Weizmann Institute scientists have engineered bacteria to create sugar from the greenhouse gas carbon dioxide. All life on the planet relies, in one way or another, on a process called carbon fixation – the ability of plants, algae and certain bacteria to “pump” carbon dioxide (CO2) from the environment, add solar or other energy and turn it into the sugars that are the required starting point needed for life processes.
Prof. Ron Milo’s lab at the Institute’s plant and environmental sciences department found that the ability to improve carbon fixation is crucial for our ability to cope with future challenges. This includes the need to supply food to a growing population on shrinking land resources while using less fossil fuel.
At the top of the food chain are different organisms (some of which think, mistakenly, that they are “more advanced”) that use the opposite means of survival – they eat sugars (made by photosynthetic plants and microorganisms) and then release carbon dioxide into the atmosphere. This means of growth is called “heterotrophism.” Humans are, of course, heterotrophs in the biological sense because the food they consume originates from the carbon fixation processes of nonhuman producers.
The Rehovot scientists wanted to know if it was possible to “reprogram” an organism that is higher in the food chain and consumes sugar and releases carbon dioxide,so that it will consume the gas from the environment and produce the sugars it needs to build its body mass. Led by Dr. Niv Antonovsky who works in the institute, scientists rose to this challenge by inserting the metabolic pathway for carbon fixation and sugar production (the so-called Calvin cycle) into the bacterium E. coli, a known organism that eats sugar and releases carbon dioxide.
The metabolic pathway for carbon fixation is well known, and Milo and his group reckoned that, with proper planning, they would be able to attach the genes containing the information for building it into the bacterium’s genome. Yet the main enzyme for plants to fix carbon, RuBisCO, uses as a substrate for the CO2 fixation reaction a metabolite that is toxic for the bacterial cells. Thus, the design had to include precise regulation of the expression levels of the various genes across this multi-step pathway.
In one way, the team’s well-thought-out plan was a resounding success: The bacteria did indeed produce the carbon fixation enzymes, and these were functional. But the machinery, as a whole, did not “deliver the goods.” Even though the carbon fixation machinery was expressed, the bacteria failed to use CO2 for sugar synthesis, relying instead on an external supply of sugar. “Of course, we were dealing with an organism that has evolved over millions of years to eat sugar, not CO2,” says Antonovsky. “So we turned to evolution to help us create the system we intended.”
Antonovsky, Milo and the team (which included Shmuel Gleizer, Arren Bar-Even, Yehudit Zohar, Elad Herz and others) next designed tanks called “chemostats,” in which they grew the bacteria, gradually nudging them into developing an appetite for CO2. Initially, along with ample bubbles of CO2, the bacteria in the tanks were offered a large amount of pyruvate, which is an energy source, as well as barely enough sugar to survive. Thus, by changing the conditions of their environment and stressing them, the scientists forced the bacteria to learn, by adaptation and development, to use the more abundant material in their environment. A month went by, and things remained fairly static. The bacteria did not seem to “get the hint.” But at around a month and a half, some bacteria showed signs of doing more than “just surviving.” By the third month the scientists were able to wean the evolved bacteria from the sugar and raise them on CO2 and pyruvate alone. Isotope labeling of the carbon dioxide molecules revealed that the bacteria were indeed using CO2 to create a significant portion of their body mass, including all the sugars needed to make the cell.
When the scientists sequenced the genomes of the evolved bacteria, they found many changes scattered throughout the bacterial chromosomes. “They were completely different from what we had predicted,” said Milo. “It took us two years of hard work to understand which of these are essential and to unravel the ‘logic’ involved in their evolution.” Repeating the experiment (and again waiting months) gave the scientists essential clues for identifying the mutations necessary for changing the E. coli diet from one based on sugar to one using carbon dioxide.
“The ability to program or reengineer E. coli to fix carbon could give researchers a new toolbox for studying and improving this basic process.”
Although currently the bacteria release CO2 back into the atmosphere, the team envisions that in the future their insights might be applied to creating microorganisms that soak up atmospheric CO2 and convert it into stored energy or to achieving crops with carbon fixing pathways, resulting in higher ields and better adaption to feeding humanity.U MENTORS US SCIENCE STUDENTS More than two dozen undergraduate science majors from Yeshiva College, Stern College for Women, Brooklyn College, Cornell University, the University of Maryland, University of Pennsylvania and the Illinois Institute of Technology have participated in the sixth annual Summer Science Research Internship Program, a joint Bar-Ilan University and Yeshiva University initiative. The program enabled students to gain hands-on experience in emerging scientific fields while being mentored by some of Israel’s finest scientists.
During the seven-week research experience, students conducted intensive internships in BIU’s research labs with faculty members from the Bar-Ilan Institute for Nanotechnology and Advanced Materials, Gonda (Goldschmied) Multidisciplinary Brain Research Center, Faculty of Engineering, Mina and Everard Goodman Faculty of Life Sciences and the departments of mathematics, chemistry and psychology.
Prof. Ari Zivotofsky of BIU’s Interdisciplinary Brain Sciences Program served as director of the program, which ran until August 8.
“This program provides talented US university science students the opportunity to become embedded in a high caliber Israeli university lab, thereby experiencing rather than just hearing about what it’s like to live, learn and research in Israel. In the labs they become part of a team and contribute to ongoing projects. Spending their summer with a like-minded group of peers fosters a commitment to research, Israeli science and religious Zionism,” Zivotofsky said.
Briana Friedman from Stern College, who wants to become a physician, worked with Prof. Ron Goldstein of the BIU Faculty of Life Sciences on a project that once would have been thought of as science fiction – converting one kind of a cell into another.
“When I went to college and graduate school, we learned that once cells differentiate or take on a specific identity and functional role in the body, this is a permanent choice. For the past five to 10 years it has been shown that manipulating the expression of specific genes (making the cells make “foreign” proteins) can change their identity,” said Goldstein.
“My student’s project was to recapitulate and advance this technique, to make human neurons of the peripheral nervous system (those not located in the brain) for our studies of the chicken pox/shingles virus. In our current technology, we use a mishmash of brain and peripheral neurons, while ideally, we would use only those really infected in the disease.
She did the molecular biology work necessary to make special viruses that are used to introduce foreign genes into cells,” he added Based on the students’ academic background and interest, Zivotofsky matched students with mentors and research assignments that would both enhance their summer experience and promote individual growth and career development. While the focus is primarily on lab work, the program also included trips to scientific and industrial sites around the country, Israel Aerospace Industries, Teva Pharmaceuticals and the Agriculture Research Organization (Volcani Center), as well as a series of lunch meetings with BIU faculty members.