Category: News

Bionetix collaboration seeks novel cancer drug that targets a genetic switch

Posted on October 2, 2017

Southern Research and Bionetix Inc., a South Korea-based biotech firm, have signed a research and license agreement to develop a new anti-cancer drug that affects a key genetic switch associated with suppression and regulation of the growth of certain types of cancer.

The goal of the research is to develop a novel drug that would block, or inhibit, certain epigenetic processes linked to changes in tumor cell DNA that allow those cells to survive and begin spreading.

A new drug that inhibits these processes could also be useful against chemotherapy-resistant tumors in combination with targeted cancer therapeutics and as an adjunct therapy for cancer immunotherapies.

This collaboration is based on the extensive expertise of Birmingham-based Southern Research in the discovery of novel cancer therapeutics including promising research on the regulation of tumor growth by controlling how genes are turned on and off in the cell

Southern Research drug discovery — Southern Research boasts an extensive drug discovery infrastructure along with expertise in chemistry and biology.

“The collaborative effort with Bionetix will allow us to accelerate our exploration of an epigenetic approach that could produce life-saving anti-cancer agents as well as continue our commitment to the identification of novel therapeutics,” said Mark Suto, Ph.D., vice president of Southern Research’s Drug Discovery Division.

Doo Young Jung, CEO of Bionetix, said the teams seek to develop new epigenetic enzyme inhibitors that are more effective than existing drugs so their use can be expanded to successfully treat a broader range of cancers.

“I believe that this collaborative research program will help to expedite the development of novel inhibitors into the clinic so that we can contribute benefits to cancer patients,” he said.

‘EXPLORATORY EFFORT’

Under the Bionetix agreement, Southern Research will conduct studies to identify and optimize new inhibitors of methyl transferases as potential drug candidates. In collaboration with Bionetix, Southern Research will also define the overall development strategy for the new compounds.

“What we are looking at in this exploratory effort is a wide range of specific genes and biomarkers,” Suto added. “That will help us identify the types of tumors that should be targeted and which patients would be most likely to benefit from the treatment based on this epigenetic approach.”

Southern Research Suto — Mark Suto is Southern Research’s vice president of Drug Discovery.

Southern Research and Bionetix plan to complete the collaborative research program and begin preclinical and clinical development programs by early 2019.

As part of the arrangement, Bionetix can exercise an option to acquire the global exclusive commercialization rights for the optimized inhibitors and the application technologies, and will develop them further independently.

The deal with Bionetix represents the first licensing agreement signed by Southern Research in a decade. Bionetix, based in Suwon, South Korea, is a start-up company backed by venture capital investments.

Bionetix is providing research support for Southern Research, which will provide its extensive expertise in biology and chemistry to move the drug discovery research program forward.

Bionetix is devoted to the development of new small molecule drugs by efficient translation of innovative basic sciences developed by public research institutes. The firm is working with various public research organizations, including Southern Research’s Drug Discovery division, the Korea Research Institute of Chemical Technology, and the Ajou University of Korea, to develop new drugs in the opthalmalogy and oncology fields.

New drug discovery collaboration targets novel treatments against diseases

Posted on September 20, 2017

Southern Research and the University of Tennessee Health Science Center (UTHSC) have formed a partnership to advance promising research that could lead to new drugs that address unmet medical needs.

The collaborative program links the drug discovery and development expertise of Birmingham-based Southern Research with UTHSC’s four-campus research network, which was involved in sponsored programs valued at $240.5 million in fiscal year 2016.

“We believe there are a lot of synergies between the two organizations,” said Mark Suto, Ph.D., vice president of Drug Discovery for Southern Research. “UTHSC brings novel scientific insights into diseases with poor treatment options, and we have proven capabilities in drug discovery and development.

“This collaboration with talented UTHSC researchers has great potential to lead to significant discoveries,” Suto added.

Southern Research HTS — Southern Research’s drug discovery efforts are aided by a High-Throughput Screening system.

The new UTHSC/SR Collaborative Research Network (CORNET) Award in Drug Discovery and Development represents an extension of a program launched by Steven R. Goodman, Ph.D., vice chancellor for research at UTHSC in 2016.

The CORNET Awards are designed to provide seed money to support new collaborative research teams and their projects. To-date, the program has provided over $1.1 million in funding to promising university research teams.

Glen E. Palmer, Ph.D., an associate professor in the College of Pharmacy at UTHSC, has been selected to receive the first jointly funded UTHSC/SR CORNET Award. Palmer is targeting the development of an entirely new class of antifungal medications to combat a range of invasive fungal infections, which are blamed in an estimated 1.5 million deaths a year.

“I want to congratulate Dr. Glen Palmer on being our first UTHSC/SR CORNET Award recipient and a second-time CORNET awardee,” Goodman said. “The UTHSC/SR CORNET Award is focused on drug discovery and development for any human disease. We are hopeful that Dr. Palmer’s exciting work and our partnership with Southern Research will lead to a new class of medications against invasive fungal infections.”

TEAMWORK APPROACH

Under the new program, UTHSC scientists can apply for funding to advance their research. The partnership is awarding Palmer $50,000 per year for up to two years, with funding for year two dependent upon progress made in year one.

Research projects receiving funding from the UTHSC/SR CORNET Award can take advantage of the shared resources of Southern Research and UTHSC to facilitate drug discovery and development efforts aimed at any disease.

Southern Research’s established drug discovery infrastructure will play a key role in the partnership. The organization’s High-Throughput Screening (HTS) Center has a library of more than 1 million compounds and state-of-the-art robotic equipment for a wide variety of screens.

The Birmingham-based non-profit also has deep expertise in medicinal chemistry and pre-clinical drug development, along with bio-containment laboratories and other resources.

Southern Research scientists have discovered seven FDA-approved drugs used in cancer treatment and have evaluated a significant percentage of all medicines on the market.

Southern Research and UTHSC will jointly own intellectual property resulting from projects receiving support from the program. Outside partners will be sought for clinical development and commercialization when projects reach an advanced stage.

INITIAL PROJECT

Palmer’s research project, titled “Targeting the Aromatic Amino Acid Synthesis Pathway to Develop a New Class of Broad Spectrum Antimicrobial Agents,” aims to develop first-in-class broad-spectrum antimicrobial agents for the treatment of what are often fatal invasive fungal infections.

These infections are a serious and growing global health problem, with mortality rates often exceeding 50 percent for many fungal pathogens. Disturbingly, some of these pathogens are developing resistance to the antifungal drugs now in use.

“Mortality rates associated with invasive fungal infections have remained alarmingly high, as many of the antifungal drugs currently available are ineffective in treating these infections, or in some cases themselves are toxic to the patients,” Palmer said.

“Over the last few years, my lab has devised some novel approaches to discover new antimicrobial compounds. The collaborative effort between the University of Tennessee Health Science Center and Southern Research will provide a framework with the resources needed to apply these methods on a scale at which they can have a real impact,” he added.

“Additionally, it will bring the know-how and experience needed to progress the experimental therapeutics we discover towards new and improved drugs to ultimately improve the prognoses of patients with life-threatening invasive fungal infections.”

Southern Research’s HTS Center will assist Palmer in screening around 200,000 compounds for active chemical leads as part of the project. Southern Research’s Chemistry Department will play an integral role in the work after the initial active compounds are identified.

Southeast Energy Storage Symposium showcases disruptive technology

Posted on September 14, 2017

Southern Research is hosting the Southeast Energy Storage Symposium, which will offer insights from top experts and policymakers on disruptive technologies in energy storage that are poised to spark major changes for electric utilities and other industries.

The symposium, the first of its kind in the region, is designed to cover all aspects of energy storage, which encompasses a broad range of technologies that capture energy for use when it’s needed. The event is scheduled for Sept. 27 and 28 at both of Southern Research’s Birmingham campuses.

Bert Taube, Ph.D., senior principal investigator for Energy Storage in Birmingham-based Southern Research’s Energy & Environment division, said the symposium aims to comprehensively address developments taking place throughout the energy storage landscape.

Southern Research PV panels — Southern Research operates the Southeast Solar Research Center, where the performance and longevity of solar PV panels are tested.

“This symposium is gathering energy storage leaders from across the U.S. with expertise in different fields – technology, economics, policy – at a time when innovation is making these systems more capable of performing reliably on an industrial scale,” Taube said.

“It covers all facets of the topic, from the technologies and their commercialization in various industrial applications to the manufacturing, integration, operation and maintenance of large-scale energy storage systems to drive grid modernization with enhanced reliability and performance in the U.S. Southeast,” he added.

TECHNOLOGY ON DISPLAY

The symposium’s speakers and panelists include highly regarded professionals from the U.S. Department of Energy (DOE), the Pacific Northwest, Oak Ridge and Sandia National Laboratories, Southeastern utilities, manufacturers and regulators. Among the participants:

Imre Gyuk, Ph.D., director of energy storage research in the DOE’s Office of Electricity and Energy Reliability, who is considered a central figure in the developing field.
Mike Bush, manager of generation planning and development at Southern Company, where he provides leadership and strategic direction for supply side technology evaluation and integration, asset valuation, asset acquisition, project development and pre-commercial asset management for Southern Company’s retail operation companies.
Gary Brinkworth, director of enterprise research & technology innovation at Tennessee Valley Authority, where he leads the team responsible for coordinating the company’s R&D efforts.
Haresh Kamath, senior program manager for distributed energy resources at the Electric Power Research Institute (EPRI), where he manages research into the development and application of energy storage systems.
Vincent Sprenkle, Ph.D., technical group manager for the electrochemical materials and systems group at Pacific Northwest National Lab and manager of the energy storage portfolio for the Department of Energy.
Bharat Balasubramanian, Ph.D., a former R&D engineer for Mercedes-Benz who now serves as executive director of the University of Alabama’s Center for Advanced Vehicle Technologies.
Donald Baxter, CEO of Alabama Graphite and one of the premier graphite experts in the world known for his coated spherical purified graphite battery-ready program in the industry.

Southern Company’s Steve Baxley, a panelist at the event, said energy storage systems have important implications for electric utilities, potentially allowing them to smooth out demand peaks with power produced earlier from other sources, including renewables such as solar and wind.

“Today, whenever you flip a light switch on, the energy provider has to instantly match power generation to that change in demand,” said Baxley, an R&D manager who directs the Atlanta-based utility’s renewable, energy storage and distributed generation pilot projects.

“Instead of having to follow demand, we could harness this new technology to optimize generation to be more efficient – ultimately providing greater value to our customers,” he added.

Energy Storage Southern Research — Bert Taube is senior principal investigator for Energy Storage at Southern Research.

Those attending the symposium will also see technology displays and tour the Southeast Solar Research Center, a collaborative effort between Southern Research, Southern Company and its subsidiaries, and EPRI, where the performance and longevity of solar PV panels are being tested.

They’ll also see the Energy Storage Research Center, which is being developed as a platform for testing and validating technologies that could bring energy storage systems into operation at grid scale. The center will also be capable of researching industrial applications such as automotive.

Southern Research is launching the Energy Storage Research Center in collaboration with Southern Company and its Alabama Power subsidiary, DOE, Oak Ridge National Laboratory, EPRI and the State of Alabama.

CRITICAL TECHNOLOGY

Experts say energy storage systems represent a critical technology in the smart electricity grids envisioned for the future. Significantly, these systems will support the integration of renewable energy generation, helping to lower costs and cut emissions.

The energy storage market is poised for rapid growth. In 2013, the installed base of these systems was a mere 0.34 gigawatts (GW), according to the Energy Storage Association, an industry group. This year, annual installation reached 6 GW. In 2022, the figure will be over 40 GW.

Bill Grieco, Ph.D., vice president of Southern Research’s Energy & Environment division, said the organization is positioned to participate in the long-term growth of energy storage systems as they become fully integrated into electric power management.

“Our new Energy Storage Research Center will serve as an industry-wide resource to support emerging energy storage technologies,” Grieco said. “Working with a range of collaborators, we will develop joint energy storage research test projects and independently evaluate technologies to speed the development and commercialization of these systems.”

Southern Company is serving as host utility for the Southeast Energy Storage Symposium. Sponsors are CSA Group, EOS, UniEnergy Technologies, ZeroRPM, AES Energy Storage, and NEI.

Southern Research expands STEM education outreach with key hire

Posted on September 11, 2017

Southern Research announced plans to expand the scope of its longtime educational outreach efforts with the hiring of a STEM educator to direct a statewide program that aims to inspire young people to pursue careers in science and engineering, in addition to training teachers involved in these fields.

Kathryn Andrea Lanier, Ph.D., joins Birmingham-based Southern Research as its first STEM Education Outreach Director. She will design programs that will bring stimulating, hands-on learning experiences focusing on science, technology, engineering and math activities to students across Alabama.

“Since its founding more than 75 years ago, Southern Research has executed on a mission to introduce young people to science and engineering, to inspire some as a career choice, and for all to be citizens better equipped to make important decisions,” said Art Tipton, Ph.D., the non-profit organization’s president and CEO.

“Kathryn coming on board furthers that important effort, and positions Southern Research more strongly to participate in the development of the next generation of STEM professionals powering new discoveries in Alabama,” Tipton added.

Southern Research STEM — Southern Research plans to expand the scope of its longtime educational outreach efforts with the hiring of a STEM educator to direct a statewide program.

The expansion of Southern Research’s STEM education efforts is made possible by funding from the Alabama Legislature earlier this year. This support prompted the organization to further study how its STEM outreach can complement existing programs across the state and fill gaps that currently exist.

“Southern Research has been responsible for many important accomplishments, from discovering seven cancer-fighting drugs and supporting the space program to contributing to key national defense programs,” Governor Kay Ivey said.

“It’s exciting to see this unique organization expand its mission to inspire young people in Alabama today to explore opportunities in the types of 21^st Century jobs that will move our state forward,” she added.

Governor Ivey visited Southern Research’s downtown Birmingham campus on Friday, Sept. 8, where she met Lanier. She also talked with researchers including Rita Cowell, Ph.D., a neuroscientist studying Parkinson’s and other diseases; Rebecca Boohaker, Ph.D., a cancer researcher; Lindsay Miller, an associate scientist; Ken Jeffers, manager of resource recovery; and Jacques Cuneo, a materials engineer.

The governor is also addressed Southern Research employees during a short reception in the Martin Library.

FUTURE GENERATIONS

Southern Research STEM education — Kathryn Lanier is joining Southern Research as its first STEM Education Outreach Director.

Southern Research is expanding its educational outreach at a time when STEM jobs are in demand. Figures from the U.S. Bureau of Labor Statistics (BLS) show that employment in STEM occupations grew by 10.5 percent between 2009 and 2015, compared to 5.2 percent for non-STEM jobs.

Highly sought-after STEM workers also earn more than employees in other fields. The average STEM salary was $85,570 in 2015, nearly double the $45,700 average for all occupations, according to BLS data published this year.

Lanier, who holds a doctorate degree in biochemistry from the Georgia Institute of Technology, has been heavily involved in STEM outreach programs. She has conducted workshops for STEM educators, directed hands-on science activities for elementary school students, and mentored high school and college students.

Lanier has authored several scientific papers, delivered presentations at conferences, and acted as an instructor in college-level lecture and laboratory classes.

She said her new position at Southern Research aligns with her lifelong goal of inspiring future generations of scientists.

“While biochemical research is my forté, STEM education and outreach is my passion,” Lanier said. “I not only consider STEM outreach work to be a form of giving back, but I also believe regaining and promoting science and math literacy is imperative to our country’s future. I am so grateful for the opportunity to empower the many diverse communities of Alabama and stimulate the state’s STEM learning environments.

“Southern Research has all the necessary components to provide exceptional educational experiences to those across the state,” she added. “We’ll do this together, and I am honored to be part of it.”

Southern Research technology captures ‘spectacular’ eclipse imagery

Posted on August 24, 2017

Sophisticated telescopes developed by Southern Research captured unique images of the Sun’s outer atmosphere during Monday’s “Great American Eclipse,” and scientists are beginning a detailed examination of data described as “spectacular.”

The imagery was captured by two NASA high-altitude research aircraft as the total solar eclipse unfolded over the United States.

The goal of the eclipse mission, led by NASA and supported by Southern Research, was to gather visible and infrared images of the solar corona and collect extensive data on the temperature of Mercury’s surface.

“The visible and infrared data look spectacular,” said Southwest Research Institute Senior Research Scientist Amir Caspi, Ph.D., principal investigator of the project. “We’re already seeing some surprising features, and we are very excited to learn what the detailed analysis will reveal.”

Southern Research eclipse imagery — This is an infrared image of the sun captured by Southern Research-developed telescopes during the Aug. 21 total solar eclipse.

The Southern Research-developed stabilized telescopes with sensitive, high-speed, visible-light and infrared cameras flew aboard the NASA WB-57F research aircraft to observe the targets from 50,000 feet, providing a significant advantage over ground-based observations.

Birmingham-based Southern Research built the Airborne Imaging and Recording Systems (AIRS) onboard and worked with the scientific team to retrofit its DyNAMITE telescopes with solar filters and improved data recorders and operating software.

CRITICAL ROLE

Charlie Mallini, NASA’s WB-57 program manager, said he was delighted with the success of the eclipse mission and the performance of Southern Research’s technology on the flight.

“Without Southern Research the NASA’s WB-57 solar eclipse mission would not have occurred,” Mallini said. “Their diligent preparation and operation of the DyNAMITE sensor was critical to the mission’s success. They were a valuable member of NASA’s WB-57 solar eclipse mission team.”

Johanna Lewis, program manager of the AIRS/DyNAMITE system, said the mission represented an exciting moment for the Southern Research engineering team.

“Southern Research has been a proud supporter of the NASA WB-57 since 2003, and during that time we have supported hundreds of flights and data collections, but this was one of the most exciting,” Lewis said.

Southern Research not only provided the instruments to collect the unique imagery but also a key member of the high-altitude crew. Southern Research’s Don Darrow was the Sensor Equipment Operator (SEO) flying in the lead plane, so he was the first to acquire the solar eclipse in totality.

“The view of the eclipse from aboard the WB-57 was fantastic,” Darrow said. “I was able to see the eclipse from the sensors aboard the plane and then look up and see it directly with my own eyes. I had one of the best views of the eclipse on the planet. It was truly an awe inspiring flight.”

‘PHENOMENAL JOB’

Total solar eclipses are unique opportunities for scientists to study the hot atmosphere above the Sun’s visible surface. The faint light from the corona is usually overpowered by intense emissions from the Sun itself. During a total eclipse, however, the Moon blocks the glare from the bright solar disk and darkens the sky, allowing the weaker coronal emissions to be observed.

“This is the best observed eclipse ever,” said Dan Seaton, Ph.D., co-investigator of the project from the University of Colorado. “With the results from the WB-57s and complementary observations from space and other experiments on the ground we have an opportunity to answer some of the most fundamental questions about the nature of the corona.”

The eclipse also provided an opportunity to study Mercury, which is notoriously difficult to image because of its proximity to the Sun. Using infrared in near darkness through very little atmosphere, the team received data enabling it for the first time to estimate the surface temperatures over the planet’s night side.

“The pilots, instrument operators, and engineers did a phenomenal job getting us exactly the data we asked for,” Caspi said. “Achieving this quality of measurement required an enormous effort and precise timing, and everyone hit their mark exactly. I am honored to be part of such an exceptionally talented and professional team, and grateful for everyone’s dedication and hard work.”

Southern Research to play key role in low cost carbon fiber project

Posted on August 17, 2017

Southern Research is part of a team exploring clean, cost-efficient approaches of producing carbon fiber from coal and other sources.

The U.S. Department of Energy’s (DOE) Office of Energy Efficiency and Renewable Energy (EERE) recently announced that Western Research Institute (WRI) was selected for an award with DOE funding of $3,745,413 to develop low cost carbon fiber components using various resources as the feedstock, such as coal and biomass. With partner cost share included, the overall value of the project as proposed is nearly $7 million.

Southern Research’s Energy & Environment division (E&E) will participate as a subcontractor to WRI to provide renewable acrylonitrile — the key raw material needed to produce the highest quality carbon fibers — produced from biomass-derived second generation sugars.

“At Southern Research we have developed an innovative, thermocatalytic process that converts second generation sugars obtained from biomass to acrylonitrile,” said Amit Goyal, Ph.D., manager, Sustainable Chemistry and Catalysis and principal investigator for Southern Research’s E&E division.

Southern Research carbon fiber — Southern Research’s Amit Goyal, right, spearheaded the development of a process that could lead to low cost carbon fiber from biomass.

The Southern Research process produces a direct drop-in replacement for petroleum acrylonitrile that is both economically competitive and sustainable, lowering greenhouse gas (GHG) emissions by up to 40 percent.

“Ninety percent of the world’s carbon fiber production utilizes acrylonitrile as a raw material, growing at 11 to 18 percent per year. Due to the high growth rate of carbon fiber production, any reduction on GHG will be highly impactful,” Goyal said.

GAME-CHANGING APPROACH

The goal of the project with WRI is to expand the range of biomass feedstocks that the Southern Research process can use and to understand how the process is affected by impurities that change when different types of biomass and different biomass-to-sugar processes are used. Experimental data generated in this project will allow collaborators to better predict and improve the overall cost and application areas for carbon fibers.

“The Southern Research process for producing acrylonitrile from biomass-derived sugars has the promise of changing the economics and environmental footprint of this important specialty chemical,” said Bill Grieco, Ph.D., vice president of Southern Research’s E&E division.

“Making that process more robust and agnostic to biomass sugar feedstock is another important step toward commercialization of the technology,” he added.

Team members working on the project led by WRI are Ramaco Carbon LLC, Oak Ridge National Laboratory, Massachusetts Institute of Technology Grossman Advanced Materials Group, Terra Power LLC, Autodesk Inc., Advanced Carbon Products LLC, and The University of Wyoming.

The project is among 22 announced in July by DOE related to research into advanced vehicle technologies.

Southern Research targets bio-threats under BARDA contracts

Posted on August 8, 2017

Southern Research has been awarded two contracts from the Biomedical Advanced Research and Development Authority (BARDA), which is a division of the U.S. Department of Health and Human Services’ Office of the Assistant Secretary for Preparedness and Response, for nonclinical research services advancing the agency’s work to protect the U.S. against infectious disease and bio-terror threats.

The BARDA contracts have a minimum value of $45 million and a maximum value of $90 million and a base term of five years.

Southern Research, which has considerable experience in infectious disease research, has long been a leader in the evaluation of vaccine candidates and possible therapeutics for influenza and emerging biological threats.

Southern Research bio-threats — Southern Research has won two contracts from BARDA for work to protect the U.S. from infectious diseases and bio-terror threats.

“This work positions Southern Research to play a key role in protecting against potentially serious public health issues,” said Tim McGrath, vice president, Drug Development.

“We have the expertise and capabilities to accelerate the development of vaccines and therapeutics that are effective against biological threat agents.”

PORTFOLIO OF COUNTERMEASURES

BARDA’s mission includes developing medical countermeasures our nation needs to protect public health against emerging infectious diseases, pandemic influenza, and chemical, biological, radiological, and nuclear threats.

Under one of the BARDA contracts, Southern Research will develop and utilize novel animal models used in the testing of potential vaccines and therapeutics against biological threat agents.

The development of animal models is considered a key element in the evaluation of medical countermeasures for this broad range of threats because the efficacy of these products cannot be verified using traditional clinical studies.

“Southern Research is pleased to continue this relationship with BARDA and support this critically important initiative,” said Michelle Wright Valderas, director of project management and principal investigator on this contract.

The second BARDA-supported project is focused on developing the reagents and assays that would be used to support the animal model testing and later human clinical trials.

“I am excited to contribute to this important research supporting vaccine development to protect public health,” said John Farmer, a project leader responsible for immunology research at Southern Research and principal investigator on this contract.

IDIQ CONTRACTS

Task orders issued under these contracts will be funded in whole or in part with federal funds from the Department of Health and Human Services Office of the Assistant Secretary for Preparedness and Response, Biomedical Advanced Research and Development Authority, under Contract Nos. HHSO100201700017I and HHSO100201700018I.

Both are Indefinite Delivery Indefinite Quantity (IDIQ) contracts, meaning Southern Research is positioned to bid on task orders once they are issued by BARDA. All work will be conducted using quality standards consistent with Good Laboratory Practices (GLP) guidelines.

Southern Research worked previously with BARDA under a 2011 IDIQ contract to develop animal models. In addition, Southern Research has worked as a subcontractor with other organizations on BARDA contracts.

Southern Research ready to assist new hepatitis B treatment approaches

Posted on July 28, 2017

A Southern Research scientist says a new generation of antiviral therapies is urgently needed against hepatitis B, a chronic disease affecting 240 million people whose cure has proved elusive.

Raj Kalkeri, Ph.D., a project leader and subject matter expert in infectious disease for Southern Research’s Drug Development division, added that the stubborn characteristics of the hepatitis B virus (HBV) have thrown up significant hurdles slowing the discovery and development of a cure for this persistent viral infection.

“Because of its role in at least 650,000 deaths each year, hepatitis B constitutes a major international public health problem,” Kalkeri said. “HBV persistence can lead to cirrhosis, liver failure and the primary form of liver cancer, hepatocellular carcinoma. This places a major burden on health care costs.”

Southern Research hepatitis B — Raj Kalkeri, standing at right, works with a HBV team in a Southern Research laboratory.

Birmingham-based Southern Research has been active in the effort to advance new treatments by developing comprehensive hepatitis B capabilities for researchers. This includes in vitro assays to monitor different phases of the HBV life cycle, along with a mouse model for persistent HBV infection that could be useful in testing a new generation of HBV therapies.

What’s needed now, Kalkeri said, is greater cooperation within the scientific community and additional support for research that targets the infection’s most challenging aspects, including its persistence and ability to suppress an immune system response.

“Concerted efforts across academia, industry and government are needed,” he said. “Collaborations across these groups with additional research funding will facilitate better understanding of HBV persistence and the development of effective strategies to advance a functional cure.”

COMBATTING PERSISTENCE

While there is a safe and effective vaccine for hepatitis B, it fails in 5 to 15 percent of persons receiving the vaccine. Smoking, obesity, other chronic illnesses and advanced age are some of the factors associated with vaccine failure.

Current antiviral therapies can halt the progress of the infection in some patients, but they don’t wipe out all traces of the virus. That allows HBV to hide out for some time, before reappearing once therapy is completed.

Hepatitis B’s persistence, which can turn the disease into a lifelong struggle for many sufferers, is a complex phenomenon, Kalkeri said.

For starters, the human immune system has a hard time clearing out hepatitis B. It begins when T-lymphocytes, a key component of the immune system that combats microbial intruders, fail to do their job because of disruption caused by the virus.

Reversing this defective T-cell response could be helpful in the development of new hepatitis B treatments, though it’s probably not sufficient alone to play a starring role in a cure, Kalkeri said.

The major challenge with hepatitis B persistence is known as cccDNA, short for covalently closed circular DNA. This is a special DNA structure that’s deposited in the nucleus of HBV infected cells in the form of minichromosome. Its strategic location makes it a difficult target for antivirals and for the immune system.

Present in low levels, the seemingly untouchable cccDNA continues to produce the virus even in patients being actively treated.

“As a result of the persistence of cccDNA, antiviral therapies now have to administered lifelong for a majority of HBV patients in order to avoid a reactivation of the virus,” Kalkeri said.

“The bottom line is that long-term therapy is ineffective in eliminating HBV from infected patients and results in drug toxicity issues, as well as the emergence of viral resistance,” he added.

REASONS FOR OPTIMISM

While there are promising signs that hepatitis B research is making progress, the persistence problem may ultimately put a final cure out of reach, Kalkeri said. What could emerge, however, is a way to control the disease’s persistence, resulting a functional cure, he added.

“It’s more realistic to hope for a functional cure for HBV, which means viral replication would be suppressed and other functions would be restored to a normal level,” Kalkeri added.

One source of optimism revolves around the discovery that a cell surface protein known as NTCP acts a receptor for hepatitis B. In essence, NTCP opens the door for the virus to enter into healthy cells.

“With the discovery of NTCP, we could potentially use it as a tool in the laboratory to understand the mechanisms of HBV infection, cccDNA formation, and more,” Kalkeri said.

“At a minimum, this kind of infectious cell culture model would enable identification of HBV entry inhibitors and pave the way for combination studies along with other antiviral agents against this infection.”

Kalkeri said Southern Research’s HBV cure assay capabilities are available to advance research. These testing platforms are:

IN VITRO

Virus yield assay (HepG2.2.2.15 cells)

Infectious virus assay (HepG2-NTCP)

HBV core promoter assay

Inducible HBV cccDNA model (HepDE19)

IN VIVO

Adeno-Associated Virus-HBV mouse model (C57BL/6)

Using the tools developed for the HBV program and in collaboration with Southern Research’s Drug Discovery division, Kalkeri and his team have demonstrated the inhibition of HBV core promoter by a repurposed anti-cancer clinical candidate SRI-032007. The research shows that it is feasible to reduce the production of the viral genetic material in an in vitro laboratory setting. This work is being presented as a poster in September at the 2017 International HBV meeting in Washington, D.C. Additional testing in animal models of this compound is being planned. Finding new antivirals for HBV could complement the anti-HBV activity of current and help in the development of effective curative strategies.

Read an article on HBV by Kalkeri in Future Virology.

Southern Research specialist to collect solar eclipse data from stratosphere

Posted on July 25, 2017

When a total solar eclipse unfolds over the United States on Aug. 21, Southern Research communications engineer Donald Darrow will have a front row seat for the spectacular event some 50,000 feet above Earth.

Darrow will be aboard one of two NASA WB-57 high-altitude research planes flying in the stratosphere that day on a groundbreaking mission to capture the clearest views ever produced of the Sun’s outer atmosphere and the first thermal images revealing temperature shifts on the surface of Mercury.

“It certainly will be an exciting mission,” Darrow said. “I’m going to have the best view of probably anyone on the planet.”

Darrow is serving as the lead special equipment operator, or SEO, on the mission. His job is to operate a unique instrument developed by Southern Research called AIRS/DyNAMITE, which functions like an airborne telescope with special capabilities.

Southern Research solar eclipse — Southern Research’s Donald Darrow will operate the AIRS instrument on a NASA WB-57 aircraft during the total solar eclipse on Aug. 21.

The system is mounted on both of the WB-57 planes flying on the eclipse mission.

From nearly 10 miles above Earth, the AIRS/DyNAMITE’S high-speed, visible-light and infrared cameras will provide scientists with highly precise observations of the solar corona and the Sun’s nearest planetary neighbor.

The mission is being directed by Texas-based Southwest Research Institute, which brought in Southern Research to outfit the instruments with solar filters, new data recorders, and other upgrades. Darrow is flying on the WB-57 through Southern Research’s work with NASA’s Johnson Space Center in Houston.

Darrow has served as an SEO on WB-57 missions involving the AIRS/DyNAMITE equipment for around five years. The instrument, developed for the Space Shuttle program in 2004, has been deployed on a wide range of missions, from rocket launches to aircraft test flights.

“It’s a phenomenal asset, and everybody we show it to is very impressed by its capabilities, both by its versatility and by the resolution of its images,” Darrow said.

THE MISSION

On Aug. 21, Darrow’s day will be a long one.

It will start early that morning in Houston with three hours of equipment checks, briefings and other preparations. The flight to Carbondale, Illinois, the site picked to make observations because that’s where the total eclipse will last the longest, and back to Houston will take about six hours. After that, there will be debriefings and data transmission chores.

High above Carbondale, the two WB-57 aircraft will take turns collecting data on the eclipse for a combined total of around eight minutes. The fast-moving planes will be able to chase the moon’s shadow, giving Darrow and the other equipment operator additional time to make observations.

In addition, the AIRS/DyNAMITE instruments on the planes will capture thermal images of Mercury’s surface that could allow scientists to calculate temperatures on the planet’s entire night side for the first time.

Johanna Lewis, director of the Program Management Office in Southern Research’s Engineering Division, has worked with a SR team making modifications to the AIRS/DyNAMITE instruments to prepare them for the mission.

She said the long flight for Darrow will boil down to a few eventful minutes on Aug. 21.

“There may be millions of people on the ground watching exactly what he’s doing,” Lewis said. “He’s going to be involved in so much activity during a few minutes — tracking, making sure everything is in focus, making sure the system is operating just the way he wants, because he’s not going to get another chance to go around and do it again.”

While Darrow agreed that the mission promises to be a taxing one, the former Marine said he is confident it will go smoothly.

“This mission is very similar to our rocket launches in that we don’t get a second shot. If we miss this, we miss it,” he said. “When we are doing mapping, or something similar to that, we can always come back around for another pass.

“This time, it has go perfectly and smoothly. Otherwise, we don’t get the science.”

Darrow said he’s looking forward to seeing the scientific discoveries that come from the mission’s unprecedented look at the first total solar eclipse to track across the entire continental U.S. since 1918.

“We expect that within a few weeks of the data being delivered that we will have some preliminary observations about its quality and utility,” he said.

Southern Research readies for ‘Great American Eclipse’ viewing

Posted on July 20, 2017

Southern Research physicist Jim Tucker said a total solar eclipse cutting a path across the entire continental United States on Aug. 21 will offer dramatic views of a spectacular celestial event to millions – as long as they take precautions to observe it safely.

It’s the first total solar eclipse visible in the U.S. since 1979, though that one only touched a sliver of the Pacific Northwest. The last time a total solar eclipse crossed the entire U.S. was June 1918.

“It’s been a long, long time since a total eclipse was visible in the United States – and this one is particularly unique. They’re calling it the ‘Great American Eclipse’ because the U.S. is the only place where the total eclipse will visible,” said Tucker, who is director of Materials Research at Birmingham-based Southern Research.

Southern Research total solar eclipse — This NASA map shows the path of totality for the ‘Great American Eclipse.’

This path of totality, as it’s called, starts off in Salem, Oregon, and ends in Charleston, South Carolina, later that day. Along a 14-state path, day will turn to night for around two minutes as the moon’s shadow completely obscures the Sun.

And while people living outside a 70-mile-wide corridor on the total eclipse’s path won’t see the full show, everyone else in the lower 48 states will get a chance to see a partial eclipse.

In Birmingham, the eclipse will be 93 percent total, meaning there won’t be a total blackout but skies will get dim, he said.

“If it’s a sunny day, as you approach the mid-eclipse, you’re going to have this sensation of it getting cooler, like a really big cloud is coming over,” Tucker explained. “It will seem cooler and darker. The Sun – you shouldn’t look at it without protection – will appear to have a bite out of it.”

SAFE VIEWING

Tucker stressed that everyone should use proper viewing equipment to observe the eclipse, or construct a pinhole camera to observe a projected image of the Sun.

“You should never look at the Sun. There’s never a time you should look at the eclipse without proper solar viewing equipment,” he said. “That does not include looking through three layers of sunglasses. That will not be OK because there will be ultraviolet rays getting through. Even though you cannot see UV rays, they can damage your retina.”

Southern Research is offering a spot to safely take in the Great American Eclipse.

From 12:30-2 p.m. Aug. 21, Southern Research will host a free eclipse-viewing event at its downtown Birmingham campus, where solar viewing glasses will be distributed. In addition, a telescope fitted with a solar filter will offer a detailed look at the Sun during the eclipse.

Visitors can also view live broadcast feeds of the eclipse from NASA and two of the agency’s WB-57 high-altitude research planes outfitted with a special high-definition imaging system developed by Southern Research.

HOW AN ECLIPSE HAPPENS

Tucker, an avid amateur astronomer, said a total solar eclipse happens when the alignment of the moon and Sun are just right. While the moon circles the Earth every month and nominally travels between the Earth and Sun, it has to be exactly in line with the Sun to cast a shadow on the Earth’s surface.

The Sun is much larger than the moon but also much more distant from Earth. As it happens, the Sun and moon appear about the same size in the sky, with the moon appearing larger when it’s closest to Earth and slightly smaller when at the farthest point in its orbit.

That can make a difference in a solar eclipse. There are times when the alignment is right but the moon doesn’t fully cover the Sun even at mid-eclipse, creating what looks like a ring of fire around the darkened solar disc. This is called an annular eclipse.

In a total eclipse, the moon appears bigger than the Sun and totally blocks its light for a period of time. At its longest duration, the “Great American Eclipse” will last for just over two and half minutes. In eclipses occurring when the moon is at its closest point to Earth, totality can last for more than seven minutes.

SECOND TOTAL ECLIPSE

On Aug. 21, Tucker plans to be near Kansas City, Missouri, to view his second total solar eclipse, where he hopes to encounter clear skies. The first was in 1970, when his family traveled to the Florida Panhandle.

“I was 8 years old, and I still remember it like it was yesterday. It was an incredible experience, even though it was cloudy. Still, it was amazing that in the middle of the day it got totally dark,” he said.

The next total solar eclipse to cross the U.S. will be in April 2024 on a path that takes it from Texas north to the Great Lakes.

Tucker’s career includes contributions to the James Webb Space Telescope, a next-generation successor to the Hubble telescope that NASA plans to launch in 2018.

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