Dr. Roee Amit, the “new face” in the Faculty of Biotechnology and Food Engineering at the Technion, in collaboration with researchers from Caltech where he did a post-doctoral fellowship, has succeeded in building a “biological Rosetta Stone” within a bacterium, reports the prestigious science journal, Cell. The researchers have, in essence, developed a new understanding of the group of bacterial controllers called Enhancers. These objects constitute a DNA sequence that is not, however, a gene, to which proteins attach. These sequences are common to all living creatures and may be thought of as modular objects that can combine “input” or signals. Gene expression is usually the result of a specific combination of a number of proteins, which means that researchers may be able to control the gene expression.
“One of the central discoveries in biology in the post-genome era is the understanding that the main factor contributing to the differences between organisms (for instance, between mice and men) is not the result of genes,” explains Dr. Roee Amit. “The difference lies in the algorithm or program that determines when, where and how much a given gene will be expressed. In the past few years a new picture of the genome is becoming clearer, and as a result, a model in which the genome is perceived as a complex tool for storage and dissemination of information is also taking shape.”
The objective of Dr. Amit’s research is to decode the “software” that controls the process and use this knowledge to develop medical applications. “In order to do this, we intend to create a ‘Rosetta Stone’ of the genetic control (the original Rosetta Stone is a granodiorite stele that had the same ancient text inscribed on it in three different languages, as a result of which archaeologists were able to decipher Egyptian hieroglyphics),” says Dr. Amit. “This tool will be used to ‘hack’ the control program of real organisms and consequently allow us to ‘write’ new programs – which do not exist in nature – for medical purposes, environmental applications, etc. Synthetic biology is a new branch of life science, which takes a constructive/building approach. It attempts to use biological components to construct new biological systems that do not exist in nature. It forces us to really examine our understanding by requiring us to use what we think we understand in order to create biological functions. It allows us to ask why evolution “locked onto” specific patterns, to imagine and create new biological functions and forces us to work in a multidisciplinary fashion.”
The approach of synthetic biology researchers is based on using characteristic genomic components and arranging them together (or “wiring” them to each other) in new architectures. In the next stage they develop patterns based on thermodynamic models, and in the end, they analyze the output using their model. By doing this, they can draw basic programming principles that permit them to translate the architecture and the sequence into computer algorithms. “If we succeed in writing a sequence that predicts our output based on programming rules that we found in the ‘Rosetta Stone’ – we can then use this ‘key’ to decipher certain sequences that appear in the genome,” says Dr. Amit.
In the paper in Cell, Dr. Amit and his colleagues showed that they can use this approach to develop a new understanding of enhancers among bacteria. They demonstrated that new artificial and functional bacterial enhancer programs can be built, which led to the development of a biophysical model for the control program, or “machine code”. The researchers note that the type of computation that takes place in this context is reminiscent of analogue computing processes more than digital ones. “This Rosetta Stone, in the bacterial context, has enabled us to formulate a new understanding, or qualitative model, for many examples of bacterial enhancers in nature, most of which have never been analyzed,” stresses Dr. Amit. “Now we can understand, at least partially, the programs encoded into many natural enhancers that have not yet been studied in the lab.”
How did you get to science at all?
“I think I was born like this,” he smiles. “The person who encouraged me was my maternal grandfather, Rafael Balgoor. I was his oldest grandson. He was an educator who was involved in the area of dyslexia. At the start of his career he was an actor in the “HaBima” repertoire company and then afterwards a soldier in the Jewish Brigade, a storyteller, a lecturer, a man of letters. He stimulated my scientific curiosity and talked about scientists with high regard. “
In school they didn’t encourage your scientific curiosity?
“In Israel, school didn’t leave its mark on me, except for a history and civics teacher in the Reali School called Miriam Mikolovsky, may she rest in peace. She was a very special teacher. When I was 13 years old, my family went to the U.S., to New Jersey and there too school wasn’t a big hit, except for soccer, tennis and the annual science fair. During one of my vacations in Israel, together with my grandfather I built a model airplane out of paper. We designed it all – the weight, wing span, etc. When I returned to my parents’ home in New Jersey, my dad gave me a computer program that matched up all the data and then afterward allowed me to design an improved paper model airplane. The success that year ignited my appetite and the next summer I enhanced the project. I built the wings from wood so that the plane could liftoff with force and started looking into model airplanes made of balsa wood. Even though this project was a significant improvement over the paper model, the judges at the fair did not rate it highly and I didn’t get very far. The next year I lost interest but despite this my science teacher entered the project in the competition and this project actually won a prize without my active participation. This was a bitter disappointment but also an important lesson in the character of the real world of science.”
Dr. Amit did his undergraduate degree in physics. He recalls that period as challenging. “The creativity and research always attracted me more than the frontal classroom instruction,” he explains.
After completing his undergraduate studies, he returned to Israel, served in the army and then to the Weizmann Institute to do his graduate degree. There he began to get interested in “God’s operating system,” as he calls it. During his doctoral program (when he moved to the area of biology) he met his wife, Naomi, who was doing her PhD in biology. His post-doc was in synthetic biology, which Dr. Amit defines as an important revolution in many areas – basic research and an understanding of how information is encoded and linked through the genome. “This new field forces us to examine whether what we think we understand – is actually true, by building new systems,” he says. “It also enables us to ask why evolution locked onto specific patterns and forces us to adopt a multi-disciplinary approach in our work.”
Dr. Amit believes that synthetic biology will bring about the development of smart drugs for diseases that today are incurable. “And not just medications,” he adds. “There is no limit to one’s imagination here. We will perhaps be able to help people see new colors, which do not yet even have names, or develop bacteria that will help clear mines from old minefields and even send a spacecraft to Mars with enough fuel for a one-way trip, carrying bacteria that will produce the fuel it needs to return home.”
This sounds like science fiction.
Dr. Amit laughs. “I am trying to introduce real content into the illusion and dream. And the Technion is the ideal platform for this, because it is an engineering school with strong links to industry. This is a new field that may be the high tech of bio tech.”