Researchers trace continuity in Israel's local wine industry from the Byzantine period to the present day


Research
Researchers trace continuity in Israel's local wine industry from the Byzantine period to the present day

A new study led by the paleogenetic laboratory of the Steinhardt Museum of Natural History at Tel Aviv University and the University of Haifa analyzed DNA from ancient local winegrape seeds discovered at archaeological excavations in the Negev. One seed was found to be almost identical to the Syriki variety used today to make high-quality red wine in Greece and Lebanon, while another seed is a relative of the white variety called Be'er, still growing in deserted vineyards in the dunes of Palmachim.
The genetic study was led by Dr. Pnina Cohen and Dr. Meirav Meiri of the paleogenetic lab at the Steinhardt Museum of Natural History at Tel Aviv University. The seeds were found at archaeological excavations led by Prof. Guy Bar-Oz from the School of Archaeology and Maritime Cultures at the University of Haifa, in collaboration with researchers from the Israel Antiquities Authority. Other participants included researchers from the University of Haifa, the Weizmann Institute, Bar-Ilan University, and research institutions in France, Denmark, and the UK. The paper was published in the leading scientific journal PNAS.
"The findings include large winepresses, jugs in which the exclusive wine, exported to Europe, was stored, and grape seeds preserved for more than a thousand years. This industry gradually declined following the Muslim conquest in the 7th century, since Islam forbids the consumption of wine." - Prof. Guy Bar-Oz
"Archaeological excavations conducted in the Negev [in Israel] in recent years have revealed a flourishing wine industry from the Byzantine and early Arab periods (around the fourth to ninth centuries A.D.), especially at the sites of Shivta, Haluza, Avdat, and Nizana, which were large, thriving cities at the time," says Prof. Guy Bar-Oz from the University of Haifa.
"The findings include large winepresses, jugs in which the exclusive wine, exported to Europe, was stored, and grape seeds preserved for more than a thousand years. This industry gradually declined following the Muslim conquest in the 7th century, since Islam forbids the consumption of wine."
"The cultivation of winegrapes in the Negev was renewed only in modern times, in the state of Israel, mostly since the 1980s. This industry, however, relies mainly on winegrape varieties imported from Europe."

Avdat Excavation (photo: Tali. Erickson-Gini and Scott Bucking)
Extracting DNA
One especially interesting finding was a large hoard of grape seeds, discovered on the floor of a sealed room at Avdat. The researchers explain that these seeds have been relatively well preserved thanks to protection from climatic phenomena such as extreme temperatures, flooding, or dehydration. To learn more about the seeds, in the hope of discovering which varieties they might belong to, the researchers prepared to extract their DNA in the paleogenetic lab.
"The science of paleogenomic uses a range of advanced technologies to analyze ancient genomes, primarily from archaeological findings," explains Dr. Meiri from the Steinhardt Museum of Natural History at Tel Aviv University. "Since the DNA molecule is very sensitive and disintegrates over time, especially under high temperatures, we usually get only small pieces of DNA, often in a poor state of preservation. To protect them we work under special conditions: the paleogenetic lab is an isolated clean laboratory, with positive air pressure that keeps contaminants out, and we enter it in sterilized 'spacesuits' familiar to everyone from the COVID pandemic."
To begin with, the researchers looked for any organic matter remaining in the seeds. For this purpose, they used FTIR (Fourier-transform infrared spectroscopy) – a chemical technique applying infrared radiation to produce a light spectrum that identifies the sample's content. Finding remnants of organic matter in 16 seeds, the researchers went on to extract DNA from these samples.

Ancient local winegrape seeds from Shivta, Israel (photo: Prof. Guy Bar-Oz, The University of Haifa)
The extracted DNA was sequenced, with an emphasis on about 10,000 genomic sites where variety-specific features are usually found, and the results were compared to databases of modern grapevines from around the world: In 11 samples, the quality of genetic material was too poor to allow any definite conclusions. Three of the remaining samples were identified as generally belonging to local varieties. Finally, the two samples of the highest quality, both from around 900 A.D., were identified as belonging to specific local varieties that still exist today.
The discovery was quite extraordinary:
"The wonderful thing about paleogenetics is that sometimes, tiny items can tell a big story. This is exactly what happened in this study. With just a bit of DNA extracted from two grape seeds we were able to trace continuity in the local wine industry - from the Byzantine period, more than a thousand years ago, to the present day." - Dr. Meirav Meiri
"The wonderful thing about paleogenetics is that sometimes, tiny items can tell a big story," says Dr. Meiri. "This is exactly what happened in this study. With just a bit of DNA extracted from two grape seeds we were able to trace continuity in the local wine industry - from the Byzantine period, more than a thousand years ago, to the present day."
"We believe that our findings are also significant for Israel's modern wine industry, which has been growing and thriving in recent decades. Today, most varieties grown here have been imported from Europe, so that the local conditions are not optimal for them. Local varieties can be more suitable for the local climate and soil, especially in the desert region of the Negev. Our study opens new paths for restoring and improving ancient local varieties, to create winegrapes that are more suitable for challenging climatic conditions such as high temperatures and little rainfall."

Tiny items can tell a big story. Ancient winegrape seeds under a Microscope from Avdat (photo: Prof. Guy Bar-Oz, The University of Haifa)

Research
Using RNA-based nanodrugs the researchers achieve 80% survival rate in lab models

Ovarian cancer ranks fifth in cancer deaths among women, accounting for more deaths than any other cancer of the female reproductive system. In a study conducted at Tel Aviv University researchers used protein CKAP5 (cytoskeleton-associated protein) for the first time as a therapeutic target for RNA-based nanodrugs. After identifying a genetically unstable mutation resistant to both chemotherapy and immunotherapy in the tissues of ovarian cancer, the researchers targeted these cells with lipid nanoparticles containing RNA for silencing CKAP5 - causing the cells to collapse and achieving an 80% survival rate in animal models.
"The lipid nanoparticles developed by Prof. Peer enabled us for the first time to silence [the CKAP5] protein through targeted delivery of an RNA drug. We proved that CKAP5, a protein responsible for the cell's stability, can be silenced, and that this procedure collapses and destroys the entire cancer cell." - Dr. Sushmita Chatterjee
The breakthrough was achieved by a TAU research team led by Prof. Dan Peer of The Shmunis School of Biomedicine and Cancer Research, a global pioneer in the development of RNA-based drugs, Head of the Laboratory of Precision Nanomedicine, and TAU's VP for R&D; and by Dr. Sushmita Chatterjee, post-doctoral student from India at Prof. Peer’s lab, in collaboration with Prof. David Sprinzak of The George S. Wise Faculty of Life Sciences and Prof. Ronen Zaidel-Bar of the Sackler Faculty of Medicine. The study was funded by the Rivkin Foundation for Ovarian Cancer Research and the Shmunis Family Foundation. The results were published in the leading scientific journal Science Advances.
"The protein CKAP5 has never been studied with relation to the fight against cancer, simply because there was no known way to silence it," explains Dr. Chatterjee. "The lipid nanoparticles developed by Prof. Peer enabled us for the first time to silence this protein through targeted delivery of an RNA drug. We proved that CKAP5, a protein responsible for the cell's stability, can be silenced, and that this procedure collapses and destroys the entire cancer cell."

Prof. Dan Peer
At the second stage of the study the researchers tested the new CKAP5-silencing RNA drug on 20 types of cancer. Some cancer cells proved more sensitive than others to this procedure. Cancers displaying high genetic instability, which are usually highly resistant to chemotherapy, were found to be especially sensitive to the silencing of CKAP5.
"As researchers, we are involved in something like a dominoes game: we always look for the one piece in the cancer's structure that is so important, that if we pull it out the entire cell will collapse. CKAP5 is such a domino piece, and we are already working on more applications (…)" - Prof. Dan Peer
"All cancer cells are genetically unstable," says Dr. Chatterjee. "Otherwise, they would be healthy, not cancerous. However, there are different levels of genetic instability. We found that cancer cells that are more unstable, are also more affected by damage to CKAP5. Our drug pushed them to their limit, and essentially destroyed their structure. Our idea was to turn the trait of genetic instability into a threat for these cells, by using RNA to silence the flawed protein. We demonstrated for the first time that CKAP5 can be used to kill cancer cells, and then observed the biological mechanism that causes the cancer cells to collapse in the protein's absence."
Equipped with these insights, the researchers tested the new drug in an animal model for ovarian cancer, achieving a survival rate of 80%.
"We chose ovarian cancer because it's a good target," explains Prof. Peer. "While highly resistant to both chemotherapy and immunotherapy, this type of cancer is very sensitive to the silencing of CKAP5. It should be emphasized that the CKAP5 protein is a new target in the fight against cancer. Targeting cell division is not new, but using RNA to target proteins that make up the cell's skeleton (cytoskeleton) – this is a new approach and a new target that must be further investigated. As researchers, we are involved in something like a dominoes game: we always look for the one piece in the cancer's structure that is so important, that if we pull it out the entire cell will collapse. CKAP5 is such a domino piece, and we are already working on more applications, this time in blood cancers."