The bacterium Clostridium difficile (often called C. diff) can cause severe intestinal infections, responsible for about 500,000 cases and 29,000 deaths in the United States per year. While infections are more often found in ill and elderly people, infection rates are increasing in young and healthy people. The bacterium makes and secretes two related toxins, TcdA and TcdB. Understanding the structure of these molecules is a critical step to developing treatment. Unfortunately, since these toxin proteins are huge and flexible, scientists have been unable to determine the entire molecular structures until now.
Approximately 1,700 scientists visit SSRL annually to conduct experiments in broad disciplines including life sciences, materials, environmental science, and accelerator physics. Science highlights featured here and in our monthly newsletter, Headlines, increase the visibility of user science as well as the important contribution of SSRL in facilitating basic and applied scientific research. Many of these scientific highlights have been included in reports to funding agencies and have been picked up by other media. Users are strongly encouraged to contact us when exciting results are about to be published. We can work with users and the SLAC Office of Communication to develop the story and to communicate user research findings to a much broader audience. Visit SSRL Publications for a list of the hundreds of SSRL-related scientific papers published annually. Contact us to add your most recent publications to this collection.
August 2019
Macromolecular Crystallography, Biological Small-angle X-ray Scattering (BioSAXS)
BL4-2, BL9-2
July 2019
The field of superconductivity was surprised by the discovery of a manganese-based superconductor, published in 2015. Because the electrons in manganese do not form couplets called Cooper pairs, it was not thought possible that manganese could have traits of superconductivity. This discovery necessitates a revised explanation for superconductivity, one not requiring Cooper pairing. The unconventional pairing of electrons in the manganese superconductor MnP provides a novel system to understand the phenomenon of superconductivity.
Resonant soft x-ray scattering (RSXS)
BL13-3
June 2019
The development of better rechargeable batteries for consumer electronics and electric vehicles is difficult due to the complex interplay of many chemical, spatial, and temporal factors. Taken together, these factors are called the chemomechanical interplay, which includes chemical degradation, chemical heterogeneity, and mechanical stress that cause the battery to lose functionality over many charging and discharging cycles. A team of researchers has developed a combined methods approach that allows quantification of the processes of chemomechanical interplay over diverse length and time scales.
TXM, X-ray Absorption Spectroscopy
BL6-2c, BL13-3
May 2019
Every year the flu vaccine contains a different formulation, due to multiple influenza virus strains and their ability to mutate. Scientists are working toward the universal flu vaccine, which would target conserved regions of the virus. Such a vaccine would be effective regardless of virus strain or genetic drift due to mutation, requiring no yearly updates. Current research focuses on the virus’s hemagglutinin (HA) stem region, which is targeted by our immune system’s broadly neutralizing antibodies (bnAbs). A team of researchers from Scripps and Janssen developed bnAbs to HA, which proved successful in preventing influenza infection in mice. Some of these are now being evaluated for effectiveness in human clinical trials. The team is now focused on finding an effective small molecule based on their bnAbs, which would have the advantage of oral delivery.
Macromolecular Crystallography
BL12-2
May 2019
Radioisotope therapies improve on traditional chemotherapies by being finely targeted to only the diseased cells and leaving surrounding healthy cells unharmed. A promising radioisotope for therapeutic uses is 119Sb, which releases low energy Auger electrons that can kill cancer cells. A problem with widespread use of drugs using 119Sb is its short half-life of around 38 hours. A team of scientists from Los Alamos National Laboratory have developed a novel strategy for utilizing 119Sb.
X-ray Absorption Spectroscopy
BL11-2
March 2019
Our genetic information is stored in DNA using just four nucleotide bases: A, C, G, and T. While we may never understand how these particular molecular combinations came to store the instructions for all life on Earth, we can address some questions about their role, such as: are these the only four bases that could create a DNA double helix with the right balance of stability and flexibility for cells to store and access genetic information? A team of scientists answered this question by introducing four new, synthetic bases into DNA, forming “hachimoji DNA,” named using the Japanese words for eight letters.
Macromolecular Crystallography
BL14-1
March 2019
The massive consumption of fossil energy and the associated environmental deterioration have led to global concern that calls for innovations in energy technologies. Energy storage is a vital component in this field because it could facilitate ground breaking changes in modern lifestyle by affecting how the energy is stored, transported and consumed. The deployment of lithium ion battery in electric vehicles (EVs) is a good example of this kind, which, however, puts stringent requirements on their rechargeable batteries, including high energy density, high power density, long cycle/calendar life and low cost.
February 2019
Acute lymphoblastic leukemia (ALL) is an aggressive malignancy of the bone marrow that currently stands as the most common form of cancer in children. DNA sequencing studies comparing diagnostic and relapse patient samples have identified relapse-driving mutations in the cytosolic 5’-nucleotidase II (NT5C2) gene. The role of the NT5C2 enzyme is to degrade purines so they can be exported from the cell. NT5C2 can also degrade and inactivate thiopurine chemotherapy molecules, causing resistance to ALL treatments.
Macromolecular Crystallography
BL12-2, BL14-1
February 2019
General anesthetics like alphaxalone (5α-pregnan-3α-ol-11,20 dione) bind to type A γ-aminobutyric acid receptors (GABAARs), which are gated ion channels that reduce the potential of neurons to fire. Experimental evidence points to GABAAR’s transmembrane domain (TMD) as the allosteric site of drug binding. The TMD is known to be responsible for allowing the ion channel to transition between the resting, activated, and desensitized states. A team of scientists has studied where alphaxalone binds to GABAAR and how this affects its function.
Macromolecular Crystallography
BL12-2
January 2019
While a small amount of copper is essential for living organisms, too much copper contaminating our soils can be toxic and pose a serious problem. Copper has an affinity for organic matter in soils, where it mainly exists in the two redox states Cu(I) and Cu(II). In soils that fluctuate in redox conditions, the mobility of copper through the environment can be hard to predict. Mofette sites, produced by CO2 degassing usually found in seismically active areas, are good natural laboratories due to their wide range of soil redox conditions and of soil organic matter composition within a small area. Near the sites of CO2 degassing, the soil is anoxic and organic matter does not decompose well. The soils transition to oxic conditions just a few meters away. A team of researchers studied the behavior of copper in the natural gradient of a mofette site in the Czech Republic.
X-ray Absorption Spectroscopy
BL4-1, BL4-3
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