Congratulations to MCB & Chemistry Professor Jennifer Doudna, who is one of five recipients of this year's Medal of Honor from the American Cancer Society! Medal of Honor recipients are "distinguished individuals who have made valuable contributions in the fight against cancer through basic research, clinical research and cancer control."
Professor Doudna joined four others in receiving the award at a ceremony today in Washington, DC: former Vice President Joe Biden, CRISPR co-inventor Emmanuelle Charpentier, geneticist Charis Eng, and cancer researcher Michael Thun.
Two new publications from MCB Professor David Raulet and collaborators focus on the role of natural killer cells in anti-tumor responses. Natural killer cells are a type of white blood cell that have an important role in defending against virally infected cells and tumors.
The first, published in Journal of Clinical Investigation, demonstrated that checkpoint inhibitors, a well-established cancer immunotherapy, have the ability to activate natural killer cells. In the future, researchers hope to better understand the factors that influence natural killer cell activation for use in improved immunotherapies. Read more...
The second paper, published in Immunity, is a collaboration with the lab of MCB Professor Russell Vance. It shows that cGAMP from tumors promotes natural killer anti-tumor immune responses. Read more...
A new paper from the lab of Professor of MCB & Chemistry and HHMI Investigator Jennifer Doudna identifies and details the power of the smallest CRISPR system found to date, Cas14. CRISPR-Cas14 was first discovered in archaea with some of the smallest known genomes and is especially effective in editing viral genes or genes in small cells.
Due to its effectiveness in targeting and cutting single-stranded DNA, researchers have identified Cas14's potential use in improving rapid CRISPR diagnostic tests for ailments such as cancer and infectious diseases.
Many Archaea like these have CRISPR systems to protect themselves from attacking viruses. The smallest CRISPR system found to date, Cas14, was found in the genome of one such Archaea, which scientists have so far been unable to grow in the lab.
An ancient group of microbes that contains some of the smallest life forms on Earth also has the smallest CRISPR gene-editing machinery discovered to date.
The peewee protein machinery, dubbed Cas14, is related to but one-third the size of the Cas9 protein, the business end of the revolutionary gene-editing tool CRISPR-Cas9. While Cas9 was isolated from bacteria, Cas14 was found in the genome of a group of Archaea – a primitive relative of bacteria – that contains some of the smallest cells and smallest genomes known.
Cas9 and other Cas proteins are part of a defense system evolved by microbes to protect themselves from viruses. All are targeted enzymes that seek out and bind very selectively to a specific DNA or RNA sequence – in microbes, those that match sequences stored in its CRISPR memory banks after earlier viral infections – and then cuts the DNA or RNA to disable the new invader.
Like Cas9, Cas14 has potential as a biotech tool. Because of its small size, Cas14 could be useful in editing genes in small cells or in some viruses. But with its single-stranded DNA cutting activity, it is more likely to improve rapid CRISPR diagnostic systems now under development for infectious diseases, genetic mutations and cancer.
“For molecular diagnostics, you want to be able to target double-stranded DNA, single-stranded DNA and RNA,” said Lucas Harrington, a UC Berkeley graduate student and first author of a paper reporting the discovery. “Cas12 is really good at double-stranded DNA recognition, Cas13 is really good at single-stranded RNA recognition and now Cas14 completes the set: it is really good at single-stranded DNA recognition.”
Cas14 is similar to Cas12 and Cas13 in that, after binding to its target DNA sequence, it begins indiscriminately cutting all single-stranded DNA inside a cell. Cas9, in contrast, binds and cuts only the targeted DNA.
The wanton cutting of DNA is a possible disadvantage in therapy, but a great advantage in diagnostics. The Cas14 protein can be paired with a fluorescent marker attached to a piece of single-stranded DNA. When Cas14 binds to its target DNA sequence – a cancer gene or a gene in infectious bacteria – and starts cutting DNA, it will also cut the DNA linked with the marker, generating a fluorescent signal.
“Cas14 targets single-stranded DNA in a much more specific way than Cas12 does,” added Harrington’s colleague, Janice Chen, who recently received her Ph.D. from UC Berkeley. “That was a really unexpected finding. Because it is so small, we barely thought it could work, but actually it is super-specific, which makes it also a really powerful addition to the diagnostic toolbox.”
Harrington, Chen and their colleagues, including CRISPR-Cas9 inventor Jennifer Doudna, a UC Berkeley professor of molecular and cell biology and of chemistry, have adapted Cas14 to work with their diagnostic system, called DETECTR, which now uses Cas12 and Cas13 to quickly detect the presence of infectious organisms and genetic mutations. Harrington, Doudna and Chen are co-founders of a company, Mammoth Biosciences, that is commercializing DETECTR.
The discovery will be reported online Oct. 18 in advance of print publication in the journal Science. Doudna is a Howard Hughes Medical Institute investigator, co-director of the Innovative Genomics Institute and a faculty scientist at Lawrence Berkeley National Laboratory. Banfield is the microbiology lead for IGI and a Berkeley Lab affiliate.Mining metagenomes
The Cas14 protein was found by co-first authors Harrington and David Burstein, now a professor at Tel Aviv University in Israel, as they looked for Cas variants in a databaseof microbial genomes created over the past 15 years by their UC Berkeley colleagues — a team led by Jill Banfield, professor of earth and planetary science and of environmental sciences, policy and management. The genomes, numbering in the tens of thousands, were obtained by metagenomic sequencing of all the DNA in samples from a variety of exotic environments. Cas14 was found in the genome of Archaea sequenced from groundwater samples obtained from a toxic cleanup site in Rifle, Colorado.
The smallest known CRISPR gene-editing system was found in a database of all microbial genomes sequenced from soil at a toxic cleanup site in Rifle, Colorado. (Iris Burstein image)
Two years ago, Harrington and Burstein discovered other small Cas proteins, CasX and CasY, while mining the metagenomics database.
Cas14 is half the size – between 400 and 700 amino acids in length – of CasX and smaller than all other known Cas systems, which range in length from 950 to 1,400 amino acids.
“By happenstance, we found these very small proteins, which other people just throw away because they don’t look like previously known CRISPR systems. They are too small,” Harrington said. “We decided, what the heck, let’s give it a shot. We tested it out and we were actually shocked to find that these were actual functional systems.”
Finding the gene for Cas14 in the database was only the beginning. Most Cas proteins to date have been found in bacteria, and thus work well in the standard lab bacterium, E. coli. But Cas14 is from Archaea – and a group of the smallest of the Archaea, called DPANN. All Cas proteins incorporate bits of RNA for targeting and binding, but Cas14 won’t work with CRISPR-Cas9 RNAs, so the team also had to fish out of the database the two RNAs that must be present for Cas14 to function.
In addition, DPANN Archaea cannot be grown in the lab – they appear to be parasitic or in some way dependent on other larger Archaea – so the researchers had to create the right environment in a test tube.
Consistent with its origins in a more primitive microbe, the slimmed down Cas14 appears to be a more primitive version of the larger and more complex Cas9 and Cas12 proteins, Harrington said, hinting that the molecules have evolved over eons to be more specialized. The researchers hope to learn from such primitive Cas proteins, which are the essential components of the Cas enzyme, so that they can design the most compact and sleek gene cutters they can.
Harrington noted that the metagenomic mining turned up various versions of Cas14 that may prove to be useful biotech tools. “One amazing thing … is just how diverse these systems are,” he said. “We’ve described more than 40 new CRISPR-Cas14 systems and eight different subtypes. This opens up the floodgates for investigation of these new CRISPR systems.”
Co-authors with Harrington, Burstein, Chen, Doudna and Banfield are Enbo Ma, Isaac Witte, Joshua Cofsky of UC Berkeley and David Paez-Espino and Nikos Kyrpides of the Department of Energy’s Joint Genome Institute in Walnut Creek, California. The metagenomic datasets mined by the group are available in JGI’s Integrated Microbial Genomes & Microbiomes (IMG/M) system, the largest collection of microbial genes, currently at 55 billion and growing.
The work was funded by the National Science Foundation, U.S. Department of Energy, Innovative Genomics Institute and Paul Allen Institute.
Programmed DNA destruction by miniature CRISPR-Cas14 enzymes (Science)
CRISPR scissors, Cas12a, enables cutting-edge diagnostics (Feb. 15, 2018)
Compact CRISPR systems found in some of world’s smallest microbes (Dec. 22, 2016)
A vineyard in California’s central coast is an example of industrialized agriculture. (Photo by Steve Zmak)
With a body the size of a fist and wings that span more than a foot, the big brown bat must gorge on 6,000 to 8,000 bugs a night to maintain its stature. This mighty appetite can be a boon to farmers battling crop-eating pests.
But few types of bats live on American farms. That’s because the current practice of monoculture – dedicating large swathes of land to a single crop – doesn’t give the bats many places to land or to nest.
Diversifying working lands – including farmland, rangeland and forests – may be key to preserving biodiversity in the face of climate change, says a new review paper published this week in Science by conservation biologists at the University of California, Berkeley.
Diversification could be as simple as adding trees or hedgerows along the edges of fields, giving animals like birds, bats and insects places to live, or as complex as incorporating a patchwork of fields, orchards, pasture and flowers into a single working farm.
These changes could extend the habitat of critters like bats, but also much larger creatures like bears, elk and other wildlife, outside the boundaries of parks and other protected areas, while creating more sustainable, and potentially more productive, working lands.
“Protected areas are extremely important, but we can’t rely on those on their own to prevent the pending sixth mass extinction,” said study co-author Adina Merenlender, a Cooperative Extension Specialist in the Department of Environmental Science, Policy and Management at UC Berkeley. “This is even more true in the face of climate change, because species will need to move around to adapt to shifts in temperature and climate.”A win-win for wildlife and for farms
Maintaining even small pieces of the original landscape – even a single tree– can help conserve the original diversity of species, Merenlender said. Clearing oak woodlands and shrublands to establish large vineyards hits many native species hard. Animals that are well adapted to urban and agricultural areas, such as mockingbirds, house finches and free-tail bats, continue to flourish, while animals that are more sensitive to disturbance, like acorn woodpeckers, orange-crowned warblers and big brown bats, begin to drop away. “If you can leave shrubs, trees and flowering plants, the habitat suitability - not just for sensitive birds but also for other vertebrates – goes way up,” Merenlender said. This is true not only in California’s vineyards, but on working lands around the world.
The Benzinger Family Winery is a diversified vineyard in Sonoma County. (Photo by Corey Luthringer)
Incorporating natural vegetation makes the farm more hospitable to more creatures, while reducing the use of environmentally degrading chemicals like herbicides, pesticides and man-made fertilizer.
The ideal farming landscape includes woodland pastures and vegetable plots bumping up against orchards and small fields, said Claire Kremen, a professor in the Department of Environmental Science, Policy and Management. Integrating livestock produces manure which can fertilize the crops, while those same crops produce feed for livestock. Birds and bats provide pest control, and bees boost crop production by pollinating plants.
“It is possible for these working landscapes to support biodiversity but also be productive and profitable,” Kremen said. “And ultimately, this is where we have to go. We just can’t keep mining our soils for their fertility and polluting our streams – in the end, this will diminish our capacity to continue producing the food that we need. Instead, we must pay attention to the species, from microbes to mammals, that supply us with critical services, like pollination, pest control and nutrient cycling”
“We have some amazing diversified farms, sustainably managed forests and species-rich rangelands here in California that exemplify working lands for conservation around the world,” Merenlender said. “We are calling for a scaling up of this approach around the world, and to do that we champion community-based action and more supportive polices” Kremen concludes.
CONTACTSThursday, October 18, 2018 - 11:15 byline: By Kara Manke Legacy: section header item: Date: Thursday, October 18, 2018 - 11:15 headline_position: Top Left headline_color_style: Normal headline_width: Long caption_color_style: Normal caption_position: Bottom Left
A new paper by Professor of the Graduate School Bruce Ames, published in Proceedings of the National Academy of Science, argues that a set of vitamins and minerals that are lacking from many Americans' diets may be key to defending against many chronic diseases and promoting healthy aging.
The publication is the culmination of a decade of research completed at Children's Hospital Oakland Research Institute (CHORI) and "concludes that healthy aging can be extended by ingesting optimal levels of 30 known vitamins and essential minerals, and he suggests that these, along with 11 additional substances not currently classified as vitamins, should be recognized as essential 'longevity vitamins' because of their potential to extend a healthy life."
MCB Professor and HHMI Investigator Barbara Meyer has been elected to the National Academy of Medicine, which recognizes researchers who have made major contributions to the advancement of medical sciences, health care, and public health.
In her prolific career, Meyer has been recognized for her "groundbreaking work on chromosome dynamics that impact gene expression, development, and heredity using the nematode as a model organism."
600 million people in Sub-Saharan Africa lack access to electricity. To meet these power needs, a mix of large public-run utility grids and standalone systems will be necessary for universal access in the region. Governments, aid organizations, and scientists are working to understand which electricity grid solution would be most cost-effective and reliable across urban, peri-urban, and rural areas.
Standalone, or “decentralized” electricity systems—most often solar power with battery storage—are usually thought to be too expensive compared to large state-run grids in all but the most remote locations. However, declining costs of solar and new battery technologies are changing the best pathways to deliver reliable power to people that currently lack access to electricity. New UC Berkeley research published today in Nature Energy finds that decentralized electricity systems in sub-saharan Africa can be designed for extremely high reliability, and that this may come at remarkably low costs in the future.
Jonathan Lee, a PhD candidate in the Energy and Resources Group (ERG) and Associate Professor Duncan Callaway worked with more than 10 years of solar data from NASA and developed an optimization model that determines the lowest cost way to build a standalone system given component costs and a target reliability. At current costs, their model indicates that most regions in Sub-Saharan Africa can get 95% reliable power—meaning customers can use electricity from some combination of solar panels and batteries 95% of the time—for roughly USD$0.40 per kWh. Though that cost is high relative to current grid costs, their model indicates that with aggressive but plausible future cost declines in decentralized system costs, largely in batteries, these costs would drop to levels competitive with the grid in many parts of the continent in less than a decade.
Because their model explicitly considers reliability as a design input, the researchers were able to study how costs change with each "9" of reliability—for example from 90% to 99%, or 99% to 99.9%. They calculate that, in their aggressive cost decline scenario, this “reliability premium” could be under $0.04 per kWh per 9 of reliability. For example, using this model, raising the reliability of service by one 9 would increase operating costs for a small refrigerator—which needs to have high reliability for medical facilities—by under one dollar per month.
“These low reliability premiums suggest that customers would have incredible autonomy to choose the quality of their electricity service, and this could be an important piece of the puzzle in expanding electricity access across populations with different reliability needs,” said Callaway.
However the researchers also point out that, in the current environment where many national grids in sub-saharan Africa are plagued by poor reliability and budget deficits, there are risks in this changing technology landscape. Customers that currently have grid access might choose to stop using the grid, especially in regions where grid costs are high or reliability is low, and this could make it difficult for utilities to continue with their current business model.
"Looking forward, our results indicate that utilities and governments in the region need to take decentralized solar very seriously; not just in remote areas, but in places close to the grid as well,” said Lee. “If governments aren’t proactive, they will put a lot of pressure on existing grids to significantly improve reliability and keep costs low."Media contacts and additional information
- Associate Professor Duncan Callaway, email@example.com
- PhD candidate Jonathan Lee, firstname.lastname@example.org
- To allow researchers, infrastructure planners, and industry stakeholders to conduct their own analysis using different technical and economic assumptions, the researchers have made their model publicly available as a web application here.
Image: Date: Monday, October 15, 2018 - 08:15 Legacy: section header item: Date: Tuesday, August 21, 2018 - 15:15 headline_position: Top Left headline_color_style: Normal headline_width: Long caption_color_style: Normal caption_position: Bottom Left News/Story tag(s): Research News
The 1972 Clean Water Act has driven significant improvements in U.S. water quality, according to the first comprehensive study of water pollution over the past several decades, by researchers at UC Berkeley and Iowa State University. The team analyzed data from 50 million water quality measurements collected at 240,000 monitoring sites throughout the U.S. between 1962 and 2001. Most of 25 water pollution measures showed improvement, including an increase in dissolved oxygen concentrations and a decrease in fecal coliform bacteria. The share of rivers safe for fishing increased by 12 percent between 1972 and 2001.
The Clean Water Act has decreased measures of water pollution in U.S. lakes, streams and rivers.
Despite clear improvements in water quality, almost all of 20 recent economic analyses estimate that the costs of the Clean Water Act consistently outweigh the benefits, the team found in work also coauthored with researchers from Cornell University. These numbers are at odds with other environmental regulations like the Clean Air Act, which show much higher benefits compared to costs.
“Water pollution has declined dramatically, and the Clean Water Act contributed substantially to these declines,” said Joseph Shapiro, an associate professor of agricultural and resource economics. “So we were shocked to find that the measured benefit numbers were so low compared to the costs.”
The researchers propose that these studies may be discounting certain benefits, including improvements to public health or a reduction in industrial chemicals not included in current water quality testing.
The analyses appear in a pair of studies published in the Quarterly Journal of Economics and the Proceedings of the National Academy of Sciences.Cleaning up our streams and rivers
Adding up all the costs and benefits — both monetary and non-monetary — of a policy is one way to value its effectiveness. The costs of an environmental policy like the Clean Water Act can include direct expenditures, such as the $650 billion in spending due to grants to municipalities, and indirect investments, such as the costs to companies to improve wastewater treatment. Benefits can include increases in waterfront housing prices or decreases in the travel to find a good fishing or swimming spot.
The researchers conducted their own cost-benefit analysis of the Clean Water Act municipal grants, and combined it with 19 other recent analyses carried out by hydrologists and the EPA. They found that, on average, the measured economic benefits of the legislation were less than half of the total costs. However, these numbers might not paint the whole picture, Shapiro said.
“Many of these studies count little or no benefit of cleaning up rivers, lakes, and streams for human health because they assume that if we drink the water, it goes through a separate purification process, and no matter how dirty the water in the river is, it’s not going to affect people’s health,” Shapiro said. “The recent controversy in Flint, MI, recently seems contrary to that view.”
“Similarly, drinking water treatment plants test for a few hundred different chemicals and U.S. industry produces closer to 70,000, and so it is possible there are chemicals that existing studies don’t measure that have important consequences for well-being,” Shapiro said.
Even if the costs outweigh the benefits, Shapiro stresses that Americans should not have to compromise their passion for clean water — or give up on the Clean Water Act.
“There are many ways to improve water quality, and it is quite plausible that some of them are excellent investments, and some of them are not great investments,” Shapiro said. “So it is plausible both that it is important and valuable to improve water quality, and that some investments that the U.S. has made in recent years don’t pass a benefit-cost test.”
Catherine L. Kling, professor of agricultural and life sciences and environmental economics and Cornell University, is a co-author on the Proceedings of the National Academy of Sciences paper.
Research funding was provided by the U.S. Department of Agriculture through the National Institute of Food and Agriculture Hatch Project IOW03909 and Award 2014-51130- 22494 and a National Science Foundation Award SES-1530494. Much of the research was completed while Shapiro was at Yale University.Tuesday, October 9, 2018 - 13:30 byline: Kara Manke Legacy: section header item: Date: Tuesday, October 9, 2018 - 13:30 headline_position: Top Left headline_color_style: Normal headline_width: Long caption_color_style: Normal caption_position: Bottom Left News/Story tag(s): Research News
MCB Postdoc Polina Kosillo has been awarded a NARSAD Young Investigator grant from the Brain & Behavior Research Foundation. The grant provides up to $70,000 over 2 years to promising young neurobiology researchers who study brain & behavioral disorders.
Kosillo studies the impact of dopamine dysfunction on mental disorders, such as ADHD and anxiety disorders. She is a member of the lab of MCB Assistant Professor Helen Bateup.
In this month’s Student Spotlight, senior Sophie Babka shares her experiences getting involved in environmental policy and action, from an internship with the California Environmental Protection Agency to attending the recent Global Climate Action Summit.Sophie Babka.
Why did you choose to study environmental science?
I want a career that focuses on solutions to environmental degradation and climate change mitigation. To prepare myself for this role, I took a multidisciplinary approach to learning more about and solving these problems by studying environmental sciences and public policy. Within this major and minor, I’ve had the opportunity to take courses emphasizing the science and engineering behind climate change while further gaining an understanding about how to create effective policies. By combining these two fields I hope to be prepared to work towards creating more science-based policies for tackling anthropogenic climate change.
I’m currently working on my senior thesis, which is assessing compostable plastics and trying to understand how many of these products are actually composted. This has been a really interesting process and has allowed me to learn about California’s waste management strategies and the implications compostable plastics have on compost facilities.
Sophie posing with a giant polar bear brought in for the Global Climate Action Summit.
You attended the Global Climate Action Summit last month—what were some key takeaways from that experience?
Participating in the Summit was incredible opportunity to witness powerful advocates coming together to increase momentum to fight the severe global consequences of climate change. Over 3,000 delegates attended the Summit, including some of the most notable UC Berkeley faculty members, including David Ackerly, Daniel Kammen, and Whendee Silver. While the summit was occuring, Hurricane Florence and other major weather incidents devastated countries around the world, showing how necessary climate action is to prevent increased extreme weather events such as these.
At the start of the week, California Governor Jerry Brown signed SB100, a bill that commits California to 100% carbon-free electricity by 2045. SB100 is a large step, showing the world that California—the fifth largest economy in the world—is committed to both economic growth and emissions reduction.
The summit focused on five challenge areas, Healthy Energy Systems, Inclusive Economic Growth, Sustainable Communities, Land and Ocean Stewardship, and Transformative Climate Investments. Climate advocates who have dedicated their lives to this field, such as Jane Goodall, Michael Bloomberg, and Al Gore spoke on all these topics, leading to the creation of over 500 climate action commitments during the week long summit. These commitments were made by cities, companies, investors, civil society organizations, and regions globally.
The Summit was a call to action to all leaders across the world, from those who are working tirelessly to mitigate the climate change effects, to those who have yet to make a change. This summit proved that climate actions will continue to occur locally, and worldwide, no matter who is in leadership.
Can you tell us more about your internship at the California Environmental Protection Agency?
I spent the summer interning at the executive branch of the California Environmental Protection agency working with the climate program. I was able to experience the process behind how California implements its environmental policies. It was amazing being surrounded by like minded individuals who had the same drive and ambition towards environmental action. I participated in meetings with executive members of the California Air resource board, CalRecycle and other agencies and learn how they are tackling issues around topics such as biomass burning, waste sites at risk of sea level rise, dairy digesters, and the efforts each agency is doing to reduce their greenhouse gas emissions in compliance with state emission reduction goals. I had an amazing time at the Cal EPA and really enjoyed my time being a part of the team that makes California so successful in our efforts.
Sophie at the Global Climate Action Summit in San Francisco.
In addition to your studies, you work for ReGrained. Can you tell us more about the company and your role there?
Regrained is a remarkable company that works with local craft breweries to upcycle the grains leftover from the brewing process into granola bars. By repurposing this grain we’re giving it a second life and preventing food waste. Also we use completely compostable packaging, so we’re reducing food waste, without creating more waste in the process.
In my role as a brand associate with the company, I help support community engagement events and give product demonstrations, which lets me educate consumers about the impact of their choices and how we can all try to live a more conscientious lifestyle. It's empowering to live a lifestyle reflective of your values and I love that I am able to share my values with people through this position at ReGrained.
Image: Date: Tuesday, October 9, 2018 - 10:15 Legacy: section header item: Date: Thursday, October 4, 2018 - 10:15 headline_position: Top Left headline_color_style: Normal headline_width: Long caption_color_style: Normal caption_position: Bottom Left News/Story tag(s): Student Spotlights