After developing an innovative technology that enables the growth of seaweed enriched with proteins and minerals such as zinc, iron, iodine, magnesium, and calcium for humans and animals, researchers from Tel Aviv University’s School of Zoology at The George S. Wise Faculty of Life Sciences and the Israel Oceanographic and Limnological Research Institute (IOLR) have made a new advancement: They succeeded in significantly increasing the ability of seaweed to produce healthy natural substances, focusing on enhancing the production of bio-active compounds that offer medical benefits to humans, such as antioxidants – the concentration of which was doubled in the seaweed; natural sunscreens – its concentration tripled; and unique protective pigments of great medical value, the concentration of which increased by ten-fold.

The study was carried out with the innovative and sustainable approach of integrated aquaculture, which combines seaweed with fish cultivation, upgrading the seaweed while at the same time helping to purify the seawater and minimizing negative environmental impacts. According to the researchers, these findings may serve the pharmaceutical, cosmetics, food, and nutritional supplement industries.  

Manufacturers of Valuable Compounds

The new development was led by Ph.D. student Doron Ashkenazi of Tel Aviv University and the Israel Oceanographic and Limnological Research Institute, under the guidance of Prof. Avigdor Abelson of Tel Aviv University’s School of Zoology and Prof. Alvaro Israel of the IOLR in Haifa, in collaboration with other leading researchers from Israel and around the world, including Guy Paz from IOLR; organic chemistry expert Dr. Shoshana Ben-Valid; Dr. Eitan Salomon from the National Center for Mariculture in Eilat; and Prof. Félix López Figueroa, Julia Vega, Nathalie Korbee, and Marta García-Sánchez from Malaga University in Spain. The article was published in the scientific journal Marine Drugs.

Ph.D. student Doron Ashkenazi (left) and Prof. Avigdor Abelson (right)

Doron Ashkenazi explains that “seaweed, also known as macroalgae, are marine plants that form the basis of the coastal marine ecosystem. The seaweed absorb carbon dioxide and release oxygen into the environment. They purify the water, provide food, habitat, and shelter for numerous species of fish and invertebrates. Not many know that seaweed also produce a wide variety of distinct bio-active compounds that are beneficial to humans. The seaweed living in the intertidal zone face extreme stress conditions, which include changes in salinity, temperature, desiccation [loss of moisture] conditions, changes in the availability of nutrients and high exposure to solar radiation, especially in the ultraviolet (UV) range.”

“Not many know that seaweed also produce a wide variety of distinct bio-active compounds that are beneficial to humans.” Doron Ashkenazi

To survive, the seaweed has developed a unique set of chemical defense mechanisms – natural chemicals that help them cope with these harsh environments. They are highly efficient natural factories that produce valuable substances that may offer significant benefits to humans.

In the current study, they sought to examine whether and how it is possible to increase and maximize the seaweed’ production of bio-active compounds, and secondary metabolites, that offer significant health benefits. These substances include antioxidants, protective pigments, and natural UV radiation filters.

A dedicated aquaculture system where the researchers grew three local species of algae

Future Looking Greener Than Ever?

To this end, the researchers developed an original and practical cultivation approach, whereby three local seaweed – Ulva, Gracilaria and Hypnea – were initially grown alongside fish effluents, and subsequently exposed to stressors including high irradiance, nutrient starvation, and high salt content.

They investigated how these changes affected the concentration of specific valuable biomaterials in the seaweed, to enhance their production. The results were impressive: antioxidant levels had doubled, seaweed natural sunscreen molecules tripled, and protective pigments were increased by ten-fold. “We developed optimal cultivation conditions and invented a new and clean way to increase the levels of healthy natural bio-active compounds in seaweed to an unprecedented level,” says Ashkenazi. “We in fact produced ‘super seaweed’ tailor designed to be utilized by the emerging health industries for food and health applications.”

“In the future, humanity will focus on creating science-based environmental solutions (…) technologies that promote recycling and the sound use of natural resources without overexploiting them.” Doron Ashkenazi  

The researchers believe that in the future it will be possible to use their cultivation approach to elevate in seaweed additional natural materials with important medical properties, such as anti-cancer, anti-diabetic, anti-inflammatory, anti-viral, and ant-biotic substances.

They also emphasize that seaweed aquaculture is environmentally friendly, preserving the ecological balance, and reducing environmental risks by minimizing excessive amounts of pollutants caused by humans, reducing the emission of greenhouse gases, and lowering the carbon footprint. In this way, seaweed aquaculture can help cope with global environmental challenges such as pollution, habitat loss, and the climate crisis.

“In the future, humanity will focus on creating science-based environmental solutions, like the one we offer in this study – technologies that promote recycling and the sound use of natural resources without overexploiting them. Our study demonstrates how we can enjoy nature without harming it,” concludes Ashkenazi.

For the first time worldwide, a team of researchers from Tel Aviv University and the Israel Institute for Biological Research have developed an mRNA-based vaccine that is 100% effective against a type of bacteria that is lethal to humans. The study, conducted in a lab model, demonstrated that all treated models were fully protected against the bacteria. The researchers believe their new technology can enable rapid development of effective vaccines for bacterial diseases, including diseases caused by antibiotic-resistant bacteria, for example in case of a new fast-spreading pandemic.

“In our study we proved that it is, in fact, possible to develop mRNA vaccines that are 100% effective against deadly bacteria.” Dr. Edo Kon

Quickly Developed

The study was led by Tel Aviv University’s Dr. Edo Kon and Prof. Dan Peer, VP for R&D and Head of the Laboratory of Precision Nano-Medicine at The Shmunis School of Biomedicine and Cancer Research at The George S. Wise Faculty of Life Sciences, in collaboration with researchers from the Israel Institute for Biological Research: Dr. Yinon Levy, Uri Elia, Dr. Emanuelle Mamroud, and Dr. Ofer Cohen. The results of the study were published in the journal Science Advances.

“So far, mRNA vaccines, such as the COVID-19 vaccines which are familiar to all of us, were assumed to be effective against viruses but not against bacteria,” explains Dr. Edo Kon. “The great advantage of these vaccines, in addition to their effectiveness, is the ability to develop them very quickly: once the genetic sequence of the virus SARS-CoV2 (COVID-19) was published, it took only 63 days to begin the first clinical trial. However, until now scientists believed that mRNA vaccines against bacteria were biologically unattainable. In our study we proved that it is, in fact, possible to develop mRNA vaccines that are 100% effective against deadly bacteria.”

Running RNA gel

Combining Breakthrough Strategies

The researchers explain that viruses depend on external (host) cells for their reproduction. Inserting its own mRNA molecule into a human cell, a virus uses our cells as a factory for producing viral proteins based on its own genetic material, namely replicates of itself.

In mRNA vaccines this same molecule is synthesized in a lab, then wrapped in lipid nanoparticles resembling the membrane of human cells. When the vaccine is injected into our body, the lipids stick to our cells, and consequently the cells produce viral proteins. The immune system, becoming familiar with these proteins, learns how to protect our body in the event of exposure to the real virus.

Since viruses produce their proteins inside our cells, the proteins translated from the viral genetic sequence resemble those translated from the lab-synthesized mRNA.

“If tomorrow we face some kind of bacterial pandemic, our study will provide a pathway for quickly developing safe and effective mRNA vaccines.” Prof. Dan Peer

Bacteria, however, are a whole different story: They don’t need our cells to produce their own proteins. And since the evolutions of humans and bacteria are quite different from one another, proteins produced in bacteria can be different from those produced in human cells, even when based on the same genetic sequence.

“Researchers have tried to synthesize bacterial proteins in human cells, but exposure to these proteins resulted in low antibodies and a general lack of protective immune effect, in our bodies,” explains Dr. Kon. “This is because, even though the proteins produced in the bacteria are essentially identical to those synthesized in the lab, being based on the same ‘manufacturing instructions’, those produced in human cells undergo significant changes, like the addition of sugars, when secreted from the human cell.”

“To address this problem, we developed methods to secrete the bacterial proteins while bypassing the classical secretion pathways, which are problematic for this application. The result was a significant immune response, with the immune system identifying the proteins in the vaccine as immunogenic bacterial proteins. To enhance the bacterial protein’s stability and make sure that it does not disintegrate too quickly inside the body, we buttressed it with a section of human protein. By combining the two breakthrough strategies we obtained a full immune response.”

WATCH: Prof. Dan Peer and Dr. Edo Kon on the world’s first mRNA vaccine for deadly bacteria

Solution to Antibiotic-resistant Bacteria?

“There are many pathogenic bacteria for which we have no vaccines,” adds Prof. Peer. “Moreover, due to excessive use of antibiotics over the last few decades, many bacteria have developed resistance to antibiotics, reducing the effectiveness of these important drugs. Consequently, antibiotic-resistant bacteria already pose a real threat to human health worldwide. Developing a new type of vaccine may provide an answer to this global problem.”

“In our study, we tested our novel mRNA vaccine in animals infected with a deadly bacterium. Within a week, all unvaccinated animals died, while those vaccinated with our vaccine remained alive and well. Moreover, in one of our vaccination methods, one dose provided full protection just two weeks after it was administered. The ability to provide full protection with just one dose is crucial for protection against future outbreaks of fast-spreading bacterial pandemics. It is important to note that the COVID-19 vaccine was developed so quickly because it relied on years of research on mRNA vaccines for similar viruses. If tomorrow we face some kind of bacterial pandemic, our study will provide a pathway for quickly developing safe and effective mRNA vaccines.”

The study was funded by research grants from the European Union (ERC; EXPERT) and the Shmunis Family (for Prof. Peer).

A new model developed at Tel Aviv University offers a possible solution to the scientific question of why neutral sequences, sometimes referred to as “junk DNA”, are not eliminated from the genome of living creatures in nature and continue to exist within it even millions of years later.

According to the researchers, the explanation is that junk DNA is often located in the vicinity of functional DNA. Deletion events around the borders between junk and functional DNA are likely to damage the functional regions and so evolution rejects them. The model contributes to the understanding of the huge variety of genome sizes observed in nature.

Border Induced Selection

The model describes a phenomenon which the team of researchers refer to as “border induced selection,” and was developed under the leadership of PhD student Gil Loewenthal in the laboratory of Prof. Tal Pupko from the Shmunis School of Biomedicine and Cancer Research at the The George S. Wise Faculty of Life Sciences and in collaboration with Prof. Itay Mayrose, also from TAU’s Faculty of Life Sciences. The study was published in the journal Open Biology.

Throughout evolution, the size of the genome in living creatures in nature changes. For example, some salamander species have a genome ten times larger than the human genome. “The rate of deletions and short insertions, dubbed ‘indels’, is usually measured by examining pseudogenes,” explains Prof. Pupko. “Pseudogenes are genes that have lost their function, and in which there are frequent mutations, including deletions and insertions of DNA segments.”

In previous studies that characterized the indels, it was found that the rate of deletions is greater than the rate of additions in a variety of creatures including bacteria, insects, and even mammals such as humans.

Prof. Tal Pupko

Reverse Bias for Short Segments

The question the researchers sought to answer is how the genomes are not deleted when the probability of DNA deletion events is significantly greater than DNA addition events: “We have provided a different view to the dynamics of evolution at the DNA level,” says Loewenthal. “When measuring the rate of indels there will be more deletions, but the measurements are carried out in pseudogenes which are quite long sequences. We assert that in shorter neutral segments, deletions would likely remove adjacent functional segments which are essential for the functioning of the organism, and they will therefore be rejected [through ‘border-induced selection’]. Accordingly, we assert that when the segment is short, there will be a reverse bias – there will be more insertions than deletions – and therefore short neutral segments are usually retained.”

“In our study, we simulated the dynamics of indels, while taking into account the effect of ‘border-induced selection,’ and compared the simulation results to the distribution of human intron lengths (introns are DNA segments in the middle of a protein-coding gene, which themselves do not code for a protein). A good match was obtained between the results of the simulations and the distribution of lengths observed in nature, and we were able to explain peculiar phenomena in the length distribution of introns, such as the large variation in intron lengths, as well as the complex shape of the distribution which does not look like a standard bell curve.”

An extensive international study identified a new family of snakes: Micrelapidae. According to the researchers, Micrelaps, small snakes usually with black and yellow rings, diverged from the rest of the evolutionary tree of snakes about 50 million years ago. As far as they know, the new family includes only three species, one in Israel and neighboring countries, and two in East Africa.

“Today we tend to assume that most large groups of animals, such as families, are already known to science, but sometimes we still encounter surprises, and this is what happened with Micrelapid snakes.” Prof. Shai Meiri

Exploring the Micrelaps’ Family Tree

The study was conducted by Prof. Shai Meiri of TAU’s School of Zoology, The George S. Wise Faculty of Life Sciences, and of The Steinhardt Museum of Natural History Museum, as well as researchers from Finland, the USA, Belgium, Madagascar, Hong Kong, and Israel. The paper was published in Molecular Phylogenetics and Evolution.

“Today we tend to assume that most large groups of animals, such as families, are already known to science, but sometimes we still encounter surprises, and this is what happened with Micrelapid snakes,” explains Prof Meiri.

“For years, they were considered members of the largest snake family, the Colubridae, but multiple DNA tests conducted over the last decade contradicted this classification. Since then, snake researchers around the world have tried to discover which family these snakes belong to – to no avail. In this study we joined the scientific effort.”

The researchers used micro-CT technology – high-resolution magnetic imaging, to examine the snake’s morphology, focusing specifically on the skull. In addition, they applied methods of deep genomic sequencing – examining about 4,500 ultra-conserved elements, namely regions in the genome that take millions of years to exhibit any change.

Prof. Meiri explains that “in addition to the DNA of Micrelaps, we sampled DNA from various snake groups to which they might have belonged. This way, we discovered some unique genomic elements in Micrelaps, which were not found in any of the other groups.”

Prof. Shai Meiri

“Even through these snakes have been known for decades, they were mistakenly included in other families for many years.” Prof. Shai Meiri

Family Relocation

According to the researchers their findings indicate that Micrelaps diverged from the rest of the evolutionary tree of snakes about 50 million years ago. Since then, these snakes have evolved independently, as a distinct and separate family.

Apparently, this is a very small family, including only three species: two in Kenya and Tanzania in East Africa, and one in Israel and nearby regions (northern Jordan and the Palestinian Authority, southern Syria, and southern Lebanon). The geographic dispersion suggests that these snakes probably originated in Africa, and then, at some point in their history, some of them made their way north through the Great Rift Valley.

“In this study we were able to associate a new snake family – the Micrelapidae. Even through these snakes have been known for decades, they were mistakenly included in other families for many years. Since most animals have already been classified into well-defined families, such a discovery of a new family is quite a rare occurrence in modern science,” concludes Prof. Meiri.   

Featured image: Small with black and yellow rings, some 50 million years old. Meet the Micrelaps snake (photo: Alex Sablenco )