DURHAM, N.C. -- During World War II, the Soviet Red Army was forced to move their biological warfare operations out of the path of advancing Nazi troops. Among the dangerous cargo were vials of Francisella tularensis, the organism that causes tularemia and one of the worlds most infectious pathogens.

Years later, a Soviet defector claimed that his country had unleashed their stores of F. tularensis on German soldiers, weakening them shortly before the pivotal Battle of Stalingrad. Others believe the outbreak on the German-Soviet front was more likely spread by rats, not Russians. Yet no one has disputed the bacterias capacity to inflict harm.

The Centers of Disease Control ranks tularemia as one of the six most concerning bioterrorism agents, alongside anthrax, botulism, plague, smallpox and viral hemorrhagic fever. And Russian stockpiles of it likely remain.

American scientists studying F. tularensis recently mapped out the complex molecular circuitry that enables the bacterium to become virulent. The map reveals a unique characteristic of the bacteria that could become the target of future drug development.

The research appeared early online Sept.1 and will be in the Sept. 13, 2017 journal Genes & Development.

Now we have the coordinates for stopping one of the most infectious agents known to man. By having all of these pieces, and understanding how they fit together, we can design new drugs that can shut down virulence, said Maria A. Schumacher, Ph.D., senior study author and the Nanaline H. Duke Professor of Biochemistry at the Duke University School of Medicine.

F. tularensis is an exceptionally hardy organism that can infect a variety of hosts, including humans, rabbits and mosquitos, and can survive for weeks at a time in dead and decaying carcasses. It is so virulent that a person only has to inhale 10 microscopic particles of the bacterium to become infected. The Russians and Japanese, as well as the Americans and their allies, all explored its potential as a biological weapon during World War II.

After the war, Russians continued to develop the agent, searching for mutations that could make it resistant to antibiotics and thus even more deadly. The World Health Organization has since projected that 110 pounds of F. tularensis dispersed over a city of 5 million people would cause about 250,000 cases of severe illness, and 19,000 deaths.

Despite decades of fervent study, the factors that make this bacterium so pathogenic are still not fully understood. Recently, a cluster of genes called the Francisella pathogenicity island emerged that is essential for its virulence. In this study, researchers carried out a battery of structural, biochemical and cellular studies to define the molecular factors that turn these pathogenicity genes on and off.

They suspected that a stress-sensing molecule or alarmone called ppGpp might play a role. Alarmones are known to respond to stressful conditions by promoting survival and virulence in bacteria.

Lead study author and Duke graduate student Bonnie J. Cuthbert started by looking at factors that might interact with ppGpp, such as the aptly named protein pathogenicity island gene regulator or PigR, the macrophage growth locus protein A or MglA, and the stringent starvation protein A or SspA. Cuthbert used a technique called x-ray crystallography to produce atomic-level three-dimensional structures of each of these proteins, and then assembled them one by one, like the components of a circuit board.

She found that MglA and SspA partner up to form a two-part protein that contains a unique binding pocket on its underside for ppGpp. Once this molecule is bound, it recruits PigR and subsequently stabilizes RNA polymerase to this area of the F. tularensis genome, creating a large complex that latches onto the DNA to flip on the pathogenicity genes.

The researchers then created mutations that destroyed the binding pocket for ppGpp. They found that when the alarmone couldnt bind, pathogenicity couldnt be activated.

We have uncovered a totally novel way for controlling virulence, said senior study author Richard G. Brennan, Ph.D., James B. Duke Professor of Biochemistry and Chair of Biochemistry at Duke University School of Medicine and also an advisor to Cuthbert. If we could block this binding pocket, then we could stop virulence in F. tularensis. It would be a new way of fighting this bacteria, by disabling it with antivirulence drugs rather than by killing it outright with antibiotics.

The research was supported by aNational Institutes of Health grants GM115547,GM37048, and AI081693. The Berkeley Center for Structural Biology is supported in part by the National Institutesof Health, the National Institute of General Medical Sciences, and the Howard Hughes Medical Institute. The ALS issupported by the Director, Office of Science, Office of Basic EnergySciences of the US Department of Energy under contract numberDEAC02-05CH11231.

CITATION: Dissection of the molecular circuitry controlling virulence in Francisella tularensis, Bonnie Cuthbert, Wilma Ross, Amy Rohlfing, Simon Dove, Richard Gourse, Richard G. Brennan, and Maria A. Schumacher. Genes & Development, September 13, 2017. DOI: 10.1101/gad.303701.117

http://genesdev.cshlp.org/content/early/2017/09/01/gad.303701.117.full.pdf+html?sid=f7d8a806-f7ee-4da3-ac9e-1f1f4f82f5c3

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Molecular Map Shows How to Disable Dangerous Bioweapon ... - Duke Today

In BriefScientists at the University of Melbourne have established a new method of imaging biochemistry at the nanoscale. It's hoped that this could lead to a better understanding of neuro-degenerative diseases.

A group of scientists at the University of Melbourne have developed a new means of inspecting biochemistry at the nanoscale. The teams study centers around a quantum kangaroo that is revealed by the tools capacity to detect electron spins at resolutions that were never before possible.

Electron spin resonance (ESR) methodology has been used to help scientists understand biochemical processes in biomechanical systems for quite some time. However, in the past, billions of electronic spins have been required to produce a legible image.

This new project uses an array of quantum probes in diamond to perform non-invasive ESR imaging at a sub-cellular resolution. Its capable of producing images from only a few thousand electron spins.

The sensing and imaging technology we are developing enables us to view life in completely new ways, with greater sensitivity and resolution derived from the fundamental interactions of sample and probe at the quantum mechanical level, Professor Lloyd Hollenberg, who lead the project, told Phys.

Its hoped that this new non-invasive technique could help researchers get a better idea of how transition metal ions like copper play into diseases affecting the brain.

Transition metal ions are implicated in several neuro-degenerative diseases, however, little is known about their concentration and oxidation state within living cells, Dr. David Simpson, lead author the paper and co-head of sensing and imaging at the Centre for Neural Engineering. explained to Phys.Click to View Full Infographic

The University of Melbournes Centre for Quantum Computation and Communication Technology is making great strides when it comes to using quantum technology to improve imaging techniques. In April 2017, a team at the institution was able to capture the movements of electrons in 2D graphene.

Nanotechnology is set to have a huge impact on medicine, and not just in terms of imaging. Recent advances have facilitated projects like a breathalyzer that can detect the flu, and a nanoparticle that can remove toxins administered by snake bites but of course being able to check out whats happening at the nanoscale is incredibly valuable in terms of both diagnosis and research.

See the article here:
Australian Scientists Have Developed a New Tool for Imaging Life at the Nanoscale - Futurism

After Kite Pharma exit last week, and number of successes in the field of medical, biological and pharmaceutical research, we can learn how significant Israel is to the world research in biochemistry by hosting the International Congress in this field. FEBS (Federation of European Biochemical Societies) will hold their prestigious International Congress next week at ICC Jerusalem

About 40,000 scientists from 37 countries (from Britain in the west to Armenia in the east) are members of FEBS. This will be the 42nd conference of the organization, and this year the main topic of the conference is 'From molecules to cells and back.'

More than 1,200 prominent researchers, scientists and doctors from Europe and more than 500 researchers and academics from Israel are expected to attend the prestigious conference, which will take place on September 10-14.

Prof. Michal Sharon, vice chairman of the Israel Society for Biochemistry and Molecular Biology, says:"It was a great achievement to convince the organization's leadership to come to Israel, the decision was made at a problematic time, during the military Operation " Protective Edge", when various groups in the world called for a boycott of the State of Israel. Nevertheless, Prof. Abdussalam Azem (Professor of Life Sciences at Tel Aviv University) and Professor Israel Pecht, who served as general secretary of FEBS at the time, succeeded in convincing to hold the Congress in Israel, thanks to its esteemed status in the world, as a leading country for research in the field of biochemistry and molecular biology. "

According to Prof. Michal Sharon: "The organization's management held a vote, and in the end elected to come to ICC Jerusalem in 2017. As time approaches, the excitement in Israel among researchers and practitioners in these areas is evident. We are preparing for a fascinating conference, and we hope that during the course of it some new scientific discoveries will be revealed for relief of all humanity. "The conference will include professional scientific discussions in such fields as: cancer biology, metabolomics and signaling pathways, chromatin structure and post-genetic editing processes, career and education, women in science, and more.

Among the conference guests expected to arrive to Israel are Nobel Prize Laureate in Chemistry (2012), Prof. Robert Joseph Lefkowitz from Duke University (USA), who has won a prize for his research of G-protein-coupled receptors, Prof. Carol Robinson from University of Oxford, who studies Membrane protein complexes, Prof. Feng Zhang from the Massachusetts Institute of Technology (MIT), who contributed a lot to development of the CRISPR method for genetic modification and more others.

This week, one week before the congress, FEBS is organizing the Young Scientists Forum (YSF), which brings together about 150 young researchers and promotes scientific and social connections between them. Students from all over Europe and Israel arrive at this gathering this week at Kibbutz Ramat Rachel on the suburbs of Jerusalem.

"We are preparing to host this important international conference and are aware of its contribution to the city of Jerusalem, to Israeli science and to the Tourism industry," said Mira Altman, CEO of the International Convention Center.

Altman adds: "The conference tourism has the potential to bring into the Israeli economy over 60 million $ a year."

The Federation of European Biochemical Societies and the Israel Society for Biochemistry and Molecular Biology, work to promote and improve research, science and cooperation in the field.

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Federation of European Biochemical Societies head to Jerusalem - ITCM

Australian scientists have developed a new tool for imaging life at the nanoscale that will provide new insights into the role of transition metal ions such as copper in neuro-degenerative diseases.

In a new paper published in Nature Communications, a team of researchers at the University of Melbourne reveal a "quantum kangaroo" that demonstrates a way to detect and image electronic spins non-invasively with ambient sensitivities and resolution orders of magnitude never before achieved. The breakthrough will provide physicians and researchers with a new tool for probing the role transition metal ions play in biology and disease.

Electron spin resonance (ESR) techniques have been a mainstay in understanding biochemical processes in biological systems. Yet ESR has not seen the rapid growth compared to its sister technology, nuclear magnetic resonance, which is now a mature technology used in magnetic resonance imaging (MRI) to look inside the body.

Both ESR and NMR apply a magnetic field to image molecules, but unlike NMR, ESR can reveal biochemistry related to metal ions and free radicals. The challenge is that in biological systems the detectable concentration of electron spins is many orders of magnitude lower than nuclear spins. Hence, the roadblock for the development of ESR-based imaging techniques has been the sensitivity required - typically billions of electronic spins have been needed to generate a sufficient signal for successful imaging.

Enter: quantum technology. A team led by Professor Lloyd Hollenberg has used a specially engineered array of quantum probes in diamond to demonstrate non-invasive ESR imaging with sub-cellular resolution. Remarkably, the system is able to image and interrogate very small regions containing only a few thousand electron spins.

"The sensing and imaging technology we are developing enables us to view life in completely new ways, with greater sensitivity and resolution derived from the fundamental interactions of sample and probe at the quantum mechanical level," said Hollenberg, who is Deputy Director of the Centre for Quantum Computation and Communication Technology (CQC2T) and Thomas Baker Chair at the University of Melbourne.

"This dramatic improvement in ESR imaging technology is an exciting development and a clear demonstration of how quantum technology can be used to enhance signal sensitivity and provide solutions to long standing problems, for example probing human biochemistry at even finer scales."

Scaling ESR technology down to sub-micron resolution has been challenging because such a reduction in spatial resolution requires substantially better sensitivity. However, this is precisely what quantum probes offer - high sensitivity with high spatial resolution.

By generating an array of quantum probes in diamond, using the material's unique nitrogen-vacancy colour centre, the interdisciplinary research team was able to image and detect electronic spin species at the diffraction limit of light, 300 nanometres. Critically, the sensing technology is able to provide spectroscopic information on the particular source of electronic spins being imaged.

Dr David Simpson, lead author and co-head of sensing and imaging at the Centre for Neural Engineering said that the technology can provide new insight into the role transition metal ions play in biology.

"Transition metal ions are implicated in several neuro-degenerative diseases, however, little is known about their concentration and oxidation state within living cells," he said.

"We aim to adapt this new form of sensing to begin probing such effects in a range of biological systems."

One of the unique advantages of quantum-based sensing is that it does not interfere with the sample being imaged. Other approaches rely on fluorescent molecules binding to particular targets of interest. While these approaches are species-specific, they modify the functionality and availability of the target species being imaged.

PhD student and co-author on the paper Robert Ryan explained the technique.

"Our technique relies on passive, non-invasive detection of electronic spins by observing their interaction with the quantum probe array," said Ryan.

"By carefully tuning an external magnet into resonance with the quantum probes, we are able to listen to the magnetic noise created by the sample's electronic spins. Different electronic spin species have different resonance conditions; therefore we are able to detect and image various electronic spin targets."

A key to the success of the work was collaboration among the team members, who were drawn from different research centres across the university.

"The interdisciplinary aspect of this research helped push the boundaries of what is possible," said Professor Paul Mulvaney, co-author and Director of the Centre for Exciton Science in the School of Chemistry at the University of Melbourne.

"From a chemistry perspective, it is surprising to see that a fragile quantum system can accommodate the fluctuating environment encountered in ?real' chemical systems and the inherent fluctuations in the environment of ions undergoing ligand rearrangement. The complementary expertise within chemistry, physics and neuroscience has led to this advance."

Research paper

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Aussie quantum tech has its sights set on human biochemistry - Space Daily