CRISPR Genome Editing Strategy Could Improve Rice, Other Crops

By Amy Quinton

Scientists at UC Davis and collaborators at the Joint BioEnergy Institute (JBEI) have used CRISPR technology to genetically engineer rice with high levels of beta-carotene, the precursor of vitamin A. The technique they used provides a promising strategy for genetically improving rice and other crops. The study in Nature Communications was published by a research team led by Pam Ronald, a professor in the Genome Center and the Department of Plant Pathology at UC Davis and Scientific Lead of Plant Pathology at JBEI.

Rice grains

UC Davis plant scientists used CRISPR technology to introduce beta-carotene, the precursor to vitamin A, into rice. The biofortified rice is shown on the right. Genetically modified “golden rice” enriched with carotene is already grown in the Philippines as a way to fight vitamin A deficiency. CRISPR could be a new route to such crop improvements. (Photo by Oliver Dong, UC Davis)

Rice is a staple food crop for more than half the world’s population. Golden Rice, a genetically engineered rice with high levels of beta-carotene, has been approved for consumption in more than five countries, including the Philippines, where vitamin A deficiency in children is widespread. Because of the social impact of the Golden Rice, the researchers chose the high beta-carotene trait as an example.

Conventional plant genetic engineering uses a bacterium or a particle gun to transfer genes encoding desired traits into the plant genome. In this case, researchers would use a bacterium to take beta-carotene producing genes and transfer them into the rice genome. But those transgenes can integrate into random positions in the genome, which can result in reduced yields.

“Instead, we used CRISPR to precisely target those genes onto genomic safe harbors, or chromosomal regions that we know won’t cause any adverse effects on the host organism,” said first author Oliver Dong, a postdoctoral scholar in the UC Davis Department of Plant Pathology and Genome Center.

Targeted insertion of genes

In addition, the researchers were able to precisely insert a very large fragment of DNA that does not contain marker genes. By contrast, conventional genetic engineering relies on the inclusion of marker genes in the inserted DNA fragment. These marker genes are retained when the plant is bred over generations, which can often trigger public concern and stringent regulations of the transgenic products before their entrance to the marketplace.

“Scientists have done targeted insertions before and without marker genes, but we haven’t been able to do it with such big fragments of DNA,” said Dong. “The larger the fragment of DNA, the more biological function or complex traits we can provide the plants.”

Dong said this opens up the possibility that genes controlling multiple desirable traits, such as having high levels of beta-carotene as well as being disease-resistant or drought-tolerant, can be clustered at a single position within the genome. This can greatly reduce subsequent breeding efforts.

Other authors include Shu Yu, Rashmi Jain, Nan Zhang, Phat Duong, Corrine Butler, Yan Li, and Li Tian from UC Davis; Anna Lipzen, Joel Martin, Kerrie Barry and Jeremy Schmutz at the the U.S. Department of Energy (DOE) Joint Genome Institute (JGI), a DOE Office of Science User Facility located at Lawrence Berkeley National Laboratory (Berkeley Lab).

The work was funded by the U.S. Department of Energy, the Winkler Family Foundation and the Innovative Genomic Institute.

Diving deeper into a genus of fungi with bioenergy potential

A new study in Nature Communications further investigates a genus of fungi whose vast biochemical diversity makes it important for bioenergy applications. 

The study, led by researchers at the Joint BioEnergy Institute, the the U.S. Department of Energy (DOE) Joint Genome Institute (JGI), a DOE Office of Science User Facility located at Lawrence Berkeley National Laboratory (Berkeley Lab), and the Technical University of Denmark, presents the first analysis of a section of Aspergillus fungi known as Flavi. The results are part of a long-term project to sequence the genomes of more than 300 Aspergillus fungi. 

“The genus Aspergillus is extremely diverse and the research outlined in this paper allowed us to deeply explore one group of Aspergilli in depth,” said Scott Baker, Biological Sciences Lead at the Environmental Molecular Sciences Laboratory, a national user facility at Pacific Northwest National Laboratory, and a scientist in JBEI’s Deconstruction division. “We were able to gain insight into the biochemical diversity of this section as well as understand the catalog of enzymes that these species use to digest plant biomass.”

The section contains several important species that can do both harm and good. For example, some species can infect and damage crops, while other species can produce secondary metabolites that can serve as biofuel and bioproduct intermediates. Many of the species also contain a large number of carbohydrate active enzymes, which digest plant biomass and are of interest to researchers working on converting bioenergy crops into sustainable biofuels.

“The genomes of these organisms encode a huge breadth of enzymatic diversity, from the ability to make novel secondary metabolites to being able to deconstruct plant biomass,” Baker said. “Sequencing their genomes is the first step to expanding the number of fungal genes that could be useful contributions to synthetic biology.” 

Photos courtesy of Mikael Rørdam Andersen, Technical University of Denmark.

Using Bioenergy Byproducts to Curb Greenhouse Gas

Researchers in the Joint BioEnergy Institute, the Energy Technologies Area at Berkeley Lab and UC Berkeley published a study analyzing how bioenergy byproducts can be beneficial for carbon sequestration and greenhouse gas mitigation in California, when used to improve soil quality on degraded lands.

Their findings predict that as bioenergy facilities scale up, bioenergy byproducts land application has the potential to meet half of the annual goal for working/natural lands greenhouse gas reduction in the State’s scoping plan for 2030.

Read their article published in Environmental Science & Technology.

Jay Keasling to receive AIChE’s Doing a World of Good Medal

Jay Keasling, JBEI’s chief executive officer, will be awarded the Doing a World of Good Medal by the American Institute of Chemical Engineers (AIChE) at their annual meeting on Nov. 10.

The Doing a World of Good Medal recognizes the achievements of an engineer whose work has had a positive impact on society and the world. Keasling, a pioneer of synthetic biology, will be recognized for his contributions to resource sustainability and human welfare, including a method for the inexpensive production of artemisinin, an antimalarial medicine. The award also recognizes his commitment to fostering secure and inclusive educational and working environments for people of all backgrounds.

“Dr. Keasling’s brilliant work, coupled with his passion to solve some of society’s most challenging global issues, has resulted in extraordinary advances in healthcare, sustainable fuels and the future of our environment,” said AIChE’s executive director and chief executive officer June Wispelwey. “He is a genuine example of AIChE’s ‘Doing a World of Good’ motto, and it is an honor to recognize him as this year’s medalist.”

Keasling is also a professor in the Departments of Bioengineering and of Chemical and Biomolecular Engineering at UC Berkeley. His research focuses on engineering microorganisms to produce useful chemicals. At JBEI, the Keasling Laboratory focuses on producing advanced biofuels and bioproducts using polyketide synthases.

Getting Teens Hooked on Stem

The Introductory College Level Experience in Microbiology (iCLEM) summer intensive is hosted and run by the Joint BioEnergy Institute (JBEI). First launched in 2008, iCLEM immerses local Bay Area students in the biological sciences – and gives them a taste of day-to-day life as a scientist – through an eight-week-long blended curriculum of instruction, hands-on basic laboratory skill training, and in-depth tours of working labs within JBEI, Lawrence Berkeley National Laboratory (which manages JBEI), and local biotech companies. The students, who receive a stipend so that they may attend the program in place of a summer job, utilize their newfound knowledge by conducting independent research projects and presenting their findings at the end of the program.

Read the story here and hear from the 2019 iCLEM cohort in this video.


Getting Teens Hooked on STEM

By Aliyah Kovner 

It’s 1 p.m. on a sunny afternoon in July – smack dab in the middle of summer break – and a perfect 75 degrees outside; but Jonathan Park is laser-focused. Though he could be strolling down a beach, or at home browsing social media, this 16-year-old is bent over a lab bench, intently pipetting reagents to run an Amplex Red Assay.

Park, a soon-to-be junior at Dublin High School, is part of the 2019 cohort of the Introductory College Level Experience in Microbiology (iCLEM) summer intensive, hosted and run by the Joint BioEnergy Institute (JBEI) in Emeryville. First launched in 2008, iCLEM immerses local Bay Area students in the biological sciences – and gives them a taste of day-to-day life as a scientist – through an eight-week-long blended curriculum of instruction, hands-on basic laboratory skill training, and in-depth tours of working labs within JBEI, Lawrence Berkeley National Laboratory (which manages JBEI), and local biotech companies. The students, who receive a stipend so that they may attend the program in place of a summer job, utilize their newfound knowledge by conducting independent research projects and presenting their findings at the end of the program.

“I didn’t really know what to expect, I thought maybe we would just come in and do some experiments here and there,” said Park, while on a break from the lab. He explained that he hadn’t been drawn to science until last year’s honors chemistry class challenged him in a way that got his attention. “I was like, okay, this is really interesting, I need to try this out. And iCLEM was there at just the right time. Being here has really shattered my idea of biology, chemistry and physics being these separate things – I’ve learned that they’re all just an integrated science that researchers use to do all these cool things, like making biofuels and actually saving the environment.”

Jonathan Park pipetting reagents at JBEI, in Emeryville, CA.

Jonathan Park pipetting reagents at JBEI.

The experience at iCLEM has motivated Park, who previously planned to study music, to pursue a double major with biochemistry when he attends college in 2021. If he follows through with his ambitions, Park will be in good company. According to Lauchlin Cruickshanks, iCLEM’s educational program administrator, 95% of past participants have gone on to continue their education at two or four-year colleges and universities, and 80% majored in science or engineering. Given that the program specifically recruits teens who face socioeconomic hurdles to higher education, this impressive attendance rate is a point of pride among the scientists and educators who make iCLEM happen.

Hoping to spread their prodigiously successful model beyond the confines of JBEI, a group of former and current scientific advisors have shared the iCLEM curriculum in the Journal of Microbiology & Biology Education.

“There are so many different curricula to teach basic microbiology and biochemistry already in journals, but I think one of the attractive things about this approach, and the reason it resonates with kids, is that we talk about science through the lens of sustainability,” said Jesus Barajas, the first author of the paper and a former scientific advisor for iCLEM. “Our overall goal is to teach these concepts by having students learn how to produce biofuels and bioproducts in a sustainable fashion. This is more meaningful, because if we want to think of them as the next generation of scientists, we don’t just want to train them to tackle the problems of today and tomorrow, but also for them to really understand the problems.”

The iCLEM 2019 cohort.

From the outset, iCLEM has been dedicated to nurturing budding scientists who would not otherwise have access to a college preparation scientific internship. Nearly all students are from low-income families, and many are also English language learners and/or the first generation to attend college. Clem Fortman and James Carothers, the program’s founders, came up with the premise for iCLEM during a conversation about what was lacking in STEM education. At the time, they were both postdoctoral researchers at JBEI and the Synthetic Biology Research Center (Synberc), a collaborating institution located in the same building.

“We talked about how a lot of the existing programs acted as a leg up for folks who already had a leg up. And it turned out that James and I shared the experience of having to work summers and weekends when we were teenagers,” said Fortman, who served as iCLEM’s scientific director for the first four years and is currently director of operations for the lab of Jay Keasling, JBEI’s CEO. “We didn’t have the resources or opportunities to go into the types of school camps and other stuff that can help get kids onto the STEM career track – something that is still the reality of life for many people, especially in the Bay Area.”

As the duo continued discussing the unmet needs in science education, Fortman excitedly realized that much of the fundamental laboratory work supporting JBEI and Synberc’s biofuels research, i.e., the tasks typically done by undergraduate students, could be used as a real-world foundation for teaching basic microbiology and biochemistry. With that conversation, the concept for iCLEM was born. Fortman and Carothers soon pitched their idea to Keasling, drawing upon their own career journeys as they emphasized that providing “opportunities to those who don’t have an easy pipeline into science” means small class sizes, providing financial assistance, and offering college preparation support. Their proposal was approved on the spot. 

Zoe Siman-Tov. (Credit: Marilyn Chung/Berkeley Lab)

“I had some really high expectations for iCLEM and [it has] surpassed them all. I love this program. It’s the highlight of my summer,” said participant Zoe Siman-Tov. “The things we got to do are things that you’d never be able to get to do in high school. And being able to do it myself has really cemented it in, and I’m very sure that I’d like to work in a lab.”

Over the next several years, iCLEM’s curriculum evolved organically, as the founding scientists and a rotating roster of advisors, enthusiastic mentors, and high-school teachers – who help lead the instruction-based portions of the program – refined and enriched their approach.

Raymundo Sanchez, a past student in the 2015 cohort, notes that iCLEM’s behind-the-scenes instructional model helped guide him toward his current interest in biological anthropology. He will soon begin his senior year at UC Santa Barbara as a double-major in the field, alongside Chicano/a studies. “I really love my majors and feel like they blend perfectly what I strive to do in the future, which is help out underrepresented communities by helping them gain better access to healthcare and education,” said Sanchez. “But I would have not even thought of all the different careers that are possible within STEM if it wasn’t for my internships, which were hard to find and only a handful of them were out there for underrepresented individuals. For STEM fields to become more diverse, I think it would be helpful to have more experiences, like iCLEM, that bring awareness and exposure to the many possibilities out there.”

Now that the details of iCLEM are widely available, Fortman and the rest of the team are optimistic that other programs with the same core tenets will indeed develop, and that more teens than could ever fit at the JBEI lab benches will soon be able to participate.

Looking back, the group regards the many hours of volunteered time spent developing the curriculum and building iCLEM into the experience it is today as a necessary contribution toward the long-overdue, large-scale shift that is happening throughout the education framework. “I believe that the STEM fields are trying to be more inclusive than they were,” said Fortman. “But there needs to be educational equality much earlier than when we’re intervening, starting at day one.”

iCLEM is currently funded by JBEI, which is supported by the DOE Office of Science; the Amgen Foundation, administered through UC Berkeley; and the Heising-Simons Fund.

Keasling Featured in NHK World, Japan’s Public TV Station

Jay Keasling, JBEI’s Chief Executive Officer, was featured in NHK World’s interview program “Direct Talk”. Keasling, a pioneer of synthetic biology, talks about the impact that this interdisciplinary technology can have in people’s lives as well as addresses its safety concerns.

Direct Talk is a program that interviews leaders, visionaries and pioneers who shape the world and is broadcast to 300-million households in 160 countries in six different language subtitles.

Watch the interview

More Investment Needed for Machine Learning for Bioengineering

In an opinion piece published July 19 in ACS Synthetic Biology, Hector Garcia Martin and Tijana Radivojevic of the Joint BioEnergy Institute collaborated with Pablo Carbonell of the Manchester Institute of Biotechnology’s SynBioChem Centre, to highlight the opportunities in a radical new approach to bioengineering that leverages the latest disruptive advances in machine learning.

The opinion piece entitled “Opportunities at the intersection of Synthetic Biology, Machine Learning, and Automation” puts forward a new approach to bioengineering that may significantly accelerate metabolic engineering for the creation of all types of bioproducts: from biofuels to biomaterials and medical drugs. According to the authors sustained investment in the intersection of the three domains and strong multidisciplinary collaboration are key to drive forward predictive biology and produce improved machine learning algorithms.

Machine learning methods make inferences from raw data using sophisticated algorithms and powerful computers. In order to be trained, machine learning techniques need large amounts of data. Yet challenges remain on how to acquire large-scale high-quality biological data. The authors see automation as the best way to produce the quantity and quality of data needed for effective machine learning. In the long run the intersection of synthetic biology, machine learning, and automation will helps us better design biological systems for a renewable bioeconomy, and it sets the base for a better understanding of biology in general.

Related Information:

New Machine Learning Approach Could Accelerate Bioengineering

Garcia Martin Lab Website

Could Synthetic Biology Stop Global Warming?, Latino USA

Héctor García Martín, Deputy Vice President of JBEI’s Biofuels and Bioproducts Division spoke to Latino USA about the emerging field of synthetic biology and how it allows scientists to re-engineer biological systems for new purposes, namely how it could lead to new biofuels which would reduce the release of carbon dioxide—the main cause of global warming. Listen here