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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.

Spawning success for white abalone

From Kat Kerlin

Efforts to bring populations of endangered white abalone back from the brink of extinction through captive breeding appear to be working, according to scientists at the UC Davis Bodega Marine Laboratory.

In 2012, UC Davis researchers achieved the first successful captive spawning of the endangered white abalone in nearly a decade. The breeding program had about 70 abalone then. After four more successful spawning events in 2013 and 2014, there are now a few thousand animals in captivity through the program. The scientists are hopeful for even greater numbers as they gear up for another spawning season this spring.

8-month old white abalone in the laboratory (Bodega Marine Lab)

8-month old white abalone in the laboratory (Bodega Marine Lab)

“We now have enough abalone in the program where we can start thinking about testing strategies to put some back into the ocean,” said Kristin Aquilino, a postdoctoral scholar at Bodega Marine Laboratory. “We’re not where we need to be for large-scale outplanting yet. To really save the species, we’re going to need to produce even more animals each year, but we’re excited about this increase.”

The scientists credit the successful spawning to a few tweaks in their process. Over time, they have incorporated more animals into each spawning attempt, which increases the chances of getting both males and females to spawn. More sophisticated facilities also allow scientists to better control the diet of young abalone at key times of their development. For example, natural fatality rates can climb above 90 percent when abalone transition from the swimming larval stage into crawling snails. Increasing their survival even by 1 percent can mean a difference of thousands of animals.

If breeding white abalone is so difficult in a controlled environment, what chance might they have in the wild, open ocean? It helps to remember that the decline of white abalone was due to overfishing, and not habitat destruction.

“If they were successfully reproducing without us before we fished them all away, hopefully whatever they need is still out there,” Aquilino said. “Their habitat is still great, so maybe captive-bred animals can thrive in the wild even better than in the lab. But their population needs a kickstart.”

UC Davis is working with partners in southern California, including UC Santa Barbara,  Aquarium of the Pacific, Cabrillo Marine Aquarium, and the Santa Barbara Museum of Natural History Sea Center to breed captive white abalone. Efforts are funded by the National Oceanic and Atmospheric Administration.

Video: White abalone captive breeding program

More information: NOAA information page on white abalone recovery efforts

Engineering self-assembling amyloid fibers

Nature has many examples of self-assembly, and bioengineers are interested in copying or manipulating these systems to create useful new materials or devices. Amyloid proteins, for example, can self-assemble into the tangled plaques associated with Alzheimer’s disease — but similar proteins can also form very useful materials, such as spider silk, or biofilms around living cells. Researchers at UC Davis and Rice University have now come up with methods to manipulate natural proteins so that they self-assemble into amyloid fibrils. The paper is published online by the journal ACS Nano.

“These are big proteins with lots of flat surfaces suitable for functionalization, for example to grow photovoltaics or to attach to other surfaces,” said Dan Cox, a physics professor at UC Davis and coauthor on the paper. They could be used as “scaffolding” for tissue engineering, and potentially could be programmed so that other particles or proteins could be attached in specific locations or arrays. Amyloids are also tough: they can withstand boiling, attack by digestive proteins and ultraviolet radiation.

Maria Peralta, a graduate student in chemistry at UC Davis, and colleagues made the amyloid fibrils by tweaking natural “antifreeze” proteins from ryegrass and an insect, spruce budworm. These proteins allow some plants and animals to withstand very cold temperatures by preventing the growth of ice crystals, but they do not naturally self-assemble into larger structures.

Making spruce budworm antifreeze protein into amyloid fibrils. The cap structure (red) was removed and other structures adjusted so that molecules could link up as fibrils (bottom).

Making spruce budworm antifreeze protein into amyloid fibrils. The cap structure (red) was removed and other structures adjusted so that molecules could link up as fibrils (bottom).

The researchers removed cap structures from the end of the antifreeze proteins. They were then able to let them self-assemble into fibrils with predictable heights, a potential new material for bioengineering.

The project was funded by the Research Investments in Science and Engineering program, established by the UC Davis Office of Research to seed large-scale interdisciplinary research efforts on campus. In addition to Cox and Peralta, the team included Arpad Karsai, Alice Ngo, Catherine Sierra, Kai Fong, Xi Chen, Gang-yu Liu and Michael Toney in the UC Davis Department of Chemistry; N. Robert Hayre, Nima Mirzaee, Krishnakumar Ravikumar and Rajiv Singh in the Department of Physics; and Alexander Kluber at Rice University, Houston. Several authors are also affiliated with the Institute for Complex Adaptive Matter, based at UC Davis.



How to slow a flu epidemic: Stay home, watch it on TV

Encouraging people to stay home instead of going out, along with other “non-pharmaceutical interventions” such as handwashing and wearing facemasks, can limit the spread of influenza virus during an outbreak according to a new study published in the open access journal BMC Infectious Diseases.

The article by researchers at UC Davis, Arizona State University, Georgia State University and Yale University provides evidence that the novel A/H1N1 influenza outbreak that hit Mexico City in April 2009 could have been worse, but spread of the virus was reduced by people’s behavioral response of distancing themselves from each other.

In April 2009 the Mexican federal government closed public schools in Mexico City and ‘social distancing’ measures were put in place. The researchers used home television viewing in Central Mexico as an indicator of behavioral response during the 2009 A/H1N1 pandemic.

Television ratings data are consistently and widely available and “highly correlated with time spent in the home,” said UC Davis economist Michael Springborn, lead author of the study. These data provide a good indicator for the level of social interaction, because time spent watching television generally increases with time spent at home. And when people are home, they are limiting the number of contacts they make.

“We found that the behavioral response to the outbreak was initially strong but waned sooner than expected,” said Springborn. This dynamic is interpreted as a “rebound effect”. At the onset of a flu outbreak, the public responds strongly to the directed control policies. But over time, there was evidence that people began to spend less time in the confines of their homes. This happened even through the true risk had not fully waned.

“This suggests that efforts to utilize social distancing to mitigate disease spread may have a limited window of efficacy, i.e. before pent up-demand for activities outside the home takes precedence,” Springborn said.

There is historical evidence for this behavior. Observations from the 1918 influenza pandemic in Australia showed that when the perceived risk decreased the public reverted back to normal behavior.

Certain age groups and socio-economic groups responded more strongly than others. The researchers found that the increase in TV watching was more pronounced for children and wealthier groups. The authors speculate that those from poorer backgrounds may face greater difficulty in taking self-protective actions like social distancing, for example due to less flexibility with working hours. These differences between demographic groups could have public health policy implications for directing outbreak response assistance to those with lower financial means or increasing access to paid sick-leave for low-wage workers.

The findings also provide insight for selection of the duration and strength of major interventions (closing of businesses and cancelling public events) versus other forms of assistance, such as distributing masks.

The study drew on the combined disciplinary strengths of epidemiology and economics to create a new model that incorporates behavioral responses into existing models of disease spread.

Social distancing policies may be effective against pandemic influenza. However, people don’t need to wait. It is important to remember that other behaviors, such as washing hands and wearing facemasks, could contribute and should be routine in order to reduce transmission.

Adapted from a BioMed Central news release.

Engineering students host “make-a-thon” for bats

While many Americans were enjoying a holiday weekend, biomedical engineering students at UC Davis worked straight through Saturday and Sunday, Jan. 17-18, to design and prototype a medical device…for bats. The effort was the first “Make-a-thon” organized by the UC Davis Biomedical Engineering Society.

“It’s the design process on steroids,” said Anthony Passerini, associate professor of biomedical engineering and director of the department’s senior design program. “The teams were doing over two days what they normally do over two quarters. They were highly constrained by time, materials, and manufacturing techniques. It was a great learning experience and a lot of fun for everyone.”

“We are so thankful for the support of ASUCD, our College and Department, the national BMES organization, and Genentech,” said Rose Hong Truong, president of the student biomedical engineering club. “The event would not have been possible without them and the TEAM Design, Prototyping, and Fabrication Facilities.”

Over the weekend, teams of students worked on a device to take skin biopsies from wild bats to aid research into White-nose syndrome. Caused by the fungus Pseudogymnoascus destructans, White-nose syndrome is a recently recognized killer of hibernating bats that is spreading rapidly across North America, wiping out up to 90 percent of some bat colonies and up to 80 percent of the entire population of bats that hibernate in caves in the northeastern U.S.

A tri-colored bat showing signs of white-nose syndrome while hibernating in a Massachusetts cave. Credit: Jon Reichard (via US Fish & Wildlife Service)

A tri-colored bat showing signs of white-nose syndrome while hibernating in a Massachusetts cave. Credit: Jon Reichard (via US Fish & Wildlife Service)

Bats matter: they are among the most important consumers of insects that plague agricultural crops. The economic losses due to the reduction in insect suppression are estimated to be anywhere from $4 to $50 billion.

UC Davis veterinary pathologist Kevin Keel and Barbara Shock, a wildlife disease ecologist at the UC Davis School of Veterinary Medicine, first approached TEAM Facilities manager Steven Lucero to develop a skin biopsy tool for wild bats, which became the focus of the Make-a-thon.

“Our research is an attempt to find ways to mitigate the mortality of bats in affected caves. Using tissue explants as a model of infection is a powerful tool that enables us to mimic the infection on bats to better understand how we might be able to limit its growth on the skin. Any tool that makes this more efficient could help us find better ways to help bats,” Keel said.

The sixty participants of the Make-a-thon were asked to design a single tool that would minimize handling of the bat, while being highly portable and easy for one person to use. The tool needs to cut the tiny piece of skin while adhering it to a support so that it is stretched for histological purposes. A single field tool that can be used by one person and does not require a cutting board will be both simpler for biologists and faster and easier for bats.

Faculty and industry judges evaluated each design and advanced four of the most feasible projects, two from UC Davis and two from the University of Southern California (USC), to the prototyping phase of the competition. These projects were assisted by the UC Davis TEAM Facility in producing working prototypes of their designs.

After testing the designs, the team of Aaron Kho, E. Aaron Cohen, Lucas Murray, Natalya A. Shelby and Shonit Sharma of UC Davis were declared Overall Winners. Their device was inspired by a piercing gun. When tested, the prototype successfully cut through a bat wing in the laboratory. Awards for “Most Potential” and “Most Creative” went to teams from UC Davis and San Jose State University, respectively.

“It was truly remarkable seeing the diversity of designs,” said Assistant Professor Jennifer Choi, one of the faculty judges for the event. “When I spoke to the participants, they were all very excited in being able to play a significant role in further understanding this critical syndrome.”

Hands-on experiences like these are critical in inspiring students to learn, said Jerry C. Hu, assistant director of the TEAM Facilities.

“We had one team consisting only of freshmen and sophomores who learned to CAD overnight! The Make-a-thon is illustrative of TEAM’s mission to benefit education, research, and the community at large. We are excited to start manufacturing the winning prototype for researchers to use across the US before the bats come out of hibernation,” Hu said.

Contributed by Holly Ober

Hybrid “super mosquito” resistant to insecticide-treated bed nets

Interbreeding of two malaria mosquito species in the West African country of Mali has resulted in a “super mosquito” hybrid that’s resistant to insecticide-treated bed nets.

“It’s ‘super’ with respect to its ability to survive exposure to the insecticides on treated bed nets,” said medical entomologist Gregory Lanzaro of UC Davis, who led the research team.

The research, published Jan. 6 in the Proceedings of the National Academy of Sciences, “provides convincing evidence indicating that a man-made change in the environment — the introduction of insecticides — has altered the evolutionary relationship between two species, in this case a breakdown in the reproductive isolation that separates them,” said Lanzaro, who is director of the Vector Genetics Laboratory and professor in the Department of Pathology, Microbiology and Immunology in the School of Veterinary Medicine.

“What we provide in this new paper is an example of one unusual mechanism that has promoted the rapid evolution of insecticide resistance in one of the major malaria mosquito species.”

Anopheles gambiae, a major malaria vector, is interbreeding with isolated pockets of another malaria mosquito, A. coluzzii. Entomologists initially considered them as the “M and S forms” of Anopheles gambiae. They are now recognized as separate species.

"AnophelesGambiaemosquito" by James D. GathanyOriginal uploader was Kpjas at en.wikipedia - Originally from en.wikipedia; description page is/was here.The Public Health Image Library , ID#444. Licensed under Public Domain via Wikimedia Commons -

Anopheles gambiae mosquito by James D. Gathany. The Public Health Image Library , ID#444.

The insecticide resistance came as no surprise. “Growing resistance has been observed for some time,” Lanzaro said. “Recently it has reached a level at some localities in Africa where it is resulting in the failure of the nets to provide meaningful control, and it is my opinion that this will increase.”

Lanzaro credits insecticide-treated nets with saving many thousands, probably tens of thousands of lives in Mali alone. The World Health Organization’s World Malaria Report indicates that deaths from malaria worldwide have decreased by 47 percent since 2000. Much of that is attributed to the insecticide-treated bed nets.

However, it was just a matter of time for insecticide resistance to emerge, medical entomologists and epidemiologist agree. Now there’s “an urgent need to develop new and effective malaria vector control strategies,” Lanzaro said. A number of new strategies are in development, including new insecticides, biological agents — including mosquito-killing bacteria and fungi — and genetic manipulation of mosquitoes aimed at either killing them or altering their ability to transmit the malaria parasite.

First author on the paper is Laura Norris, a postdoctoral scholar in the UC Davis Department of Entomology and Nematology who was supported by a National Institutes of Health training grant awarded to Lanzaro. She has since accepted a position with the President’s Malaria Initiative in Washington, D.C.

Other co-authors include, at UC Davis, Anthony Cornel, Yoosook Lee, Bradley Main and Travis Collier; and Abdrahamane Fofana of the Malaria Research and Training Center at the University of Bamako, Mali. Three grants from the National Institutes of Health funded the research.

Lanzaro has researched mosquitos in Mali for 24 years with Cornel, who is an associate professor in the UC Davis Department of Entomology and Nematology and headquartered at the UC Kearney Agriculture and Research Center, Parlier. Both are graduate student advisors in the department, training medical entomologists of tomorrow.

Contributed by Kathy Keatley Garvey.

Unraveling root growth control network

Green shoots are a sign of spring, but growing those shoots and roots is a complicated process. Now researchers at UC Davis and the University of Massachusetts Amherst have for the first time described part of the network of genetic controls that allows a plant to grow.

Plant stems and roots are built around xylem, long, hollow cells that act both as plumbing — carrying water and minerals around the plant — and as structural material. The structural strength of xylem comes from a secondary cell wall, inside the outer cell wall, which is made either of helical fibers or of perforated sheets. This secondary cell wall is made from three molecules: cellulose and hemicellulose, which are essentially sugars, and lignin, which provides strength.

Researchers interested in making biofuels from plants would like to get the sugars out of plant material without interference from too much lignin.

UC Davis graduate student Mallorie Taylor-Teeples and postdoctoral researcher Miguel de Lucas, working with Siobhan Brady, assistant professor of plant biology at UC Davis, Sam Hazen at U. Mass Amherst and others, cloned 50 genes involved in producing cellulose, hemicellulose and lignin in the lab plant Arabidopsis and screened them for interactions with more than 460 transcription factors, or genes that turn other genes on or off.

With help from UC Davis computer scientist Ilias Tagkopoulos and colleagues at the UC Davis Genome Center, the researchers were able to construct a network showing how the different genes and transcription factors are connected to each other. The results were published online Dec. 24 by the journal Nature.

“This is the first time that such a network has been worked out at this level in a plant,” Brady said. “It helps us think about how these networks are engineered and controlled.”

Notably, the network contains a large number of “feed-forward loops,” Brady said. In an example of a feed-forward loop, transcription factor X acts on factor Y, which in turn acts on gene Z. But X can also act directly on Z. Such systems are well-known in other control networks, reducing random “noise” and allowing precise coordination of different steps without a central core regulator.

The researchers were also able to study how the system reacts to different types of environmental changes. For example depriving root cells of iron promotes lignin production, which increases iron uptake. But exposing cells to salt causes a different response in which xylem cells proliferate to increase water transport.

Understanding the network of controls that influences lignin, cellulose and hemicellulose content might eventually help plant breeders create varieties best suited for harvesting for biofuel production, Brady said.

The findings grew out of more than seven years work, based on a wide range of data from genetics and plant physiology to computer science and drawing on the resources and expertise of the UC Davis Genome Center as well as U. Mass Amherst, UC Berkeley, the Cold Spring Harbor Laboratory, the U.S. Department of Agriculture laboratory in Ithaca, New York, UC San Diego and the University of Cambridge. Funding was provided by the U.S. Department of Energy, National Institutes of Health, National Science Foundation, USDA, the Royal Society (U.K.), UC Davis and the Hellman Foundation.

More information: Seeing the wood and the trees (Nature News & Views)

Wine cork or screwcap? It depends on aging

The winter holidays have brought many occasions to celebrate with wine and notice the variety of closures now being used to seal wines. As the New Year kicks off, you may find yourself wondering which type of closure is the best and whether that choice is consistent for all wines.

Andrew Waterhouse, professor and wine chemist in the UC Davis Department Viticulture and Enology, offers some research-based advice in an article recently published in The Conversation, an online publication written by academics.

The optimal wine closure depends largely on how long that wine will be allowed to age in the bottle, he advises. Will you be drinking the wine within two years of its production or will it be held in the bottle – either in the winery or at your home – for several years to maximize the flavor?

Andrew Waterhouse's lab at UC Davis studies wine chemistry.

Andrew Waterhouse’s lab at UC Davis studies wine chemistry.

“The way a bottle is sealed will directly affect how much oxygen passes into the wine each year. That will directly affect the aging trajectory and determine when that wine will be at its “best,” writes Waterhouse.

He points out that there are three types of closures now used to seal wines: natural corks made from the bark of the cork oak tree or technical corks (made of an aggregate of natural cork particles), screw caps, and synthetic corks made from plastic.

While natural corks carry the very small (1 to 2 percent) chance of causing a moldy flavor and aroma in the wine known as “cork taint,” the natural corks have proven to be the most effective in keeping oxygen out of the bottled wine over a number of years, Waterhouse reports.

“For the regular wine you might purchase for dinner this weekend or to keep for a year or two, any of these closures are perfectly good, while the manufactured closures avoid taint,” he writes. “In fact, your choice is more a matter of preference for opening the bottle. Do you want the convenience of twisting off the cap, or do you want the ceremony of removing the cork?”

But for long aging, only natural corks have a proven record of protecting the wine from unwanted oxygen, so would be the closure of choice. Waterhouse notes that long-term evaluations of synthetic corks and screw caps are needed to accurately judge their suitability for extended aging of more than 10 years.

Contributed by Pat Bailey

2015 Butterfly hunt is on!

Not the best day for it, but Prof. Art Shapiro is once again launching his “Beer for Butterfly” challenge. Find the first live Cabbage white butterfly in Sacramento, Yolo or Solano County and Shapiro will stand you a pitcher of beer (or cash equivalent if the winner is under age or doesn’t drink).

Win a pitcher of beer for the first live Cabbage White Butterfly (Pieris rapae) collected in Sacramento, Yolo or Solano County in 2015.

Your animal must be collected OUTDOORS and turned in ALIVE at the Evolution and Ecology Department Office, 2320 Storer Hall, UC Davis, with FULL DATA (exact location and date and time of collection and your contact information, preferably e-mail). If you collect it when the office is closed, keep it alive in a refrigerator (DO NOT FREEZE!) until you can deliver it. Other species are not eligible. An EVE staff member will certify that it is alive when received and take your data. The prize is a PITCHER OF BEER, your brand, or equivalent in cash if you do not drink or are under age.

In previous years winners have been collected between Jan.1 and Feb.22. Prof. Shapiro is the sole judge.

Shapiro has been running this competition (which he almost always wins) for over 40 years now, revealing information on a changing climate as well as year-to-year changes in butterfly populations.

More: Art Shapiro’s butterfly site


New X-ray technique for surfaces

Surfaces are very interesting to material scientists. The reactions that happen at the point where inside and outside meet, and elements interact with other chemicals or radiation, are important for developing new technology for batteries, fuel cells or photovoltaic panels, for catalysts for the chemical industry, and for understanding environmental chemistry and pollution. Now researchers at UC Davis and the Advanced Light Source at the U.S. Department of Energy’s Lawrence Berkeley National Laboratory have combined two existing methods techniques to come up with a new method for studying surfaces with X-rays. This new technique is called SWAPPS, for Standing Wave Ambient Pressure Photoelectron Spectroscopy.

Using SWAPPS, scientists can probe the properties of surfaces with X-rays.

Using SWAPPS, scientists can probe the properties of surfaces with X-rays.

“SWAPPS enables us to study a host of surface chemical processes under realistic pressure conditions and for systems related to energy production, such as electrochemical cells, batteries, fuel cells and photovoltaic cells, as well as in catalysis and environmental science,” says Charles Fadley, a physicist who holds joint appointments with Berkeley Lab’s Materials Sciences Division and UC Davis, where he is a Distinguished Professor of Physics. “SWAPPS provides all the advantages of the widely used technique of X-ray photoelectron spectroscopy, including element and chemical-state sensitivity, and quantitative analysis of relative concentrations of all species present. However with SWAPPS we don’t require the usual ultrahigh vacuum, which means we can measure the interfaces between volatile liquids and solids.”

Fadley is one of three corresponding authors of a paper, with Hendrik Bluhm of the Berkeley Lab’s Chemical Sciences Division and Slavomír Nemšák, now with Germany’s Jülich Peter Grünberg Institute, describing SWAPPS in Nature Communications.

X-rays probe surfaces

In terms of energies and wavelengths, X-rays serve as excellent probes of chemical processes. Fadley’s group at ALS originally developed standing wave photoelectron spectroscopy, which uses X-rays to probe buried surfaces, while a team including Bluhm developed high ambient pressure photoelectron spectroscopy, which made it possible to use X-ray spectroscopy under pressures and humidities similar to those encountered in natural or practical environments. The new technique combines the best features of both. That means the researchers can probe the composition of surfaces and interfaces with unprecedented resolution under the conditions where batteries, fuel cells or other devices actually work.

Says Fadley, “We believe SWAPPS will deliver vital information about the structure and chemistry of liquid/vapor and liquid/solid interfaces, in particular the electrical double layer whose structure is critical to the operation of batteries, fuel cells and all of electrochemistry, but which is still not understood at a microscopic level.”

The researchers used the technique to probe an experimental system of sodium and cesium hydroxide, layered on iron oxide (hematite).

“We determined that the sodium ions are located close to the iron oxide/solution interface, while cesium ions are on average not in direct contact with the solid/liquid interface,” Bluhm says. “We also discovered that there are two different kinds of carbon species, one hydrophobic, which is located exclusively in a thin film at the liquid/vapor interface, and a hydrophilic carbonate or carboxyl that is evenly distributed throughout the liquid film.”

In their Nature Communications paper, the authors say that future time-resolved SWAPPS studies using free-electron laser or high-harmonic generation light sources would also permit, via pump-probe methods, looking at the timescales of processes at interfaces on the femtosecond time scale.

“The range of future applications and measurement scenarios for SWAPPS is enormous,” Fadley says.

In addition to Fadley, Bluhm and Nemšák, other authors of the paper describing SWAPPS were Andrey Shavorskiy, Osman Karslioglu, Ioannis Zegkinoglou, Peter Greene (UC Davis), Edward Burks (UC Davis), Arunothai Rattanachata (UC Davis), Catherine Conlon, (UC Davis) Armela Keqi (UC Davis), Farhad Salmassi, Eric Gullikson, See-Hun Yang and Kai Liu (UC Davis).

This research was primarily funded by the Department of Energy’s Office of Science. The Advanced Light Source is a DOE Office of Science User Facility.

Adapted from an original story by Lynn Yarris, LBL.

More information:

Read the original story from Lawrence Berkeley Lab

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.