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Golden, CO, United States

Biosciences Center

Golden, CO, United States
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Lima J.G.,Hospital Universitario Onofre Lopes | Lima J.G.,Federal University of Rio Grande do Norte | Nobrega L.H.C.,Hospital Universitario Onofre Lopes | Lima N.N.,Hospital Universitario Onofre Lopes | And 14 more authors.
Bone | Year: 2017

Context Berardinelli–Seip Congenital Lipodystrophy (BSCL) is a rare autosomal recessive syndrome characterized by a difficulty in storing lipids in adipocytes, low body fat mass, hypoleptinemia, and hyperinsulinemia. Sclerostin is a product of SOST gene that blocks the Wnt/β-catenin pathway, decreasing bone formation and enhancing adipogenesis. There are no data about sclerostin in people with BSCL. Objective We aimed to evaluate serum sclerostin, bone mineral density (BMD), and L1–L4 Trabecular Bone Score (TBS) in BSCL patients, generating new knowledge about potential mechanisms involved in the bone alterations of these patients. Design, setting, and patients In this cross-sectional study, we included 11 diabetic patients with BSCL (age 24.7 ± 8.1 years; 6 females). Sclerostin, leptin, L1–L4 TBS, BMD were measured. Potential pathophysiological mechanisms have been suggested. Results Mean serum sclerostin was elevated (44.7 ± 13.4 pmol/L) and was higher in men than women (55.3 ± 9.0 vs. 35.1 ± 8.4 pmol/L, p = 0.004). Median of serum leptin was low [0.9 ng/mL (0.5–1.9)]. Seven out of 11 patients had normal BMD, while four patients had high bone mass (defined as Z-score > + 2.5SD). Patients on insulin had lower sclerostin (37.3 ± 9.2 vs. 52.6 ± 13.4 pmol/L, p = 0.05). The mean TBS was 1.402 ± 0.106, and it was higher than 1.300 in nine patients. Conclusions Patients with lipoatrophic diabetes (BSCL) have high serum concentrations of sclerostin, normal or high BMD, and reasonable trabecular bone mass measured by TBS. This is the first report of high sclerostin and good bone microarchitecture (TBS) in BSCL patients. © 2017 Elsevier Inc.


Singh R.,University of Illinois at Urbana - Champaign | Sivaguru M.,University of Illinois at Urbana - Champaign | Fried G.A.,University of Illinois at Urbana - Champaign | Fouke B.W.,University of Illinois at Urbana - Champaign | And 3 more authors.
Journal of Contaminant Hydrology | Year: 2017

Physical, chemical, and biological interactions between groundwater and sedimentary rock directly control the fundamental subsurface properties such as porosity, permeability, and flow. This is true for a variety of subsurface scenarios, ranging from shallow groundwater aquifers to deeply buried hydrocarbon reservoirs. Microfluidic flow cells are now commonly being used to study these processes at the pore scale in simplified pore structures meant to mimic subsurface reservoirs. However, these micromodels are typically fabricated from glass, silicon, or polydimethylsiloxane (PDMS), and are therefore incapable of replicating the geochemical reactivity and complex three-dimensional pore networks present in subsurface lithologies. To address these limitations, we developed a new microfluidic experimental test bed, herein called the Real Rock-Microfluidic Flow Cell (RR-MFC). A porous 500 μm-thick real rock sample of the Clair Group sandstone from a subsurface hydrocarbon reservoir of the North Sea was prepared and mounted inside a PDMS microfluidic channel, creating a dynamic flow-through experimental platform for real-time tracking of subsurface reactive transport. Transmitted and reflected microscopy, cathodoluminescence microscopy, Raman spectroscopy, and confocal laser microscopy techniques were used to (1) determine the mineralogy, geochemistry, and pore networks within the sandstone inserted in the RR-MFC, (2) analyze non-reactive tracer breakthrough in two- and (depth-limited) three-dimensions, and (3) characterize multiphase flow. The RR-MFC is the first microfluidic experimental platform that allows direct visualization of flow and transport in the pore space of a real subsurface reservoir rock sample, and holds potential to advance our understandings of reactive transport and other subsurface processes relevant to pollutant transport and cleanup in groundwater, as well as energy recovery. © 2017 Elsevier B.V.


Neto C.,University of Lisbon | Fonseca J.P.,Biosciences Center | Costa J.C.,University of Lisbon | Bioret F.,University of Western Brittany
Acta Botanica Gallica | Year: 2015

Omphalodes kuzinskyanae Willk. is an endangered annual plant of the family Boraginaceae, endemic to a narrow coastal area in the Lisbon region (Portugal). Omphalodes littoralis Lehm. occurs in northwest Spain (subsp. gallaecica) and northwest France (subsp. littoralis). Three approaches were used to assess the ecological requirements of O. kuzinskyanae: (1) physical and chemical characterization of their habitat soil; (2) phytosociological analysis; (3) comparison of several life history parameters under different light conditions. Germination experiments were conducted to evaluate seed dormancy. The results show that O. kuzinskyanae occurs in thin sandy soil with a substantial amount of organic matter and clay, mostly over limestone pavements. Phytosociological analysis shows that O. kuzinskyanae occurs both in sciophytic and heliophytic communities. Life history comparisons demonstrated that this plant has a strong preference for sciophytic conditions: under strong shade, plants have a higher survival rate, attain a greater height and width, and produce approximately nine times more seeds than in sunny conditions. In contrast with O. kuzinskyanae, published data on O. littoralis indicate that this species occurs in heliophytic conditions. This group of Omphalodes is possibly limited both in geographical distribution and habitat by its vulnerability to hydric stress. Scenarios are discussed that can explain the extensive gap separating the present ranges of the two species and their ecological differences. We propose two new syntaxa: Linario arenariae-Omphalodetum littoralis, Geranio purpurei-Galietum minutuli omphalodetosum kuzinskyanae. © 2015 © 2015 Société botanique de France.


Nimlos M.R.,National Bioenergy Center | Beckham G.T.,National Bioenergy Center | Beckham G.T.,Colorado School of Mines | Matthews J.F.,Biosciences Center | And 3 more authors.
Journal of Biological Chemistry | Year: 2012

Cellulase enzymes often contain carbohydrate-binding modules (CBMs) for binding to cellulose. The mechanisms by which CBMs recognize specific surfaces of cellulose and aid in deconstruction are essential to understand cellulase action. The Family 1 CBM from the Trichoderma reesei Family 7 cellobiohydrolase, Cel7A, is known to selectively bind to hydrophobic surfaces of native cellulose. It is most commonly suggested that three aromatic residues identify the planar binding face of this CBM, but several recent studies have challenged this hypothesis. Here, we use molecular simulation to study the CBM binding orientation and affinity on hydrophilic and hydrophobic cellulose surfaces. Roughly 43 μs of molecular dynamics simulations were conducted, which enables statistically significant observations. We quantify the fractions of the CBMs that detach from crystal surfaces or diffuse to other surfaces, the diffusivity along the hydrophobic surface, and the overall orientation of the CBM on both hydrophobic and hydrophilic faces. The simulations demonstrate that there is a thermodynamic driving force for the Cel7ACBMto bind preferentially to the hydrophobic surface of cellulose relative to hydrophilic surfaces. In addition, the simulations demonstrate that the CBM can diffuse from hydrophilic surfaces to the hydrophobic surface, whereas the reverse transition is not observed. Lastly, our simulations suggest that the flat faces of Family 1 CBMs are the preferred binding surfaces. These results enhance our understanding of how Family 1CBMs interact with and recognize specific cellulose surfaces and provide insights into the initial events of cellulase adsorption and diffusion on cellulose. © 2012 by The American Society for Biochemistry and Molecular Biology, Inc.


Jinkerson R.E.,Colorado School of Mines | Subramanian V.,Colorado School of Mines | Subramanian V.,Biosciences Center | Posewitz M.C.,Colorado School of Mines
Biofuels | Year: 2011

Biofuels derived from algal energy carriers, including lipids, starch and hydrogen, offer a promising, renewable alternative to fossil fuels. Unfortunately, native algal metabolisms are not optimized for the accumulation of these renewable bioenergy carriers. Systems biology, which includes genomics, transcriptomics, proteomics, metabolomics and lipidomics, can inform and provide key insights to advance algal strain development for biotechnological applications. Recent advances in analytical technologies have enabled these sophisticated, high-throughput, holistic 'omics' techniques to generate highly accurate and quantitative datasets that can be leveraged to improve biofuel phenotypes in phototrophic microorganisms. The study of algal genomes and transcriptomes allows for the identification of genes, metabolic pathways and regulatory networks. Investigations of algal proteomes reveal protein levels, locations and post-translational modifications, while study of the metabolome reveals metabolite fluxes and intermediates. All of these systems-biology tools are integral for investigating algal metabolism from the whole-cell perspective. This review focuses on how systems biology has been applied to studying metabolic networks in algae and cyanobacteria, and how these technologies can be used to improve bioenergy-carrier accumulation. © 2011 Future Science Ltd.


Momeni M.H.,Swedish University of Agricultural Sciences | Payne C.M.,Biosciences Center | Payne C.M.,University of Kentucky | Hansson H.,Swedish University of Agricultural Sciences | And 7 more authors.
Journal of Biological Chemistry | Year: 2013

Background: Family 7 cellulases exhibit significant hydrolytic potential in cellulose degradation. Results: Wereport the Heterobasidion irregulare GH7 structure and compare it with other GH7 cellobiohydrolases with simulation. Conclusion: H. irregulare Cel7A exhibits intermediate dynamical and structural properties between Phanerochaete chrysosporium Cel7D and Hypocrea jecorina Cel7A. Significance: These results highlight regions of family 7 cellobiohydrolases important for carbohydrate processivity and association- dissociation rates on cellulose. © 2013 by The American Society for Biochemistry and Molecular Biology, Inc.


Chmely S.C.,National Renewable Energy Laboratory | Kim S.,National Renewable Energy Laboratory | Ciesielski P.N.,Biosciences Center | Jimenez-Oses G.,University of California at Los Angeles | And 3 more authors.
ACS Catalysis | Year: 2013

We employ density functional theory (DFT) calculations and kinetics measurements to understand the mechanism of a xantphos-containing molecular ruthenium catalyst acting on an alkyl aryl ether linkage similar to that found in lignin to produce acetophenone and phenol. The most favorable reaction pathway suggested from DFT is compared to kinetics measurements, and good agreement is found between the predicted and the measured activation barriers. The DFT calculations reveal several interesting features, including an unusual 5-membered transition state structure for oxidative insertion in contrast to the typically proposed 3-membered transition state, a preference for an O-bound over a C-bound Ru-enolate, and a significant kinetic preference for the order of product release from the catalyst. The experimental measurements confirm that the reaction proceeds via a free ketone intermediate, but also suggest that the conversion of the intermediate ketone to acetophenone and phenol does not necessarily require ketone dissociation from the catalyst. Overall, this work elucidates the kinetically and thermodynamically preferred reaction pathways for tandem alcohol dehydrogenation and reductive ether bond cleavage by the ruthenium-xantphos catalyst. © 2013 American Chemical Society.


News Article | January 6, 2016
Site: phys.org

Their fortuitous pairing began shortly after the Chinese-born U.S. citizen and biochemical engineer arrived at NREL in 1992. She came as part of a newly created team tasked by what was then the Energy Department's National Bioethanol Program with exploring a new path for ethanol conversion for biofuels. At the time, global researchers were focusing on using yeast for alcohol production. "That [yeast] organism was the one people had studied for years. We at NREL decided to take a different approach," Zhang said. They chose instead the fermentative bacteria known to scientists as Zymomonas mobilis. "We felt it could be very promising," she said, explaining that the organism could consume glucose very fast—three times faster than yeast—as well as produce ethanol at high yield, which would potentially improve fuel production cost. By tapping that hunger, researchers could use the bacterium to speed up the process of turning the sugars (such as those derived from the long-chain cellulose and hemicellulose found in feedstock) into useable fuels and products. Next, the four-member NREL team successfully engineered the bug for pentose metabolism—pentoses are 5-carbon sugars that have been shown to be less appealing to organisms than 6-carbon sugars such as glucose. Zhang and the team had more positive results. "We ended up with a breakthrough," she said, and their work garnered national attention. In 1995, Science magazine published 'Metabolic Engineering of a Pentose Metabolism Pathway in Ethanologenic Zymomonas mobilis,' and the editors of R&D Magazine named the process a prestigious R&D 100 Award winner. Three cooperative research and development agreements (CRADAs) followed, including a major commitment with DuPont. The NREL/DuPont CRADA covered the entire span of biofuel technology, from biomass to ethanol. Scientists and engineers from DuPont and NREL worked collaboratively for years to further improve the biomass-to-ethanol conversion process, including the biocatalyst development using Zymomonas. Following some additional improvements, DuPont is now in the process of using the technology at their new cellulosic ethanol plant in Nevada, Iowa, where they plan to produce 30 million gallons of biofuels per year from the non-food parts of plants. "I'm pleased to see that kind of dream come true, and proud that the technology could end up in a commercial place," said Zhang, who traveled to the site for the October 30 grand opening of the $225 million plant. In honor of her many contributions, this year Zhang was given the Battelle Memorial Institute Inventor of the Year award as well as the Distinguished Innovator Award at NREL's Innovation and Technology Transfer Awards. At the tech transfer event, the Energy Department's Assistant Secretary for Energy Efficiency and Renewable Energy David Danielson presented her with the award, and she in turn thanked "my dear colleagues, the team that has a lot of talent and has put a lot of effort into this work." Zhang speaks after being named the winner of the Distinguished Innovator Award at NREL's 2015 Innovation and Technology Transfer Awards ceremony. Photo by Dennis Schroeder Her success is no surprise. Zhang, who grew up in a town outside of Shanghai in China, was always a good student. "I liked nature, and I'm good at math and science—but not quite as good in writing," she laughed. During that time, her country was undergoing major social change. When she was in high school in 1977, the government launched China's National College Entrance Examination—known as the gaokao ('big test' in Mandarin)— in an attempt to begin catching up to the rest of the world. She took the second national college entrance exam, a grueling three-day affair administered nationwide in July of 1978. About a month later, a plain letter informed her that she was admitted to East China University of Science and Engineering to study biochemical engineering. She was on her way, and did well in higher education. Following her graduation from East China University in 1982, she was encouraged to take a graduate school entrance exam, which she did—and received another acceptance letter to study at Osaka University in Japan. To prepare, her group underwent a six-month immersion in Japanese language studies. "It was hard, but there are some common characters in both languages, which helped," she said. Then they departed together on a new adventure. "It was my first trip on an airplane, and very exciting," she said, recalling joining about 150 students on a charter from Shanghai to Osaka. To cover basic expenses, she was given a Chinese National Scholarship from 1983 to 1989. Zhang supplemented that by teaching Chinese to Japanese nationals. "I'd get on a moped and drive to the city and teach class for an hour or two, and then come back to the lab to continue the experiments." After earning her Ph.D. in engineering, Zhang spent a year working for the Japanese firm Suntory, researching interferons. As she was looking ahead, political unrest spread in China. The protests and violence that rocked Tiananmen Square in the 'June Fourth Incident' in 1989 forced her to rethink her options. "I was concerned about going back to China, and I couldn't stay in Japan," she said, because her visa wasn't going to be renewed. However, one of her professors was hosting an American academic—who was impressed with her credentials, and invited her to the United States as a postdoctoral student. "I hadn't ever thought about the U.S., but it seemed like a good option," she said. Zhang had studied English, but admitted that her grasp was fairly basic. Following some wrangling for visas, she landed at the University of Michigan in February of 1990 as a research associate. Eventually, when it came time to look for a job, she searched the want ads in professional journals and discovered that an unfamiliar place called NREL was hiring. "I thought it was in North Carolina. Then I received a call from NREL," she laughed. "I didn't have a good grasp of U.S. geography." Still, she applied, interviewed—and was hired. Zhang is now looking at ways to create 'drop-in' biofuels—fuels that could be mixed in directly with jet fuel and other products. She is using Zymomonas to make a four-carbon molecule that is not only potentially a bulk chemical building block, but also can be further chemically converted to produce gasoline, diesel, and jet fuels. Photo by Dennis Schroeder She found a welcoming environment. Zhang has worked alongside a number of key NREL scientists including NREL Research Fellow Mike Himmel, a biochemist whose research on cellulase greatly simplified and lowered the cost of converting biomass to fuel. Her contributions at the lab, too, are notable. "Min has been a pioneer in the field, and has helped establish NREL as a leader since she arrived at NREL in 1992 as part of the Energy Department's then-new National Bioethanol Program," said Acting Biosciences Center Director Mark Davis. Although much of her time originally was spent doing foundational work with Zymomonas mobilis, Zhang hasn't stopped there, and has pushed the frontiers of biofuel research further. While observing a range of outcomes for various biofuels pretreatment processes, she focused on the problems of toxicity in breaking down cellulosic biomass for about four years beginning in 2008. "It had been a black box," she said, but reasoned that "unless we understand why the process is killing our organisms, it would be hard for us to improve [the process]. I decided to explore the black box. This was my mission." Zhang explained that "fermenting lignocellulosic sugars to ethanol is very challenging." In particular, "our organisms didn't like the toxicity—and they died," which prevented using some sugars for high-yield products. Just as she had done early on at NREL, she began systematically analyzing the problem. "I looked at the toxins, and why our [bugs] don't like them." Once she understood more and traced the origins of toxins—whether they were coming from biomass or from the pre-treatment process the engineers used to produce these soluble sugars—she was able to provide feedback to other researchers. Armed with new insight, NREL engineers were then able to make the processes more benign, and researchers were able to find improved organisms. "It gave engineers the context to improve," she said, and the hungry bug thrived in the sugar stream that is derived from the improved pretreatment process. She contributed in other ways to NREL's impact and reach. She has had opportunities to participate in the Energy Department's international program relating with China. As a lab representative on the Department's international bioenergy team, she has traveled to her homeland several times as part of a bilateral partnership in the Advanced Biofuels Forum. Her work has also evolved in the lab. In 2012, with cellulosic ethanol maturing, the Energy Department's Bioenergy Technologies Office was looking in fresh directions, including ways to create 'drop-in' biofuels—fuels that could be mixed in directly with jet fuel and other products. "I started exploring new pathways to produce molecules that can be upgraded to drop-in fuels," she said. Among her promising avenues are examinations with a fatty acid pathway using oleaginous yeast to make long-chain hydrocarbon molecules. Also, she is using Zymomonas to make a four-carbon molecule that is not only potentially a bulk chemical building block, but also can be further chemically converted to produce gasoline, diesel, and jet fuels. The team has made progress, she said: "We've seen exciting results." As she looks to the future, Zhang is proud of where she's been. And she's also pleased that she's been able to partner, so to speak, with various organisms. "Our bug is actually really happy now," she said of her current research and familiar teammate. And that's the way Zhang wants to keep it as she works toward new discoveries. Explore further: NREL teams with Navy, private industry to make jet fuel from switchgrass


News Article | December 22, 2016
Site: www.businesswire.com

SAN DIEGO--(BUSINESS WIRE)--Ligand Pharmaceuticals Incorporated (NASDAQ: LGND) announces it has entered into global license and supply agreements with Novartis for the development and commercialization of a Captisol-enabled oral liquid formulation of trametinib, a kinase inhibitor currently indicated as a single agent or in combination with dabrafenib, for the treatment of patients with unresectable or metastatic melanoma with BRAF V600 mutation. Under the terms of the license, Ligand will be eligible to receive a license fee, royalties on future net sales, and revenue from Captisol material sales. Novartis will be responsible for all costs related to the program. “This represents an expansion of our relationship with Novartis as they develop an oral liquid formulation potential treatment option,” commented John Higgins, Chief Executive Officer of Ligand. “This transaction continues to show the ability of Captisol to address unmet solubility and other formulation issues facing the industry.” Captisol is a patent-protected, chemically modified cyclodextrin with a structure designed to optimize the solubility and stability of drugs. Captisol was invented and initially developed by scientists in the laboratories of Dr. Valentino Stella at the University of Kansas’ Higuchi Biosciences Center for specific use in drug development and formulation. This unique technology has enabled several FDA-approved products, including Amgen’s Kyprolis®, Baxter International’s Nexterone® and Spectrum’s EVOMELA®. There are more than 40 Captisol-enabled products currently in various stages of development. Ligand is a biopharmaceutical company focused on developing or acquiring technologies that help pharmaceutical companies discover and develop medicines. Our business model creates value for stockholders by providing a diversified portfolio of biotech and pharmaceutical product revenue streams that are supported by an efficient and low corporate cost structure. Our goal is to offer investors an opportunity to participate in the promise of the biotech industry in a profitable, diversified and lower-risk business than a typical biotech company. Our business model is based on doing what we do best: drug discovery, early-stage drug development, product reformulation and partnering. We partner with other pharmaceutical companies to leverage what they do best (late-stage development, regulatory management and commercialization) to ultimately generate our revenue. Ligand’s Captisol® platform technology is a patent-protected, chemically modified cyclodextrin with a structure designed to optimize the solubility and stability of drugs. OmniAb® is a patent-protected transgenic animal platform used in the discovery of fully human mono-and bispecific therapeutic antibodies. Ligand has established multiple alliances, licenses and other business relationships with the world's leading pharmaceutical companies including Novartis, Amgen, Merck, Pfizer, Celgene, Gilead, Janssen, Baxter International and Eli Lilly. This news release contains forward-looking statements by Ligand that involve risks and uncertainties and reflect Ligand's judgment as of the date of this release. These include statements regarding clinical development of Captisol-enabled trametinib, the possibility of regulatory approval for a pediatric indication, commercial success, efficacy, potency, competitiveness and the strength of Ligand's product portfolio. Actual events or results may differ from our expectations. For example, there can be no assurance that Captisol-enabled trametinib will progress through clinical development or receive required regulatory approvals within the expected timelines or at all, that further clinical trials will confirm any safety or other characteristics or profile, that there will be a market of any size for Captisol-enabled trametinib or that Captisol-enabled trametinib will be beneficial to patients or successfully marketed. The failure to meet expectations with respect to any of the foregoing matters may reduce Ligand's stock price. Additional information concerning these and other important risk factors affecting Ligand can be found in Ligand's prior press releases available at www.ligand.com as well as in Ligand's public periodic filings with the Securities and Exchange Commission, available at www.sec.gov. Ligand disclaims any intent or obligation to update these forward-looking statements beyond the date of this press release, except as required by law. This caution is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995.


News Article | December 15, 2015
Site: phys.org

Their fortuitous pairing began shortly after the Chinese-born U.S. citizen and biochemical engineer arrived at DOE's NREL in 1992. She came as part of a newly created team tasked by what was then the Energy Department's National Bioethanol Program with exploring a new path for ethanol conversion for biofuels. At the time, global researchers were focusing on using yeast for alcohol production. "That [yeast] organism was the one people had studied for years. We at NREL decided to take a different approach," Zhang said. They chose instead the fermentative bacteria known to scientists as Zymomonas mobilis. "We felt it could be very promising," she said, explaining that the organism could consume glucose very fast—three times faster than yeast—as well as produce ethanol at high yield, which would potentially improve fuel production cost. By tapping that hunger, researchers could use the bacterium to speed up the process of turning the sugars (such as those derived from the long-chain cellulose and hemicellulose found in feedstock) into useable fuels and products. Next, the four-member NREL team successfully engineered the bug for pentose metabolism—pentoses are 5-carbon sugars that have been shown to be less appealing to organisms than 6-carbon sugars such as glucose. Zhang and the team had more positive results. "We ended up with a breakthrough," she said, and their work garnered national attention. In 1995, Science magazine published "Metabolic Engineering of a Pentose Metabolism Pathway in Ethanologenic Zymomonas mobilis," and the editors of R&D Magazine named the process a prestigious R&D 100 Award winner. Three cooperative research and development agreements (CRADAs) followed, including a major commitment with DuPont. The NREL/DuPont CRADA covered the entire span of biofuel technology, from biomass to ethanol. Scientists and engineers from DuPont and NREL worked collaboratively for years to further improve the biomass-to-ethanol conversion process, including the biocatalyst development using Zymomonas. Following some additional improvements, DuPont is now in the process of using the technology at their new cellulosic ethanol plant in Nevada, Iowa, where they plan to produce 30 million gallons of biofuels per year from the non-food parts of plants. "I'm pleased to see that kind of dream come true, and proud that the technology could end up in a commercial place," said Zhang, who traveled to the site for the October 30 grand opening of the $225 million plant. In honor of her many contributions, this year Zhang was given the Battelle Memorial Institute Inventor of the Year award as well as the Distinguished Innovator Award at NREL's Innovation and Technology Transfer Awards. At the tech transfer event, DOE's Assistant Secretary for Energy Efficiency and Renewable Energy David Danielson presented her with the award, and she in turn thanked "my dear colleagues, the team that has a lot of talent and has put a lot of effort into this work." Her success is no surprise. Zhang, who grew up in a town outside of Shanghai in China, was always a good student. "I liked nature, and I'm good at math and science—but not quite as good in writing," she laughed. During that time, her country was undergoing major social change. When she was in high school in 1977, the government launched China's National College Entrance Examination—known as the gaokao ("big test" in Mandarin) in an attempt to begin catching up to the rest of the world. She took the second national college entrance exam—a grueling three-day affair administered nationwide in July of 1978. About a month later, a plain letter informed her that she was admitted to East China University of Science and Engineering to study biochemical engineering. She was on her way, and did well in higher education. Following her graduation from East China University in 1982, she was encouraged to take a graduate school entrance exam, which she did—and received another acceptance letter to study at Osaka University in Japan. To prepare, her group underwent a six-month immersion in Japanese language studies. "It was hard, but there are some common characters in both languages, which helped," she said. Then they departed together on a new adventure. "It was my first trip on an airplane, and very exciting," she said, recalling joining about 150 students on a charter from Shanghai to Osaka. To cover basic expenses, she was given a Chinese National Scholarship from 1983 to 1989. Zhang supplemented that by teaching Chinese to Japanese nationals. "I'd get on a moped and drive to the city and teach class for an hour or two, and then come back to the lab to continue the experiments." After earning her Ph.D. in engineering, Zhang spent a year working for the Japanese firm Suntory, researching interferons. As she was looking ahead, political unrest spread in China. The protests and violence that rocked Tiananmen Square in the "June Fourth Incident" in 1989 forced her to rethink her options. "I was concerned about going back to China, and I couldn't stay in Japan," she said, because her visa wasn't going to be renewed. However, one of her professors was hosting an American academic—who was impressed with her credentials, and invited her to the United States as a postdoctoral student. "I hadn't ever thought about the U.S., but it seemed like a good option," she said. Zhang had studied English, but admitted that her grasp was fairly basic. Following some wrangling for visas, she landed at the University of Michigan in February of 1990 as a research associate. Eventually, when it came time to look for a job, she searched the want ads in professional journals and discovered that an unfamiliar place called NREL was hiring. "I thought it was in North Carolina. Then I received a call from NREL," she laughed. "I didn't have a good grasp of U.S. geography." Still, she applied, interviewed—and was hired. She found a welcoming environment. Zhang has worked alongside a number of key NREL scientists including NREL Research Fellow Mike Himmel, a biochemist whose research on cellulase greatly simplified and lowered the cost of converting biomass to fuel. Her contributions at the lab, too, are notable. "Min has been a pioneer in the field, and has helped establish NREL as a leader since she arrived at NREL in 1992 as part of the Energy Department's then-new National Bioethanol Program," said Acting Biosciences Center Director Mark Davis. Although much of her time originally was spent doing foundational work with Zymomonas mobilis, Zhang hasn't stopped there, and has pushed the frontiers of biofuel research further. While observing a range of outcomes for various biofuels pretreatment processes, she focused on the problems of toxicity in breaking down cellulosic biomass for about four years beginning in 2008. "It had been a black box," she said, but reasoned that "unless we understand why the process is killing our organisms, it would be hard for us to improve [the process]. I decided to explore the black box. This was my mission." Zhang explained that "fermenting lignocellulosic sugars to ethanol is very challenging." In particular, "our organisms didn't like the toxicity—and they died," which prevented using some sugars for high-yield products. Just as she had done early on at NREL, she began systematically analyzing the problem. "I looked at the toxins, and why our [bugs] don't like them." Once she understood more and traced the origins of toxins—whether they were coming from biomass or from the pre-treatment process the engineers used to produce these soluble sugars—she was able to provide feedback to other researchers. Armed with new insight, NREL engineers were then able to make the processes more benign, and researchers were able to find improved organisms. "It gave engineers the context to improve," she said, and the hungry bug thrived in the sugar stream that is derived from the improved pretreatment process. She contributed in other ways to NREL's impact and reach. She has had opportunities to participate in the Energy Department's international program relating with China. As a lab representative on the Department's international bioenergy team, she has traveled to her homeland several times as part of a bilateral partnership in the Advanced Biofuels Forum. Her work has also evolved in the lab. In 2012, with cellusloic ethanol maturing, the Energy Department's Bioenergy Technologies Office was looking in fresh directions, including ways to create "drop-in" biofuels—fuels that could be mixed in directly with jet fuel and other products. "I started exploring new pathways to produce molecules that can be upgraded to drop-in fuels," she said. Among her promising avenues are examinations with a fatty acid pathway using oleaginous yeast to make long-chain hydrocarbon molecules. Also, she is using Zymomonas to make a four-carbon molecule that is not only potentially a bulk chemical building block, but also can be further chemically converted to produce gasoline, diesel, and jet fuels. The team has made progress, she said: "We've seen exciting results." As she looks to the future, Zhang is proud of where she's been. And she's also pleased that she's been able to partner, so to speak, with various organisms. "Our bug is actually really happy now," she said of her current research and familiar teammate. And that's the way Min wants to keep it as she works toward new discoveries. Explore further: NREL teams with Navy, private industry to make jet fuel from switchgrass

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