Dr Shahar Alon has developed a unique technology for profiling RNA molecules in tissue

Show me your neighbors and I’ll tell you who you are

Dr. Shahar Alon, a new faculty member, talks about the unique technology he developed at MIT, which lets researchers identify the exact location of RNA molecules inside tissue – highly valuable information in fields such as learning and memory, Alzheimer’s prevention and cancer research.

DNA, the molecule that carries the genetic information necessary for structuring cell proteins, is one of the most well-known and researched subjects in biology. A lesser known but no less important one is the RNA, a mediator between the DNA and the proteins. It can provide copious amounts of information, such as what portions of the information stored in the DNA will become proteins. “However,” says Dr. Shahar Alon, “when it comes to brain tissue, RNA is more than just a messenger. If it was, it would have been an exact copy of the DNA: if DNA is a book, then RNA is a copy of a certain page. We were able to show that in brains of squids and octopuses, known to be highly advanced creatures, RNA copies are not completely identical to the DNA; they are a variation. Textbooks describe RNA as a classic music performer: it has the sheet music and plays accordingly. When it comes to squids and octopuses, the RNA is a jazz player; it has the sheet music, but improvises.”

Dr. Alon (40) has been researching RNA since his PhD studies. After graduating early with a BSc in physics from Bar Ilan University, and working for several years in his field in the Ministry of Defense, he attended Tel Aviv University where he attained his MA and PhD at the Program for Neuroscience, as part of the physics and biology departments. He dedicated his PhD research to RNA, analyzing biological big data and using it to research the complexity of biological systems. “comparing between the RNA in the tissue of a healthy person and that of a sick person can teach us a lot about the disease,” says Alon. “During my research, I developed computational tools to better measure RNA molecules, both in human brain tissue and in many other animals.”

After completing his PhD, Alon attended MIT as a postdoctoral fellow under the supervision of Prof. Ed Boyden, who specializes in brain research technology. During their five years of working together, Boyden and Alon developed a new technology for high throughput RNA measurement inside tissues. “Previous technologies included dissolving the tissue and extracting the molecules for measurement, which prevented us from knowing what was the exact position of the molecule in the tissue. Our technology allows measuring millions of RNA molecules within the tissue with nanoscale precision, without extracting them. Since it is important to know the location of molecules within complex tissue, this technology is of great significance to tissue research in general,” says Alon.

Alon’s technology is of particular importance to two fields of research. The first is the study of brain tissue: “the molecules’ location in the tissue affects processes such as learning and memory. For the first time, our technology allows measuring the location of the different RNA molecules inside intact brain tissue with the resolution of individual synapses. We can find out which of the molecules takes part in the processes of memory and learning. This would enable us to know whether molecules or their location are damaged as a result of diseases such as Alzheimer’s.” Cancer research is another field that may be assisted by the technology. “one of the most fascinating questions today in cancer research is how the immune system affects cancerous cells. With our technology, we can see where cancerous cells are located in the tissue in relation to the location of immune system cells, and what their molecular contents are. One of the things we discovered using the new technology is that cancer cells act differently in the vicinity of immune system cells, and vice versa. In other words – show me your neighbors and I’ll tell you who you are.”

In October 2019, Alon arrived at the Faculty of Engineering at Bar Ilan, straight from MIT. These days he is forming his research group, which will focus on the technology that he developed. “First, we have to choose which questions to ask, that is, on which tissues do we think the technology would have the greatest impact. Next, we have to figure out what we want to do with the mountains of data we extract. Employing this technology on the tissue from a single patient produces 10TB of information, and analyzing this data becomes the heart of the matter. This is why I want to recruit MSc and PhD students from different backgrounds – computers, physics, data processing, biology and, of course, engineering – to get a better handle on how to cope with all this data.”

Alon’s technology stirs up interest in the private and academic sectors. These days, he is working on data analysis using tools built with the help of Toshiba. “Toshiba develops hard drives, information storage components, and it wants to know which technologies would generate high quality big data in the future. That’s what attracted them to our technology,” says Alon. The technology has also piqued the interest of molecular biologists: “Last February I participated in the Grand Challenge Cancer Research UK, an initiative designed to fund breakthrough research and find the technology of the future in cancer research. Ours made quite a stir.”