electrical Engineering at the Technion.
The Research Group L-R: Rotem Elimelech, Yoav Harris, Prof. Ido Kaminer and Shahar
The project deals with one of the most fundamental elements of mathematics – mathematical constants. A mathematical constant is a number with a fixed value that emerges naturally from different mathematical calculations and mathematical structures in different fields. Many mathematical constants are of great importance in mathematics, but also in disciplines that are external to mathematics, including biology, physics, and ecology. The golden ratio and Euler’s number are examples of such fundamental constants. Perhaps the most famous constant is pi, which was studied in ancient times in the context of the circumference of a circle. Today, pi appears in numerous formulas in all branches of science, with many math aficionados competing over who can recall more digits after the decimal point: 3.1415926535897932384626433832795028841971693993751058209749445923078164062862089986280348253421170679821480865132823066470938446095505822317253594081284811174502841027019385211055596446229489549303820…
Yahel Manor
The Technion researchers proposed and examined a new idea: The use of computer algorithms to automatically generate mathematical conjectures that appear in the form offormulas for mathematical constants.
A conjecture is a mathematical conclusion or proposition that has not been proved; once the conjecture is proved, it becomes a theorem. Discovery of a mathematical conjecture on fundamental constants is relatively rare, and its source often lies in mathematical genius and exceptional human intuition. Newton, Riemann, Goldbach, Gauss, Euler, and Ramanujan are examples of such genius, and the new approach presented in the paper is named after Srinivasa Ramanujan.
Ramanujan, an Indian mathematician born in 1887, grew up in a poor family, yet managed to arrive in Cambridge at the age of 26 at the initiative of British mathematicians Godfrey Hardy and John Littlewood. Within a few years, he fell ill and returned to India, where he died at the age of 32. During his brief life, he accomplished great achievements in the world of mathematics. One of Ramanujan’s rare capabilities was the intuitive formulation of unproven mathematical formulas. The Technion research team, therefore, decided to name their algorithm “the Ramanujan Machine,” as it generates conjectures without proving them, by “imitating” intuition using AI and considerable computer automation.
Gal Raayoni
According to Prof. Kaminer, “Our results are impressive because the computer doesn’t care if proving the formula is easy or difficult, and doesn’t base the new results on any prior mathematical knowledge, but only on the numbers in mathematical constants. To a large degree, our algorithms work in the same way as Ramanujan himself, who presented results without proof. It’s important to point out that the algorithm itself is incapable of proving the conjectures it found – at this point, the task is left to be resolved by human mathematicians.”
The conjectures generated by the Technion’s Ramanujan Machine have delivered new formulas for well-known mathematical constants such as pi, Euler’s number (e), Apéry’s constant (which is related to the Riemann zeta function), and the Catalan constant. Surprisingly, the algorithms developed by the Technion researchers succeeded not only in creating known formulas for these famous constants, but in discovering several conjectures that were heretofore unknown. The researchers estimate this algorithm will be able to significantly expedite the generation of mathematical conjectures on fundamental constants and help to identify new relationships between these constants.
Yaron Hadad
As mentioned, until now, these conjectures were based on rare genius. This is why in hundreds of years of research, only a few dozens of formulas were found. It took the Technion’s Ramanujan Machine just a few hours to discover all the formulas for pi discovered by Gauss, the “Prince of Mathematics,” during a lifetime of work, along with dozens of new formulas that were unknown to Gauss.
According to the researchers, “Similar ideas can in the future lead to the development of mathematical conjectures in all areas of mathematics, and in this way provide a meaningful tool for mathematical research.”
The research team has launched a website, RamanujanMachine.com, which is intended to inspire the public to be more involved in the advancement of mathematical research by providing algorithmic tools that will be available to mathematicians and the public at large. Even before the article was published, hundreds of students, experts, and amateur mathematicians had signed up to the website.
George Pisha
The research study started out as an undergraduate project in the Rothschild Scholars Technion Program for Excellence with the participation of Gal Raayoni and George Pisha, and continued as part of the research projects conducted in the Andrew and Erna Viterbi Faculty of Electrical Engineering with the participation of Shahar Gottlieb, Yoav Harris, and Doron Haviv. This is also where the most significant breakthrough was made – by an algorithm developed by Shahar Gottlieb – which led to the article’s publication in Nature. Prof. Kaminer adds that the most interesting mathematical discovery made by the Ramanujan Machine’s algorithms to date relates to a new algebraic structure concealed within a Catalan constant. The structure was discovered by high school student Yahel Manor, who participated in the project as part of the Alpha Program for science-oriented youth. Prof. Kaminer added that, “Industry colleagues Uri Mendlovic and Yaron Hadad also participated in the study, and contributed greatly to the mathematical and algorithmic concepts that form the foundation for the Ramanujan Machine. It is important to emphasize that the entire project was executed on a voluntary basis, received no funding, and participants joined the team out of pure scientific curiosity.”
Doron Haviv
Prof. Ido Kaminer is the head of the Robert and Ruth Magid Electron Beam Quantum Dynamics Laboratory. He is a faculty member in the Andrew and Erna Viterbi Faculty of Electrical Engineering and the Solid State Institute. Kaminer is affiliated with the Helen Diller Quantum Center and the Russell Berrie Nanotechnology Institute.
Dynamic, Sophisticated, and Environmentally Sensitive: How mRNA Formulates Its Instructions to Ribosomes
Technion researchers have discovered a new mechanism in the control of protein synthesis by ribosomes: an enzyme that edits mRNA and regulates its activity according to the organism’s needs. Their recent article describes similar gene editing processes to those used by Pfizer and Moderna in developing the new mRNA vaccines
In the diagram: Left: The vaccines. mRNA vaccines are based on the introduction of synthetic mRNA into cells to serve as a mold for building the viral protein that activates the immune system. Shortly after the mRNA molecules have penetrated the cell they begin to initiate production of the immunological proteins the cell needs. mRNA contains a number of chemical modifications that enhance its activity in the cell. Right: The natural mechanism. The study published in Nucleic Acids Research demonstrates how similar chemical modifications occurring naturally in mRNA serve as links to control elements. These links affect ribosome activity, thus enabling protein production in quantities that are more accurate and are aligned with the organism’s needs.
Technion researchers have discovered an unknown mechanism that controls protein synthesis in the cell. The mechanism uses chemical modifications on mRNA to influence the rate of protein production by the ribosome, the cellular protein machine. The researchers, Professor Yoav Arava and doctoral student Ofri Levi of the Faculty of Biology, published news of the discovery in Nucleic Acids Research.
Gene expression control is responsible for translating the genetic code (written in DNA) into proteins that are adapted for their purpose in the specific tissue, taking changing environmental conditions into account. “If DNA is the cookbook,” said Ofri Levi, “then the chef is the ribosome – the cellular protein machine. The main mediator in the process is the mRNA molecule, which carries the recipe from the DNA to the ribosome. The right interaction between mRNA and the ribosome is vital to the normalcy and quality of the proteins.”
Prof. Yoav Arava
For some years, it has been known that mRNA does not carry the instructions from DNA in their original form, but undergoes numerous modifications on the way. These chemical changes recently made headlines in the context of the COVID-19 vaccines; the Pfizer and Moderna vaccines are based on the introduction of synthetic mRNA into the body to create immunological proteins inside our cells. However, since the cell treats mRNA as a foreign body, it tends to attack it, and the rapid mRNA breakdown does not leave it with enough time to manufacture the essential proteins.
To overcome this challenge, the two companies integrated modifications that mimic natural changes that occur in the body into their mRNA molecules. These modifications indeed enable the synthetic molecule to survive and to work long enough to create the protein from the virus.
According to Prof. Arava, “The connection between mRNA and the production of proteins is a process that has occupied us for some years, and we are focusing on the effect of mRNA on building the proteins and on their stability. We are trying to understand the ‘conversation’ in which mRNA tells the ribosome what to manufacture for the cell. We are conducting the basic research on Saccharomyces cerevisiae, a budding yeast that we know as baking or brewing yeast, and we have a solid basis to assume that what happens in the yeast is highly relevant to what happens in the human body.”
In a previous article published in PLoS Biologyin July 2019, Mr. Levi and Prof. Arava presented a new role for certain enzymes prevalent in all kingdoms of life. The researchers discovered that these enzymes serve as significant control elements in protein production – a role that was unknown before the article was published. To perform this function, these enzymes bind to the mRNA and regulate the quantity of mRNA molecules available to the ribosome.
In the present study, Mr. Levi and Prof. Arava thoroughly explored the question as to how those enzymes identify mRNA among the medley of cellular components. They discovered that the answer lies in a unique chemical modification occurring in mRNA. This modification, known as pseudouridine, is created in various locations on mRNA; control elements identify the change and time ribosome activity accordingly.
To prove the importance of this modification, the researchers developed a method based on CRISPR/Cas9, which enabled them to “surgically” remove the psuedouridine without causing any other damage to the cells. Indeed, in the absence of psuedouridine, control of protein production was lost. According to Mr. Levi, “Like many scientists in the world, we too owe a huge thank you to Professor Emmanuelle Charpentier and Professor Jennifer Doudna for the dramatic breakthrough they achieved in the development of the CRISPR/Cas9 technology.”
Profs. Charpentier and Doudna were awarded the Technion Harvey Prize on November 3, 2019, and one year later, on December 10, 2020, they received the Nobel Prize in Chemistry for the development of the revolutionary technology for editing, repairing, and rewriting DNA. Thanks to this technology, Mr. Levi said, “we have been able to make progress in our research with unprecedented speed and accuracy.”
The Technion researchers estimate this is an evolutionarily conserved mechanism that exists across the animal kingdom. Since the mechanism is sensitive to environmental changes, it provides mRNA molecules with instructions tailored to environmental conditions, thus directing the ribosomes to optimal protein production.
As mentioned, one of the most important tasks faced by Pfizer and Moderna was to improve the activity of artificial mRNA in the human body, so they introduced a modification to the “immunological” mRNA that is very similar to pseudouridine. “We don’t yet know if the control elements we discovered are also able to detect the modification in synthetic mRNA,” said Prof. Arava. “If they are, this may open up further possibilities to improve mRNA activity and produce larger quantities of proteins.”
Beyond the present research and its implications, said Prof. Arava, “our discovery illustrates the importance of basic research in the development of sophisticated medical treatments and innovative vaccines. The public and the media are mainly hungry for publications about developments and applied science, but without a strong, broad infrastructure of basic science – in directions in which the applied horizon is not always clear – we would not witness such dramatic breakthroughs in diagnosis, treatment, and vaccines, as well as in areas of life outside the world of medicine.”
The research was funded by the Israel Science Foundation (ISF). Ofri Levi is the winner of the Jacobs Scholarship for Outstanding Students.
Click herefor the complete article in Nucleic Acids Research.
Revolutionary Neu-ChiP project will see scientists use human brain stem cells on microchips to push the boundaries of artificial intelligence (AI)
Scientists have started work on a project that will see human brain stem cells used to power artificial intelligence (AI) devices and bring about a revolution in computing.
The Neu-ChiP project, an international collaboration led by researchers at Aston University, has been awarded €3.5m (£3.06m) to show how neurons – the brain’s information processors – can be harnessed to supercharge computers’ ability to learn while dramatically cutting energy use.
SEM image of a primary rat neuronal culture grown on the 3D CMOS-MEA. Neurons are located on top and at the base of the structured electrodes CREDIT: 3Brain AG
The research team is now embarking on a three-year study to demonstrate how human brain stem cells grown on a microchip can be taught to solve problems from data, laying the foundations for a “paradigm shift” in machine learning technology.
The use of AI is becoming ever more prevalent in areas as diverse as healthcare, finance, autonomous vehicles, and speech recognition, right through to recommending films through on-demand services like Netflix. The ‘big four’ tech companies – Apple, Google, Amazon, and Facebook – and many others are investing heavily in machine learning to tailor their products and better understand their customers.
But current electronic approaches to machine learning have limits, requiring ever-growing computing power and high energy demands. The recent trend towards ‘neuromorphic computing’, which aims to mimic human neural activity electronically, is hampered by the inherent limitations of conventional electronics.
In contrast, human brain cells effortlessly combine these functions and have extremely low power demands, requiring only a small volume of a nutrient-rich solution to operate.
In the Neu-ChiP project, the team will layer networks of stem cells resembling the human cortex onto microchips. They will then stimulate the cells by firing changing patterns of light beams at them. Sophisticated 3D computer modeling will allow them to observe any changes the cells undergo, to see how adaptable they are. This imitates the ‘plasticity’ of the human brain, which can rapidly adapt to new information.
The project, funded by the European Commission’s Future and Emerging Technologies (FET) program and involving partner institutions in the UK, France, Spain, Switzerland, and Israel, is also expected to produce new knowledge about the functioning of the brain which could be used to develop novel stem cell-based treatments.
Professor David Saad, Professor of Mathematics at Aston University, said: “Our aim is to harness the unrivaled computing power of the human brain to dramatically increase the ability of computers to help us solve complex problems. We believe this project has the potential to break through current limitations of processing power and energy consumption to bring about a paradigm shift in machine learning technology.”
Dr. Rhein Parri, Reader in Pharmacology at Aston University, said: “We are very excited to have won support from the European Commission for this ambitious project. Our international team will combine their expertise and work together to develop technology that we expect to provide great future benefits for science and society.”
Dr. Eric Hill, Senior Lecturer in Stem cell Biology at Aston University, said: “Our ability to turn human stem cells into brain cells has revolutionized the study of the human brain. This exciting interdisciplinary project will bring international scientists from diverse backgrounds together to develop new technologies that will provide huge insight into the development of human neuronal networks”.
The project involves academic partners from Loughborough University (UK), the University of Barcelona (Spain), Centre National de la Recherche Scientifique (CNRS, France), Technion Israel Institute of Technology (Israel), and the company 3Brain AG (Switzerland).
Drs Jordi Soriano, Associate Professor in Physics, and Daniel Tornero, Tenure Track Professor in Biology, both at the University of Barcelona, said: “Our ability to engineer neuronal circuits in a dish and train them to conduct data analysis will provide new insights on how the brain computes information and finds solutions. The developed technology may even help to design unique and exciting human-machine interfaces.”
Professor Rémi Monasson, Director of Research at the Centre National de la Recherche Scientifique (CNRS), said: “In Neu-ChiP, we will not only model a system made of many extraordinarily complex components – human neural cells – but we will try to go far beyond. Our aim is to drive the neural system to a state in which it will be able to carry out nontrivial computations.”
Drs Shahar Kvatinsky, Associate Professor of Electrical Engineering, and Daniel Ramez, Assistant Professor of Biomedical Engineering, both at Technion Israel, said: “We are seeking to build neuromorphic circuits and combine emerging electronic devices with biological neurons and this project is a major step towards this target. In the context of synthetic biology, it is impressive to see how computation in living cells is evolving from digital through analog and moving towards a neuromorphic computing paradigm.”
Dr. Alessandro Maccione, co-founder and Chief Scientific Officer of 3Brain AG, said: “The Neu-ChiP project has the ambitious plan to overcome current machine learning approaches through the study of complex human-brain-based circuits. We are proud to put our technology at the service of this pioneering and exciting challenge.”
Dr. Paul Roach, Senior Lecturer in Biomaterials and Interface Science at Loughborough University, said: “This work really brings together an exciting interdisciplinary team of researchers to build on our individual strengths and interests. The focus of this project is on revolutionizing the way we analyze information using specifically designed complex living neuronal circuits.”
