Lawrence Livermore National Laboratory

LLNL researchers are working on a chlamydia vaccine. Image courtesy of National Cancer Institute.

Lab team wins National Institutes of Health two-year grant to develop chlamydia vaccine  

September 14, 2016

Lawrence Livermore National Laboratory, with UC Irvine and Synthetic Genomics, won a two-year $485,000 grant from the National Institutes of Health to explore new ways to develop a chlamydia vaccine.

The team's project, "Synthetic Generation of a chlamydia Vaccine," uses bioengineering to formulate a major outer membrane protein (MOMP) vaccine. This protein has proved effective in preventing the disease in mice and had promising results in non-human primate vaccine studies.

Chlamydia trachomatis is the most common bacterial sexually transmitted infection worldwide, with more than 90 million new cases of the infection each year. Treatment is available. However, antibiotics do not prevent reoccurrences. If the infection is left untreated in women, chlamydia can lead to infertility, ectopic pregnancy and preterm birth, and in newborns conjunctivitis and pneumonia.

While studies have shown MOMP significantly protects against the infection and disease, it has been extremely difficult to produce this type of vaccine because of the protein's complex structure. The immune system depends on the amino acids in the protein to fold together correctly, otherwise it cannot create the antibodies and immune cells needed to protect the body.

Photo showing  (left to right) Brad Hart, director of Lawrence Livermore National Laboratory's Forensic Science Center, biochemist Glendon Parker and chemist Deon Anex analyzing hair samples using protein markers from the hair. Photo by Julie Russell/LLNL.

LLNL-led team develops forensic method to identify people using human hair proteins  

September 7, 2016

In an important breakthrough for the forensic science community, researchers have developed the first-ever biological identification method that exploits the information encoded in proteins of human hair.

Scientists from Lawrence Livermore National Laboratory (LLNL) and a Utah startup company have developed the groundbreaking technique, providing a second science-based, statistically validated way to identify people and link individuals to evidence in addition to DNA profiling.

The new protein identification technique will offer another tool to law enforcement authorities for crime scene investigations and archaeologists, as the method has been able to detect protein in human hair more than 250 years old.

Once the method is optimized, the researchers believe they could use protein markers from a small number of human hairs, possibly as little as one, to distinguish an individual among the world's population.

"We are in a very similar place with protein-based identification to where DNA profiling was during the early days of its development," said LLNL chemist Brad Hart, the director of the Lab's Forensic Science Center and co-author of a paper detailing the work.

Photo showing Ryder Bay near Rothera Research Station, Adelaide Island, Antarctica.

Scientists identify enzymes that create a highly toxic form of mercury in Antarctic sea ice  

August 31, 2016

Researchers from Lawrence Livermore National Laboratory (LLNL) assisted a team from the University of Melbourne (link is external) in discovering how methylmercury enters the Antarctic sea and bioaccumulates in the marine food web.

LLNL scientists Michael Thelen and Adam Zemla performed protein sequence analysis and structural modeling to predict key proteins involved in mercury methylation.

Thelen explained: "We examined the sequence data obtained from DNA samples collected in sea ice and other Southern ocean environments. A candidate sequence for a mercury methylation enzyme was found in a bacterial strain of the genus Nitrospina. Then Adam used computational tools he developed at the Lab to predict the structure and show in an elegant model how the active site of the enzyme would react with mercury."

Mercury (Hg) created from volcanoes and human activity such as burning fossil fuels circulates in the atmosphere then deposits onto sea ice. The marine nitrite-oxidizing bacterium Nitrospina, may convert Hg to methylmercury (MeHg), which is released into the Southern Ocean, where it enters the marine food web. Scientists are concerned that MeHg stored in the fatty tissues of fish would contain more mercury than humans can handle and could be a public health concern in the future.

Photo showing researchers Eric Meshot, left, and Ngoc Bui evaluate the uniformity of a carbon nanotube array covering the entire area of a 4-inch wafer. Photos by Julie Rusell/LLNL.

'Second skin' uniform protects soldiers from biological and chemical agents in the field  

August 3, 2016

In work that aims to protect soldiers from biological and chemical threats, a team of Lawrence Livermore National Laboratory scientists has created a material that is highly breathable yet protective from biological agents.

This material is the first key component of futuristic smart uniforms that also will respond to and protect from environmental chemical hazards. The research appears in the July 27 edition of the journal, Advanced Materials.

High breathability is a critical requirement for protective clothing to prevent heat-stress and exhaustion when military personnel are engaged in missions in contaminated environments. Current protective military uniforms are based on heavyweight full-barrier protection or permeable adsorptive protective garments that cannot meet the critical demand of simultaneous high comfort and protection, and provide a passive rather than active response to an environmental threat.

The LLNL team fabricated flexible polymeric membranes with aligned carbon nanotube (CNT) channels as moisture conductive pores. The size of these pores (less than 5 nanometers, nm) is 5,000 times smaller than the width of a human hair.

Photo showing principal investigator Elizabeth Wheeler, Heather Enright  and lead biologist Kris Kulp. Photo by Julie Russell/LLNL.

Lab team measures peripheral nervous system activity with microchip-based platform  

July 26, 2016

For the first time, Lawrence Livermore National Laboratory (LLNL) researchers have successfully incorporated adult human peripheral nervous system (PNS) cells on a microelectrode platform for long-term testing of chemical and toxic effects on cell health and function.

The study, part of a project known as iCHIP (in-vitro Chip-Based Human Investigational Platform), was recently published online in the journal Analyst. The paper describes the integration of primary human dorsal root ganglia (DRG) cells and glial cells onto a microfluidics chip with embedded electrodes, and the successful testing of several chemicals on the living cells over a period of up to 23 days.

Ultimately, scientists say the research will provide a non-invasive testing platform outside the human body that will predict human exposure to drugs and toxins more accurately than animal studies.

"It's a platform for testing low-level chronic exposure to chemicals, for therapeutic drug screening and testing of environmental contaminants in cases where we can't test directly in humans," said the paper's lead author and LLNL scientist, Heather Enright. "This is a way to get human-relevant data without using animals; especially since those results don't always extrapolate to humans."

LLNL chemist Sarah Baker holds a gas chromatography vial used to measure the amount of methanol produced by the enzyme-embedded polymer. Photo by George Kitrinos/LLNL.

3-D printed polymer turns methane to methanol  

June 15, 2016

Lawrence Livermore National Laboratory scientists have combined biology and 3-D printing to create the first reactor that can continuously produce methanol from methane at room temperature and pressure.

The team removed enzymes from methanotrophs, bacteria that eat methane, and mixed them with polymers that they printed or molded into innovative reactors.

The research, which could lead to more efficient conversion of methane to energy production, appears in the June 15 edition of Nature Communications.

"Remarkably, the enzymes retain up to 100 percent activity in the polymer," said Sarah Baker, LLNL chemist and project lead. "The printed enzyme-embedded polymer is highly flexible for future development and should be useful in a wide range of applications, especially those involving gas-liquid reactions."

Researchers use a nontoxic aerosol tracker developed at LLNL to study how airborne biological agents might disperse through the New York City subway system.

LLNL supports NYC subway biodefense test  

June 9, 2016

Lawrence Livermore National Lab (LLNL) researchers took to the New York City subway system May 9-13 to help study how a surrogate for a biological agent, such as anthrax, might disperse throughout the nation's largest rapid transit system as a result of a terrorist attack or an accidental release.

As part of a multi-agency test sponsored by the Department of Homeland Security Science and Technology Directorate, led by MIT Lincoln Laboratory with assistance from Argonne National Laboratory, a LLNL field team spearheaded by Elizabeth Wheeler supervised the release of a harmless DNA-infused aerosol in Grand Central Terminal and two other major subway hubs, and helped collect environmental samples of the particles.

The data recorded during the study will give scientists a better understanding of the spread of airborne contaminants in the subway system and provide first responders with better pre-planning strategies and risk assessment in the event of an emergency, said LLNL's Associate Program Manager Ellen Raber, who headed the overall effort.

A team of scientists and engineers at Lawrence Livermore National Laboratory is developing

'Human-on-a-chip' could replace animal testing  

June 2, 2016

Development of new prescription drugs and antidotes to toxins currently relies extensively on animal testing in the early stages of development, which is not only expensive and time consuming, it can give scientists inaccurate data about how humans will respond to such agents.

But what if researchers could predict the impacts of potentially harmful chemicals, viruses or drugs on human beings without resorting to animal or even human test subjects?

To help achieve that, a team of scientists and engineers at Lawrence Livermore National Laboratory is developing a "human-on-a-chip," a miniature external replication of the human body, integrating biology and engineering with a combination of microfluidics and multi-electrode arrays.

The project, known as iCHIP (in-vitro Chip-based Human Investigational Platform), reproduces four major biological systems vital to life: the central nervous system (brain), peripheral nervous system, the blood-brain barrier and the heart.

Lawrence Livermore scientist Nicole Collette (right) makes bone sections on the microtome tool while Deepa Murugesh (left) records data and Cristal Yee observes. Photo by Julie Russell/LLNL.

Team IDs gene involved with fracture healing  

June 1, 2016

New identification of a gene involved in the fracture healing process could lead to the development of new therapeutic treatments for difficult-to-heal injuries.

Fracture healing involves communication between bone, muscle, vasculature and the thin membrane covering the outer surface of bones (periosteum) during the fracture repair. The periosteum contains stem cells that migrate to the fracture site and differentiate into chondrocytes (cartilage-forming cells) and/or osteoblasts (bone-forming cells).

However, little is known about the interaction between the periosteum stem cells and the bone cells during fracture healing. A team of scientists from Lawrence Livermore National Laboratory, University of California, Merced and Davis, Indiana University and Regeneron Pharmaceuticals has identified the "Sostdc1" gene as a regulator of periosteum stem cells activity during fracture repair. The research appears in the April 19 edition of the journal, Bone.

The study suggests that Sostdc1 has an important role during stem cell self-renewal and differentiation, which may be useful for developing novel therapeutics for difficult-to-heal fractures.

Jiun Chang, a UC Merced graduate student working at LLNL, studies cartilage degeneration in an anterior cruciate ligament (ACL) injury in a mouse model. The research will help doctors to better treat the onset of arthritis after a high-impact injury. Photo by Julie Russell/LLNL.

Study lays groundwork for arthritis prevention  

May 19, 2016

Joint injury can lead to post-traumatic osteoarthritis (PTOA). In fact, about half of all people who rupture the anterior cruciate ligament (ACL) in their knee will develop PTOA within 10 to 20 years of the injury.

But the molecular and cellular mechanisms leading to cartilage degeneration or PTOA due to trauma are not well understood.

Recently, a team of scientists from Lawrence Livermore National Laboratory (LLNL), University of California, Davis, University of California, Merced and Regeneron Pharmaceuticals examined the whole-joint gene expression by RNA sequencing at one day and one, six and 12 weeks after injury. The team used a new, non-invasive tibial compression mouse model of PTOA that mimics ACL rupture in humans from a single high-impact injury.

The research appears in the online edition of the Journal of Orthopaedic Research .

The Lawrence Livermore Microbial Detection Array (LLMDA) will be on board the International Space Station. Image courtesy of NASA.

LLNL biodetection system bound for space  

April 28, 2016

A biological detection system developed by Lawrence Livermore National Laboratory (LLNL) scientists that has found more than a dozen applications soon will be used in tests reaching a new frontier — outer space.

The Lawrence Livermore Microbial Detection Array (LLMDA) is a versatile tool that has been employed for all kinds of studies, from analyzing the purity of infant vaccines to detecting plague in a 14th century tooth, to learning more about combat wounds from soldiers injured in Iraq and Afghanistan.

Now a team of scientists from LLNL and three NASA research centers will use the LLMDA to study microbes that are associated with astronauts and found inside the closed environment aboard the International Space Station.

Researchers from NASA's Jet Propulsion Laboratory in Pasadena; NASA's Ames Research Center in Moffett Field, California; NASA's Johnson Space Center in Houston, and LLNL have received a three-year, $1.5 million NASA grant for characterizing microbes using state-of-the-art molecular techniques.

"The aim of the project is to provide a survey of the microbial profiles inside the International Space Station and to evaluate the possibility of the presence of pathogens that could be harmful to the astronauts' health," said LLNL biologist Crystal Jaing, the project's principal investigator.

The project, called Microbial Tracking-2, is a follow-on to NASA's Microbial Tracking-1 (MT-1) that is currently sampling and studying airborne and surface-associated populations of microorganisms aboard the International Space Station. The third and final experiment in the MT-1 series was launched to the space station on April 8 on a SpaceX cargo resupply mission.

A single chain of water molecules lines the cavity inside a carbon nanotube porin, which is embedded in a lipid bilayer. Image by: Y. Zhang and Alex Noy/LLNL.

Tiny tubes move into the fast lane  

April 4, 2016

For the first time, Lawrence Livermore National Laboratory (LLNL) researchers have shown that carbon nanotubes as small as eight-tenths of a nanometer in diameter can transport protons faster than bulk water, by an order of magnitude.

The research validates a 200-year old mechanism of proton transport.

A nanometer is one billionth of a meter. By comparison, the diameter of a human hair is 20,000 nanometers.

The transport rates in these nanotube pores, which form one-dimensional water wires, also exceed those of biological channels and man-made proton conductors, making carbon nanotubes the fastest known proton conductor. The research appears in the April 4 advanced online edition of the journal Nature Nanotechnology.

Practical applications include proton exchange membranes, proton-based signaling in biological systems and the emerging field of proton bioelectronics (protonics).

"The cool thing about our results is that we found that when you squeeze water into the nanotube, protons move through that water even faster than through normal (bulk) water," said Aleksandr Noy, an LLNL biophysicist and a lead author of the paper. (Bulk water is similar to what you would find in a cup of water that is much bigger than the size of a single water molecule).

In a composite of two images, cyan-colored drug molecules are shown passing through a cell membrane. Graphic by Tim Carpenter/LLNL.

Shaving time to test antidotes for nerve agents  

March 1, 2016

A simulation for drug-membrane permeability developed at LLNL increases the development speed for nerve-agent treatments.

Imagine you wanted to know how much energy it took to bike up a mountain, but couldn't finish the ride to the peak yourself. So, to get the total energy required, you and a team of friends strap energy meters to your bikes and ride the route in a relay, then add up your individual energy inputs.

LLNL researchers are currently using a similar approach, powered by the Laboratory's world-class supercomputers, to simulate the energy requirements for candidate drug molecules to permeate cell membranes — shaving weeks of compound testing by determining in advance how readily they'll enter cells to perform their activity.

"Instead of having one [drug molecule] starting from one side of the membrane, you have it starting at a hundred different points through the membrane," said Timothy Carpenter , a staff scientist in LLNL's Biochemical and Biophysical Systems Group .

At each of these points, the simulation imposes an artificial force of varying degree on the molecule to keep it in place. By measuring the degree of fluctuations and movement of the molecules at each of these positions, the program can obtain the related energy levels, which can then be stitched together to generate a progressive energy profile.

Monica Borucki, a scientist from Lawrence Livermore Lab's Biosciences and Biotechnology Division, looks at cell lines used for viral propagation.

Lab researchers hunt for clues in transmission of deadly Middle Eastern respiratory virus  

February 29, 2016

Lawrence Livermore Lab researchers have used new genetic sequencing technology and bioinformatics analysis to define how a novel and deadly respiratory virus changes when it passes from one host to another.

The Middle East Respiratory Syndrome Coronavirus (MERS-CoV), an RNA virus related to Severe Acute Respiratory Syndrome (SARS), can cause serious respiratory illness, fever, cough and shortness of breath in carriers and has killed roughly 40 percent of diagnosed patients. Since first being reported in Saudi Arabia in 2012, scientists have determined MERS likely originated in camels, but not much is known about how it is transmitted to humans or other animals.

As described in a paper published by PLOS ONE on Jan. 20, using ultra-deep sequencing and polymerase chain reaction tests, LLNL researchers obtained data from nasal samples of three camels infected with the human MERS virus. While only five mutations were detected in the virus' genome sequence, nearly 500 genetic variants were identified within the samples.

The findings, according to LLNL virologist and lead author Monica Borucki, suggest a high number of genetic mutations occur throughout the viral genome, previously undetected by consensus sequencing, making MERS readily transmittable from camels to humans, and potentially allowing it to survive in new environments.

Radiobiologist Matt Coleman displays a passive flow lateral device for biodosimetry developed at Lawrence Livermore National Laboratory. It's a single use protein detection assay similar to the medical diagnosis instrument Coleman helped develop for NASA for use in deep space. Photo by Julie Russell.

Scientist helps NASA develop medical device   

February 12, 2016

In the future, NASA astronauts journeying into deep space may give themselves a health check-up with the aid of a small medical device developed by a team of scientists, including one from LLNL.

Laboratory radiobiologist Matt Coleman  is part of the six-scientist team, including researchers from NASA's Ames Research Center, the University of California, Davis and Sandia National Laboratories/California, that has developed a small, portable medical diagnosis instrument.

The team members, who have filed for a patent for their medical device, were honored Jan. 27 with 2015 NASA Ames technology transfer awards during a ceremony at the Ames Research Center at Moffett Field.

The patent covers the development of a comprehensive in-flight medical diagnostic system in a hand-held format weighing less than one pound for human deep-space missions such as a mission to Mars, which is expected to take six months each way.

"The point of developing tools like this one is for detecting disease from long-term exposure to microgravity and ionizing radiation," Coleman said, adding that exposures from space exploration can potentially cause degenerative diseases of the bone, heart and eye, along with raising concerns about cancer.

"Since we don't fully understand the long-term impacts of space travel, there has been a push by NASA to better understand these effects."

LLNL scientists Gaby Loots (left) and Aimy Sebastian count live cells for their research tying a specific protein that has been found to inhibit prostate cancer metastasis to bone. Photo by Julie Russell/LLNL.

Protein curbs spread of prostate cancer to bone  

November 17, 2015

Scientists from Lawrence Livermore National Laboratory, in collaboration with researchers from University of California campuses at Merced and Davis, have found that a specific secreted protein inhibits prostate cancer metastasis to bone.

Their research appears in recent editions of the journals, PLOS ONE and Microarrays.

Prostate cancer is the most frequently diagnosed cancer and the second leading cause of cancer-related deaths among men in the United States. If detected at early stages the prognosis is quite favorable; however, aggressive forms of metastatic prostate cancer spread primarily to the skeleton.

Bone tumors cause great pain, promote fractures and ultimately represent the main cause of morbidity, with a 70 percent incidence documented by autopsies, according to Gabriela Loots, an LLNL biomedical scientists and an associate adjunct professor at UC Merced.

It has been hypothesized that the bone microenvironment serves as a rich "soil" by secreting factors that promote survival and propagation of cancer cells; in turn, tumors secrete factors that alter the bone microenvironment to promote metastatic colonization. Development of new therapies for the prevention and treatment of prostate cancer bone metastasis depends on understanding the dynamic reciprocal interactions between prostate cancer cells and the bone microenvironment.

This photograph of the rotifer Euchlanis shows all the internal organs. Rotifers are multicelled animals, with very few cells, less than 1,000. Lawrence Livermore researchers are working on research that would prevent rotifers from eating algal crops. Image courtesy of Microscopy UK.

Project aims to use probiotic bacteria to protect algal crops and increase ecosystem resilience  

July 21, 2015

A Lawrence Livermore team has received an additional $1 million to protect algal crops by developing "probiotic" bacteria to combat pond infestation and increase ecosystem function and resilience.

Algal biomass can be converted to advanced biofuels that offer promising alternatives to petroleum-based diesel and jet fuels. Additionally, algae can be used to make a range of other valuable bioproducts, such as industrial chemicals, biobased polymers and proteins.

Annual productivity is a key metric for algal biofuel production that, if optimized, could significantly decrease and stabilize biofuel price per gallon. Since grazers can result in a 30 percent loss in annual biomass productivity, a consistent mechanism for preventing predators will increase productivity and in turn decrease biofuel cost per gallon.

"We are only just beginning to understand that the pond microbiome is not only an indicator of health but also a tool for crop protection," said Rhona Stuart, one of the team members from LLNL. The team is led by Michael Thelen of LLNL and other participating institutions are Heliae Development, LLC, Sandia National Laboratories, UC Davis, and DOE's Joint Genome Institute. Other members of the LLNL team are Rhona Stuart and Xavier Mayali.

The goal of the project is to identify and employ "probiotic" bacteria to increase microalgal survival by two-fold when under attack by rotifers or chytrids in mass algal cultures.

LLNL biomedical scientist Celena Carrillo conducts benchtop experiments in a collaboration between the Laboratory and three other institutions that assisted Sunnyvale-based Cepheid in advancing an Ebola virus detection test for emergency use. Photo by Julie Russell.

Lawrence Livermore researchers help biomed company land FDA approval for Ebola detection  

May 28, 2015

Researchers from LLNL and three other institutions have assisted a Bay Area biomedical company in advancing its Ebola virus detection test for use.

Sunnyvale, California-based Cepheid has received an emergency use authorization from the U.S. Food and Drug Administration (FDA) to utilize its polymerase chain reaction (PCR)-based assay for diagnostic purposes.

"We received a Cepheid GeneXpert system, as well as their experimental Ebola assay cartridges, and tested them against non-Ebola bacterial and viral targets to show that the assay would only detect Ebola," said Reg Beer, LLNL's medical diagnostics initiative program leader.

The Livermore testing, which was conducted under a work for others contract, was performed by Beer and biomedical scientists Pejman Naraghi-Arani and Celena Carrillo, who ran the benchtop experiments. No live virus material was used for these reserach studies.

"This exclusivity testing supported Cepheid's request to the FDA for an emergency use authorization (EUA) with the current Ebola outbreak. Our data was included in the FDA submission," Beer said.

In their work for Cepheid, the three Lab scientists tested about 25 target organisms, including inactivated RNA from multiple strains of Ebola virus and Marburg virus.

PLS biologists James Thissen and Crystal Jaing along with researchers from Kansas State University found that the Microbial Detection Array could help identify diseases in the commercial swine industry.

Lawrence Livermore technology could help detect diseases in commercial swine industry  

May 19, 2015

Agricultural officials who seek to detect diseases affecting the commercial swine industry may gain a new ally — a biological detection system developed by Lawrence Livermore National Laboratory (LLNL) researchers.

A study by LLNL and Kansas State University scientists found that the Lawrence Livermore Microbial Detection Array (LLMDA) could help identify diseases in the commercial swine industry. Many of the diseases affecting the commercial swine industry involve complex syndromes caused by multiple pathogens, including emerging viruses and bacteria.

One pivotal advantage of the Livermore-developed LLMDA over other detection technologies is that it can detect within 24 hours any bacteria or virus that has been previously sequenced.

Currently, polymerase chain reaction (PCR) assays represent one technology widely used for pathogen detection, but typically only a handful of microorganisms can be identified in a single test. "The LLMDA can identify co-infections from a single sample," said LLNL biologist Crystal Jaing , who oversees LLNL's microbial detection array collaborations. "A PCR test cannot. The array also can identify co-infections faster and cheaper than DNA sequencing."

Graphic depicts an experiment at SLAC that revealed how a protein from photosynthetic bacteria changes shape in response to light.

X-ray laser acts as tool to track life's chemistry  

December 5, 2014

An international research team that includes researchers from Lawrence Livermore National Laboratory has captured the highest-resolution protein snapshots ever taken with an X-ray laser, revealing how a key protein in a photosynthetic bacterium changes shape when hit by light.

Image courtesy of SLAC National Accelerator Laboratory.

Graphic depicting a cerebral aneurysm.

A tool to better screen and treat aneurysm patients  

May 29, 2014

New research by an international consortium, including a researcher from Lawrence Livermore National Laboratory, may help physicians better understand the chronological development of a brain aneurysm.

LLNL biologist Crystal Jaing and computer scientist Kevin McLoughlin analyze an image from the Lawrence Livermore Microbial Detection Array.

Livermore Lab's microbial detection array detects plague in ancient human remains  

March 6, 2014

Scientists who study past pandemics, such as the 14th century Black Death that devastated much of Europe, might soon be turning to an innovative biological detection technology for some extra help.

Livermore Lab biologist Crystal Jaing prepares a Microbial Detection Array slide, the primary detection technology used in an international study of bladder cancer samples.

Association between virus, bladder cancers detected using Lawrence Livermore technology  

September 10, 2013

A Lawrence Livermore National Laboratory (LLNL)-developed biological detection technology has been employed as part of an international collaboration that has detected a virus in bladder cancers.