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About Egghead

Egghead is a blog about research by, with or related to UC Davis. Comments on posts are welcome, as are tips and suggestions for posts. General feedback may be sent to Andy Fell. This blog is created and maintained by UC Davis University Communications, and mostly edited by Andy Fell.

Advances in electron microscopy reveal secrets of HIV and other viruses

UC Davis researchers are getting a new look at the workings of HIV and other viruses thanks to new techniques in electron microscopy developed on campus.

The envelope (or Env) protein of HIV is a key target for vaccine makers: it is a key component in RV144, an experimental vaccine that is so far the only candidate to show promise in clinical trials. Also called gp120, the Env protein associates with another protein called gp41 and three gp120/gp41 units associate to form the final trimeric structure. The gp120 trimer is the machine that allows HIV to enter and attack host cells.

Professor R. Holland Cheng’s laboratory at UC Davis has previously shown how the gp120 trimer can change its conformation like an opening flower. The new study, published in Nature Scientific Reports Nov. 14, shows that a variable loop, V2, is located at the bottom of the trimer where it helps to hold gp41 in place — and not at the top of the structure, as previously thought.

New visualization of the V2 variable loop of the HIV Env protein (red) puts it at the bottom of the structure. (Cheng lab)

New visualization of the V2 variable loop of the HIV Env protein (red) puts it at the bottom of the structure. (Cheng lab)

“This challenges the existing dogma concerning the architecture of HIV Env immunogen,” Cheng said.

Making a vaccine against HIV has always been difficult, at least partly because the proteins on the surface of the virus change so rapidly. Better understanding the structure of the gp120/Env trimer could help in finding less-variable areas of these proteins, not usually exposed to the immune system, which might be targets for a vaccine.

Understanding viral entry

A second pair of back-to-back papers from Cheng’s lab uses new techniques in electron microscopy to probe how some common viruses hijack normal cellular processes to enter cells.

Cheng’s lab has pioneered techniques in cryoelectron microscopy. Traditionally electron microscopy has relied on coating or impregnating samples with heavy metal elements. Cryoelectron microscopy uses extremely low temperatures to freeze biological structures in place instead.

By taking multiple images from slightly different angles and reconstructing them with computers, Cheng has been able to produce three-dimensional images of viruses and virus proteins and particularly, virus-infected cells.

However, because of the way electrons are scattered from samples, cryoelectron microscopes can only use a limited range of angles, creating a “missing wedge” in imaging infected cells. In one of the papers recently published in the journal PLOS One, Lassi Paavolainen and colleagues present a new statistical technique to reconstruct this missing data with no prior knowledge of the sample.

In the companion paper, Pan Soonsawad and colleagues applied the new technique to study the vesicles, or small bubbles that form inside cells when a picornavirus enters. The picornaviruses are a large group that includes the viruses that cause colds, gut infections, polio, hepatitis A and the recent outbreaks of contagious hand-foot-mouth disease (HFMD) spread in infants and children of younger age in U.S. this summer.

Picornaviruses get into cells by getting themselves dragged into an endosome, or pouched-off bubble from the cell’s surface inside the cell. Then they exit the endosome and replicate their genetic material, RNA, in the cytoplasm of the host cells.

The new work shows that the endosomes are lined with host proteins called integrins, which are found in cell membranes. When integrins come close together in a membrane, they send signals into the cell. Viruses take advantage of this behavior, Cheng said. Attaching itself to a cell, the virus gathers integrins towards itself, triggering formation of an endosome.

“This virus collects integrins into a pattern so it can be ‘swallowed’ by the host cells,” Cheng said.

Once inside, the new images show the endosomes breaking up as the viruses release their genetic material into the cell, leading to massive virus replication.

Despite the illness they cause, Cheng finds the viruses have their own charm.

“The virus is beautiful, because it has its own geometry that can be reused and redesigned for the benefit of human being,” he said.

Indeed, Cheng’s laboratory has patented technology that makes use of self-assembling proteins from the coat of Hepatitis E virus, including using them to deliver drugs or vaccines or to target breast cancer.

Coauthors on the Nature Science Reports paper were Carlos G. Moscoso, Li Xing, Jinwen Hui, Jeffrey Hu, Mohammad Baikoghli Kalkhoran, Onur M. Yenigun at UC Davis; Yide Sun, Carlo Zambonelli, Susan W. Barnett, and Indresh K. Srivastava at Novartis Vaccines and Diagnostics Inc., Cambridge, Mass.; Loïc Martin, Commissariat à l’énergie atomique et aux énergies alternatives, Gif-sur-Yvette, France; Lassi Paavolainen and Anders Vahlne, Karolinska Institute, Stockholm, Sweden.

The PLOS One papers include coauthors from University of Jyvaskyla, Finland; Tampere University of Technology, Tampere, Finland; and Mahidol University, Bangkok, Thailand.

Diamonds and other treasures found in Sutter’s Mill meteorite

By Kat Kerlin

Researchers digging deeper into the origins of the Sutter’s Mill meteorite, which exploded over California’s Gold Country in 2012, have found diamonds and other “treasures” that provide important new insight into the early days of our solar system. They report their results in 13 papers in the November issue of Meteoritics & Planetary Science.

UC Davis scientists Akane Yamakawa and Qing-Zhu Yin in the Department of Earth and Planetary Sciences studied the different forms of the element chromium, called isotopes. They found that at least five different stellar sources composed of mixtures of 54-chromium-rich and -poor materials must have contributed matter to the nascent solar system four and half billion years ago. Some of these materials remained in the Sutter’s Mill meteorite.

Composite photo of the Sutter's Mill meteorite

Composite photo of the Sutter’s Mill meteorite fall.

“The formation of the solar system did not fully erase and homogenize these signatures, and Sutter’s Mill provides the clearest record yet,” said Yin, who co-led the Sutter’s Mill Meteorite Consortium with Peter Jenniskens of NASA Ames and the SETI Institute.

In primitive meteorites like Sutter’s Mill, some grains survive from what existed in the cloud of gas, dust and ices that formed the solar system. In Sutter’s Mill, the liquid water appears to have destroyed the silicate type of these, according to Xuchao Zhao of the Chinese Academy of Sciences, working with NASA and UC Davis colleagues.

Researchers in the consortium also found two, 10-micron diamond grains in the meteorite. Though too small to sparkle in a ring, they were larger than the nanometer-sized diamonds commonly found in such meteorites. Nanodiamonds are thought to originate in the atmospheres of stars. The larger diamonds found in Sutter’s Mill may have had another origin closer to home.

“We suspect that these diamonds are so-called xenoliths,” said Yoko Kebukawa, recently of Hokkaido University, Japan. “Bits and pieces that originated in the interior of other much larger parent bodies.”

Fragments of the Sutter's Mill meteorite (NASA photo).

Fragments of the Sutter’s Mill meteorite (NASA photo).

The Sutter’s Mill meteorite fell just 60 miles from the UC Davis main campus. Scientists from UC Davis, including Yin, immediately traveled to the site with students and colleagues looking for specimens and reaching out to the public to provide meteorite donation for science.

Yin confirmed that the main mass was carbonaceous chondrite – one of the rarest types to hit the Earth and containing cosmic dust and presolar materials that helped form the planets of the solar system. The meteorite’s main mass was X-rayed by CT scan at UC Davis, and the university acquired a portion of this mass.

Nobel winner headlines math/biology workshop

2013 Nobel laureate Michael Levitt of Stanford University will headline a one-day workshop on mathematics and biology to be held at UC Davis Nov. 22. Biology and Mathematics in the Bay Area aims at “creating a fairly informal atmosphere to explore the role of mathematics in biology,” according to the advance flyer. “Our goal is to encourage dialogue between researchers and students from different disciplines in an atmosphere that promotes the open exchange of ideas and viewpoints.”

Also speaking: Ileana Streinu at Smith College; Sean Mooney, Buck Institute; Sharon Aviran and Steve Kowalczykowski, UC Davis.

The meeting is free, but advance registration is required by Monday, Nov. 17. More information including registration is available at http://bambameeting.org/

Stress increases sociality in zebra finches

Stress in early life affects social behavior in adult zebra finches.

Stress in early life affects social behavior in adult zebra finches.

A new study shows that young birds raised under stressful conditions leave home earlier and develop a wider social network.

The paper co-authored by Damien Farine, now a post-doctoral researcher at the University of California, Davis, anthropology department, Neeltje Boogert, University of St Andrews, and Karen Spencer, Oxford University, was published in Biology Letters Wednesday, Oct. 29.

The researchers found that zebra finch chicks stressed during early development showed more independence from their parents, associated more randomly with other members of their flock and were less choosy about the birds they fed alongside.

“Stress is a possible mechanism to allow birds to try alternative strategies,” Farine said. “If you get a lot of this stress happening you may see them doing behaviors they have done before including widespread dispersals. When we see birds popping up in places they’ve not been before it might have something to do with stressful development. This could thus have major implications for maintaining locally-adapted behaviors and genetic structure across different sub-populations.”

Wild birds secrete a stress hormone when faced with food scarcity, predators or competition. The researchers artificially increased stress hormone levels in zebra finch chicks and tested how this affected their foraging behavior. The birds’ were monitored in aviaries where the stressed chicks and their families could visit bird feeders at any time and with any other birds. Each bird was fitted with a chip that recorded each time a bird visited one of the feeders over the course of five weeks.

For the full study go to http://rsbl.royalsocietypublishing.org/lookup/doi/10.1098/rsbl.2014.0561.

Follow Damien Farine on Twitter at @DamienFarine.

Contributed by Jeffrey Day.

UC Davis, Livermore announce graduate mentorship program awards

Contributed by AJ Cheline

Since 1963, UC Davis and Lawrence Livermore National Laboratory (LLNL) scientists and engineers have conducted joint interdisciplinary research that leverage the strengths of both institutions to address a variety of critical societal problems. Over the last year, leaders from LLNL and UC Davis have been working together to develop mechanisms that reinvigorate and deepen the partnerships between the institutions. Several joint faculty and lab researcher workshops have taken place over the last few months to identify and develop new topical areas of common interests. A number of joint grant proposals to federal funding agencies have been submitted and work is ongoing to identify funding mechanisms that facilitate additional collaborations.

As a component of this initiative, a Joint UCD-LLNL Graduate Mentorship Award program has been established. This program was created to provide a unique opportunity for graduate students to experience the complimentary research environment of both a leading university and a national laboratory during their PhD studies. The Mentorship Awards provide funding for up to three years of financial support for the graduate student. Graduate students will engage in research activities at both Livermore and Davis campuses under the joint supervision of the UC Davis faculty mentor and the LLNL staff scientist or engineer.

A Call for Proposals was issued through the UC Davis Office of Research, eliciting 25 submissions. Proposals were reviewed by independent peer review, following a process coordinated by LLNL and UC Davis. The quality of proposals was viewed as being uniformly high, with the following projects selected to receive funding in this first round:

Efficient Simulations for a Large-Scale Model of Cardiac Rhythms
UC Davis Co-Principal Investigator: Timothy Lewis, Professor of Mathematics
LLNL Co-Principal Investigator: David Richards

Engineered Nanostructure for Regulation of Cellular Signaling Cascades
UC Davis Co-Principal Investigator: Gang-yu Liu, Professor of Chemistry
LLNL Co-Principal Investigator: Ted Laurence

Ultralow Density Metal Foams for High Energy Density and Advanced Materials Research
UC Davis Co-Principal Investigator: Kai Liu, Professor of Physics
LLNL Co-Principal Investigator: Jeff Colvin

Rare Event Detection: Neutrinos and Dark Matter
UC Davis Co-Principal Investigator: Robert Svoboda, Professor of Physics
LLNL Co-Principal Investigator: Adam Bernstein

Funding for this program was provided by the University Relations and Science Education Group, LLNL, the UC Office of the President Laboratory Management Office, and UC Davis Office of Research.

Three students win EPA fellowships

Three UC Davis graduate students are among 105 to receive Science To Achieve Results (STAR) fellowships from the Environmental Protection Agency. The STAR fellows will receive a maximum funding of $42,000 a year for up to two years for doctoral students.

The UC Davis recipients and their projects are: Rachel Wigginton, “Predicting Return of Ecosystem Services Based on Impacts of Invasive Ecosystem Engineers;” Matthew Whalen, “Biodiversity of native and invasive suspension feeders affects water quality and potential for harmful algal blooms” and Kelly Gravuer, “Maintaining ecosystem function under climate change: Understanding and managing plant-soil microbe community dynamics.” All three are doctoral students.

“These fellowships are helping our next generation of scientists and engineers earning advanced degrees in environmental sciences conduct cutting edge research,” said Lek Kadeli, Acting Assistant Administrator for EPA’s Office of Research and Development in a news release. “Through this support, EPA is ensuring that the United States will have the scientific knowledge to meet future environmental challenges, which will strengthen our nation’s economy and security, while better protecting our health and environment in addition to combating climate change.”

More information about the EPA STAR Fellowship program. Wigginton also blogs at Sweet Tea, Science and is on Twitter at @RachelWigginton. Whalen tweets as @killerwhalen13.

Icelandic volcano sits on massive magma hot spot

By Kat Kerlin

Spectacular eruptions at Bárðarbunga volcano in central Iceland have been spewing lava continuously since Aug. 31. Massive amounts of erupting lava are connected to the destruction of supercontinents and dramatic changes in climate and ecosystems.

New research from UC Davis and Aarhus University in Denmark shows that high mantle temperatures miles beneath the Earth’s surface are essential for generating such large amounts of magma. In fact, the scientists found that the Bárðarbunga volcano lies directly above the hottest portion of the North Atlantic mantle plume.

The study, published online Oct. 5 and appearing in the November issue of Nature Geoscience, comes from Charles Lesher, professor of Earth and Planetary Science at UC Davis and a visiting professor at Aarhus University, and his former PhD student, Eric Brown, now a post-doctoral scholar at Aarhus University.

“From time to time the Earth’s mantle belches out huge quantities of magma on a scale unlike anything witnessed in historic times,” Lesher said. “These events provide unique windows into the internal working of our planet.”

Such fiery events have produced large igneous provinces throughout Earth’s history. They are often attributed to upwelling of hot, deeply sourced mantle material, or “mantle plumes.”

Recent models have dismissed the role of mantle plumes in the formation of large igneous provinces, ascribing their origin instead to chemical anomalies in the shallow mantle.

Holuhraun fissure eruption on the flanks of the Bárðarbunga volcano in central Iceland on Oct. 4, 2014, showing the development of a lava lake in the foreground. Vapor clouds over the lava lake are caused by degassing of volatile-rich basaltic magma. (Photo: Morten S. Riishuus, Nordic Volcanological Institute)

Holuhraun fissure eruption on the flanks of the Bárðarbunga volcano in central Iceland on Oct. 4, 2014, showing the development of a lava lake in the foreground. Vapor clouds over the lava lake are caused by degassing of volatile-rich basaltic magma. (Photo: Morten S. Riishuus, Nordic Volcanological Institute)

Based on the volcanic record in and around Iceland over the last 56 million years and numerical modeling, Brown and Lesher show that high mantle temperatures are essential for generating the large magma volumes that gave rise to the North Atlantic large igneous provinces bordering Greenland and northern Europe.

Their findings further substantiate the critical role of mantle plumes in forming large igneous provinces.

“Our work offers new tools to constrain the physical and chemical conditions in the mantle responsible for large igneous provinces,” Brown said. “There’s little doubt that the mantle is composed of different types of chemical compounds, but this is not the dominant factor. Rather, locally high mantle temperatures are the key ingredient.”

The research was supported by grants from the US National Science Foundation and by the Niels Bohr Professorship funded by Danish National Research Foundation.

Read the full study at http://www.nature.com/ngeo/journal/vaop/ncurrent/full/ngeo2264.html.

Video: Lava Fountains from Bardarbunga Volcano Holuhraun Fissure Eruption viewed by Helicopter

Bee/orchid evolution wins Packard Fellowship

Santiago Ramirez, an assistant professor in the Department of Evolution and Ecology at the UC Davis College of Biological Sciences, has been awarded a Packard Fellowship in Science and Engineering from the David and Lucille Packard Foundation. Ramirez is one of 18 scientists nationwide to receive the prestigious fellowship, worth $875,000 over five years, this year.

The fellowships are intended to give early-career scientists the freedom and flexibility to “think big” and explore new ideas and approaches.

Ramirez’ research focuses on how species adapt to each other as they evolve. Evolutionary biologists have long recognized that interactions between species play a central role in creating biological diversity. However, exactly how ecological pressures and genetics combine so that species co-evolve and adapt to each other is not well understood.

Ramirez’s research uses approaches from genetics, ecology and physiology to investigate bees and orchids have evolved together and adapted to each other. His research team is studying a group of bees called the orchid bees. This particular group of bees visits orchids — as well as other plant sources — to collect floral scents that the males present to females during courtship display. The orchids have evolved such degree of specialization to attract male bees that the plants exclusively depend on scent-seeking males for pollination.

Orchid bees and the plants they visit are highly dependent on each other.

Orchid bees and the plants they visit are highly dependent on each other.

Biologists have been puzzling over pollination for a long time: Charles Darwin and Alfred Russell Wallace worked on the problem, proposing that flowers and pollinators engaged in a race that resulted in deeper flowers and pollinators with longer noses. In fact, more than 80 percent of the world’s flowering plants depend on insects for pollination.

Previous recipients of Packard Fellowships at UC Davis are Professor Matthew Augustine, Department of Chemistry, and Professor Matthew Franklin, Department of Computer Science.

New sequencing reveals genetic history of tomatoes

By Roger Chetelat

This week, an international team of researchers, led by the Chinese Academy of Agricultural Sciences in Beijing, is publishing in the journal Nature Genetics a brief genomic history of tomato breeding, based on sequencing of 360 varieties of the tomato plant.

The C.M. Rick Tomato Genetics Resource Center here at UC Davis played an important role in this study by providing seed of both cultivated tomato varieties and related wild species.

Domestic tomatoes (left) and three wild relatives. S. pennellii is on the far right.

Domestic tomatoes (left) and three wild relatives.

This study, which builds on the first tomato genome sequence completed just two years ago, shows in great detail how the processes of early domestication and modern breeding influenced the genetic makeup of cultivated tomatoes. (UC Davis researchers also took part in an effort to sequence the genome of a wild relative of the cultivated tomato.)

Analysis of the genome sequences of these 360 varieties and wild strains shows which regions of the genome were under selection during domestication and breeding. The study identified two independent sets of genes responsible for making the fruit of modern commercial tomatoes 100 times larger than their wild ancestors.

An important finding is that specific regions of the tomato genome were unintentionally depleted in genetic variation: for example, in DNA around genes conferring larger fruit size or genes for resistance to diseases afflicting tomato plants.

These stretches of genetic uniformity illustrate the need to increase overall genetic diversity in modern varieties and highlight the important role that the Rick Tomato Genetics Resource Center and similar collections play in housing much of the genetic variability that will be critical for future breeding and research on tomato.

Plant geneticist Roger Chetelat directs the C.M. Rick Tomato Genetics Resource Center at UC Davis.

Medicine Nobel: How the brain makes sense of place

The 2014 Nobel Prize in Physiology or Medicine has been awarded to three neuroscientists, John O’Keefe, May-Britt Moser and Edvard I. Moser, for their discoveries of brain cells that allow us to make sense of place and location and navigate our environment.

In 1971, O’Keefe, then working at University College London, identified “place cells” in an area of the brain called the hippocampus. In rats, specific place cells activated when a rat was in a specific location, making up a map of the room inside the rat’s brain.

More than 30 years later, the Mosers discovered “grid cells,” that allow our brains to create coordinates and navigate between points.

Arne Ekstrom, associate professor at the UC Davis Center for Neuroscience, is building on the work of O’Keefe and the Mosers to understand how the brain can navigate a real or virtual environment.

“It is incredibly exciting that the Nobel committee has chosen to recognize and honor the seminal work of John O’Keefe and Edvard and May-Brit Moser,” Ekstrom said in an email.  “Their work has completely changed our perspective on the interface between brain and behavior, providing a critical and previously non-existent link between the activity of individual neurons and higher order cognition.”

Their work demonstrates that changes in the activity of neurons in the hippocampus and entorhinal cortex underlie the ability to spatially navigate and remember information regarding where we are, Ekstrom said.  Dr. O’Keefe’s groundbreaking work in the 70s  ushered in decades of high-impact work elucidating how these cells change their firing pattern due to changes in spatial geometry, vestibular cues, and visual cues.  In this way, place cells provide not just a code for navigation but for memory more generally. His work has also influenced our understanding of the human brain, where the existence of place cells have been confirmed in rare neurosurgical patients who explore virtual reality while undergoing brain recordings, by suggesting that place cells may be one of many different cellular mechanisms for coding the details of memories.

The Mosers’ work has similarly been highly influential in our understanding of navigation by suggesting that neurons in the entorhinal cortex code for spatial environments by firing in a regular, grid-like fashion as a rat explores a spatial environment.  These cells differ, though, in several important ways from the place cells described by O’Keefe, in that they are less sensitive to changes in spatial geometry and provide a more detailed “metric” of space than place cells do.  Recent work has also confirmed the existence of grid-cells in human neurosurgical patients; their integration into a larger memory system in humans is just beginning to be explored, including by work here at UC-Davis.

More information:

– Arne Ekstrom’s Human Spatial Cognition Lab

New York Times profile of the winners