Joe Gray and his research team at Berkeley Lab have found a new candidate gene—Annexin A9 (ANXA9)––to enhance multigene assays for detecting invasive breast cancer. In a five-year study of patients with breast cancers, the Berkeley Lab researchers examined tissue samples and found that ANXA9 expressed abnormally high levels of protein in approximately half of the patients. This indicates a significant relationship between ANXA9 and aggressive breast cancers. Therefore, ANXA9 can be used as a prognostic marker in the early identification of aggressive forms of breast cancer. In addition, the researchers demonstrated that ANXA9 suppresses apoptosis (programmed cell death), a process in which abnormal cells such as cancer cells self-destruct. When ANXA9 is silenced, apoptosis is induced, which decreases breast cancer cell proliferation and may, therefore, prevent breast cancer tumors from growing and spreading to other tissues. Given this potential, the Berkeley Lab invention promises to increase the chances of survival among patients who are resistant to standard chemotherapy. Currently, breast cancer patients may be effectively diagnosed and treated at the genomic level through multigene assays, a method for identifying patients whose tumors test positive for genes associated with aggressive breast cancers. Prior to the Berkeley Lab invention, however, the accuracy of multigene assays had been limited by the small number of genes assayed.

A research team led by John Hartwig and Douglas Clark of Berkeley Lab has synthesized artificial metalloproteins containing non-biologic porphyrins. These modified metalloproteins can catalyze a wider range of biologic and abiologic reactions, with a variable precious metal placed at the center dictating the selectivity and efficiency of these processes. Because this process does not alter the protein conformation or the enzyme active site, these molecules are capable of catalyzing processes efficiently and with extreme specificity. Preparation of these molecules is both cost effective and well understood, making these artificial metalloproteins ideal for use in both research and production based sectors. Proteins that contain a metal-porphyrin cofactor are deconstructed and the naturally occurring metal within the active site is replaced with an abiologic noble metal. The native structure of the protein is not altered, and reactants enter the fully functional active site. The artificial metalloenzyme within the protein would be able to perform a wider range functions, including transport, sensing, and catalysis. One such novel reaction this modified metalloprotein is able to catalyze is the insertion of a carbene into a carbon-hydrogen bond.

For the researchers’ complete publication ACS NanoLetters, go here. Direct solar-powered production of value-added chemicals from CO2 and H2O, a process that mimics natural photosynthesis, is of fundamental and practical interest. In natural photosynthesis, CO2 is first reduced to common biochemical building blocks using solar energy, which are subsequently used for the synthesis of the complex mixture of molecular products that form biomass. Here we report an artificial photosynthetic scheme that functions via a similar two-step process by developing a biocompatible light-capturing nanowire array that enables a direct interface with microbial systems. As a proof of principle, we demonstrate that a hybrid semiconductor nanowire–bacteria system can reduce CO2 at neutral pH to a wide array of chemical targets, such as fuels, polymers, and complex pharmaceutical precursors, using only solar energy input. The high-surface-area silicon nanowire array harvests light energy to provide reducing equivalents to the anaerobic bacterium, Sporomusa ovata, for the photoelectrochemical production of acetic acid under aerobic conditions (21% O2) with low overpotential (η < 200 mV), high Faradaic efficiency (up to 90%), and long-term stability (up to 200 h). The resulting acetate (∼6 g/L) can be activated to acetyl coenzyme A (acetyl-CoA) by genetically engineered Escherichia coli and used as a building block for a variety of value-added chemicals, such as n-butanol, polyhydroxybutyrate (PHB) polymer, and three different isoprenoid natural products. As such, interfacing biocompatible solid-state nanodevices with living systems provides a starting point for developing a programmable system of chemical synthesis entirely powered by sunlight.

Dominique Loqué, Henrik V. Scheller, and colleagues at the Joint BioEnergy Institute (JBEI) have developed a technology that can be used to fine-tune desirable biomass traits in plants. A key feature of the invention is the design of an artificial positive feedback loop whereby a transcription factor induces increased transcription of itself. Gene promoters are selected according to the desired outcome, for example, to improve saccharification efficiency or to raise the level of desirable hexose sugars in relation to hard-to-ferment pentoses. Some promoters can boost secondary cell wall deposition of cellulose; others can decrease deposition of lignin or hemicellulose (xylan). With similar promoter engineering, increased wax production can be directed to the epidermal layers of a plant, improving drought tolerance and efficient water use while preserving energy for increased production of biomass. This versatile technology can be used to improve crops used for biofuels and paper production; provide livestock with more digestible forage; extend the range of crops to marginal land; or produce stronger timber for construction, among other applications. Unlike other genetic engineering methods, when applied to increasing secondary cell wall deposition, the JBEI technologies alter biosynthesis in plant fibers but not in vascular tissue or leaves. Thus they do not adversely affect growth, fertility, or the fruit- or grain-bearing capacity of the plants. Because this new method involves dominant traits and uses genetic promoters that are part of conserved pathways, it will be applicable across many species, including polyploids and sterile plants. Moreover, its application does not require sequencing of the entire genome of the target plant or the presence of a particular variety or cultivar. To date, the technology has been applied to four applications, described below:

Sylvain Costes and Rafael Gómez-Sjöberg of Berkeley Lab have invented a technology that will improve screening techniques used by hospitals, pediatric clinics, the nuclear industry, research laboratories, and the military to identify people who may be sensitive to low doses of ionizing radiation emitted by imaging devices such as X-rays and computed tomography (CT) scans, or by nuclear reactors. Unlike genetic assays, which test for the expression of a gene associated with a certain disease, the Berkeley Lab invention uses a functional assay that measures the DNA repair kinetic, or repair rate, in the living cells of a patient’s blood sample. Individuals with a slow DNA repair rate have a higher probability of developing long-term mutations and cancer when their DNA is damaged by ionizing radiation or other environmental factors. By identifying individuals with a slow DNA repair rate, the invention will protect patients and radiation workers from ionizing radiation doses that may put their health at risk. The invention includes a microfluidic device designed for automated, high-throughput screening and is robust enough to analyze as many as 30 samples or people in one day. Due to the Berkeley Lab device’s compact design, it requires only small, microfluidic samples. The approach is scalable, and could be developed for much higher throughput. To achieve superior speed and accuracy, the Berkeley Lab researchers developed a method to quickly quantify the DNA repair kinetic in blood samples irradiated ex vivo. The invention accurately measures an individual’s repair kinetic response to a range of doses, from low CT-scan levels to high radiotherapy levels, within 24 hours. The new assay would be inexpensive, offering patients an affordable way to monitor their DNA repair kinetic, and to track whether a change in diet and lifestyle improves it. The invention can be used by a laboratory or physician’s office to document a patient’s DNA repair kinetic. Children are more at risk than adults for developing radiation-induced cancer. While it is well accepted by researchers that cells with DNA mutations can take as long as 20 years to progress into a full cancer, with the Berkeley Lab assay, children who are more prone to DNA damage will be able to get a head start on protecting their future health. For example, the Berkeley Lab assay may be used by pediatric hospitals or clinics to recommend MRI or ultrasound as non-radiation diagnostic alternatives to X-rays or CT scans.

Jonathan Maltz of Berkeley Laboratory has developed a method of measuring endothelial function using a standard blood pressure cuff. The Berkeley Lab technology measures a different parameter than flow-mediated vasodilation (FMD) measurement. As a result, the new invention provides measurements more sensitive to change over time for an individual patient compared to FMD. The Berkeley Lab technology can be used in almost any setting, and it can be applied to arteries in the arms and legs. The current state-of-the-art, FMD, measures the change in diameter in the brachial artery before and after shutting off blood flow. FMD requires the use of an ultrasound scanner or expensive systems such as Endo-PAT and Vendys, making the current technology unsuitable for frequent testing or continuous monitoring. In addition, the measurements by some FMD systems are based on microvasular tone, which can be compromised by factors such as sympathetic nervous activation. The Berkeley Lab invention overcomes these challenges to enable more convenient patient testing. Frequent, sensitive measurement of endothelial function may identify the earliest signs of cardiovascular disease in a particular patient. Regular testing may also be used to monitor the effects of interventions such as exercise, smoking cessation, dietary modification and cholesterol-lowering therapy. Patient compliance can be improved by providing weekly or daily feedback. Finally, the measurements provided by the device can be employed as sensitive endpoints for clinical trials of new interventions.

In spite of the public’s growing interest in the effects of DNA damage on human health, and the ability to repair some DNA damage through lifestyle and nutrition choices, there is no at-home blood test for assessing DNA damage and monitoring it over time. Researchers at Berkeley Lab and Exogen Biotechnology have developed a kit that permits in-home, sterile collection of a small blood sample to be used for DNA damage assessments. Fixation solutions within the kit’s collection tubes preserve blood cell structures and DNA damage markers making cells compatible with lab testing such as cell isolation and immunofluorescent staining. The fixation solution also ensure collected samples are non-toxic to meet shipping regulations. Once the mailed sample reaches a lab, it undergoes a process to extract and capture nucleated lymphocytes so they can be immunostained for reproducible quantification of DNA damage levels. This isolation of specific white blood cells can be achieved using just a few drops of blood (10 – 100 μl). Cells are then imaged on a high-throughput imaging plate. An automated computer scoring and analysis process compares detected DNA damage levels to a baseline or other reference level based on the age, health status, location, history of toxin exposure, and other factors affecting DNA. The results can be shared with patients, and further samples collected and tested over time can demonstrate DNA damage level optimization due to corrective changes in lifestyle or nutrition. A current method for carrying out DNA damage analysis uses high-speed automated image analysis and robotics to examine blood tissue samples quickly for quantitative indicators of radiation exposure. However, analysis of patient samples must be carried out on site. Current available tools have not been tested and refined for physiological levels of DNA damage, do not address sorting specific white cells, and do not take the patient’s age into account for data interpretation – all factors found by the Berkeley Lab / Exogen researchers as required for accurate interpretation of DNA damage levels.

Optical modulators with ultrahigh speed, small footprint, large bandwidth, robust athermal operation, and complementary metal-oxide semiconductor (CMOS) compatibility are important devices for optical communication and computing applications. Compared to the conventional optical modulators, graphene modulators have attracted great interest due to their large optical bandwidth with an ultracompact footprint. However, their practical applications are limited by the trade-off between speed and optical bandwidth, with a critical issue of temperature tolerance. In this work, we experimentally demonstrate an athermal graphene optical modulator with a 140 nm bandwidth in the entire optical communication regime (1500–1640 nm), with robust high-temperature operation. The device is based on a planar structure with double-layer graphene, leading to the high modulation speed, up to 35 GHz through reduction of the total resistance, and capacitance (9 fF). We observe speed stability in a wide range of temperatures (25–145 °C). The ultracompact footprint (18 μm2) of the device promises the next generation of on-chip optical interconnections for efficient communication.