Jeffrey B. Arterburn - US grants

This proposal outlines a plan to conjugate an organic recognition element and reactive metal complex for the chemical modification of specific biological receptors. The guiding hypothesis for this research is that organoimido rhenium complexes can be designed to bind to an enzyme and chemically modify the active site, preventing catalysis. The organoimido linkage forms a strong, stable covalent bond between the recognition element and a high valent, Lewis acidic rhenium metal center. This metal is capable of coordinating to nucleophilic groups in the active site of the enzyme, thereby affecting catalysis. The specific aims of this project are to synthesize a series of organoimido-rhenium inhibitors of thrombin, measure the inhibition of arginine substrate hydrolysis, investigate the mechanism to develop a model accounting for the inhibition, and then apply the model to design more efficient inhibitors. The thrombin inhibitors will contain a recognition element attached to a rhenium(V) metal center with an organoimido linkage. Recognition elements will match the arginine-binding selectivity of thrombin. A series of inhibitors include flexible and rigid linkages. Different substitution labile ligands will be used to vary the reactivity of the metal center. Enzyme inhibition will be measured using arginine substrates with spectroscopically observable cleavage products. Inhibition will be improved by modifying the recognition element, linkage, and metal center as suggested by mechanistic insight. The resulting thrombin inhibitors may be medically useful for preventing blood clotting. This general approach may also be applied to mechanistically different enzymatic systems and results in new types of inhibitor-based drugs.

This project will develop new synthetic technology for radiolabeling receptor bioligands with technetium (Tc) and rhenium (Re) for diagnostic and therapeutic applications in nuclear medicine. The overall goal of the project is to provide a convenient new method which functions as an "instant kit" and avoids the need for difficult additional chromatographic steps to purify radiolabeled receptor ligands that are required with other methods of radiolabeling. The key conceptual difference of our approaches resides in the use of synthetic polymer-supported bioligands w2hich react with the metal Tc/Re to form organoimido complexes. The project focuses on synthesizing three specific biomedically relevant bioligand-receptor systems: i) biotin for tumors expressing SSTRs; iii) tropane analog for dopamine transporter receptors and the detection and treatment monitoring of Parkinsonian disease. The chemistry of the labeling reaction of these systems will be developed using stable isotope rhenium complexes, which is an accepted surrogate for 99mTc/188Re radionuclides. The structures, chemical properties, and receptor binding affinities of these product complexes will be determined. The polymer supported systems synthesized in this project will be available for labeling studies with 99mTc and 188Re. The successful implementation of this methodology will be a major advance towards t he practical application of Tc/Re radiopharmaceuticals for diagnostic imaging and therapy.

DESCRIPTION (provided by applicant): The long-term objective of this application is to develop effective new antiviral drugs for the treatment of Hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS) caused by the hantavirus. Viruses in the Hantavirus genus, family Bunyaviridae, are high priority Category A viral hemorrhagic fever agents that poses a risk to national security. To date, more than 20 hantaviruses have been described, half of which cause HFRS or HPS. Approximately 150,000 to 200,000 hospitalized cases of HFRS are reported each year throughout the world, with more than half typically occurring in China. The rest are found throughout other parts of Asia, Europe, Russia and Scandinavia. Mortality rates for HFRS vary from 1%-15%, depending in part on which hantavirus caused the infection. The prototype HFRS-hantavirus, Hantaan virus (HTNV), was isolated in 1976 from the lungs of an infected Korean field mouse (Apodemus agrarius). The Sin Nombre virus, the prototype HPS-hantavirus, was first isolated from New Mexico, and has mortality rates of approximately 40%. No licensed vaccines are available for the prevention of HFRS or HPS, and therapeutic efforts are generally limited to supportive care. Our approach for the development of new hantavirus antiviral drugs is guided by mechanistic biochemistry to design and synthesize a series of novel compounds that target the viral replication and transcription pathways. The Specific Aims of this project are 1) to synthesize combinatorial libraries of antiviral drug candidates; 2) to determine the compounds antiviral activity using cell culture and virion-based assays with SNV and HTNV; 3) to conduct systematic chemical modification and in vitro evaluation of resulting change in antiviral activity profile to develop a quantitative structure activity relationship model (QSAR), that will lead to the development of highly active analogs for therapy.

biomedical facility;

[unreadable] DESCRIPTION (provided by applicant): The New Mexico IDeA Network of Biomedical Research Excellence (NM-INBRE) builds upon the Network established through BRIN funding P20 RR16480 to increase the scope of the Science & Research Core (SRC), initiate a new partnership with the National Center for Genome Resources for bioinformatics training and research, and include a new outreach program for students at other 4-year baccalaureate, tribal and community colleges in the state to increase matriculation in graduate biomedical research programs. The organizational structure of the NM-INBRE includes the research intensive doctoral degree granting institutions: New Mexico State University (NMSU) continuing as the lead, and the University of New Mexico (UNM) providing leadership and direction for the Science and Research Core (SRC). The scientific Partner Institutions include Eastern New Mexico University (ENMU), New Mexico Institute of Mining and Technology (NMT), and New Mexico Highlands University (NMHU). The National Center for Genome Resources, a non-profit institution located in Santa Fe, NM will participate in the bioinformatics initiatives. Programmatic activities, outreach, and funding are coordinated through the Administrative Core (AC). The External Advisory Committee (EAC) provides advice and direction for the research and bioinformatics initiatives. The Steering Committee (SC) establishes and enacts programmatic policies for the operation of the network. Research activities are coordinated through the Science Core. The three thematic research areas include: 1) Structure & Function of Biomolecules thematic area (to understand at the molecular level the mechanisms underlying the functions of proteins that mediate critical cellular processes through detailed knowledge of their structures); 2) Cell and Organism (the elucidation of complex physiological processes, such as hypertension, memory, cell division and oogenesis); 3) Pathogens (builds on existing strengths in infectious disease, immunology, inflammation, and a developing biodefense community). [unreadable] [unreadable]

There is tremendous potential for using receptor-targeted technetium-99m radiopharmaceuticals for diagnostic imaging for the detection of cancer, and imaging of neuroreceptors in degenerative diseases such as Parkinson's. This approach also extends to the potential treatment of cancer using the related therapeutic radionuclides Re-186,188. Tc-99m has excellent properties for imaging, and is inexpensive and available at most hospitals. New, more efficient bifunctional chelates are needed to overcome the problems of available ligands for the successful development of receptor targeted radiopharmaceuticals. The linkage must provide a strong connection between the organic substrate and the metal core that is sterically non-intrusive, nonpolar, and does not interfere with the receptor binding affinity or biodistribution. The recent interest in the tricarbonyI-Tc(I) complex has stimulated the search for a ligand system that can be labeled directly in water. This proposal focuses on the synthesis of receptor targeted radiopharmaceuticals based on a novel pyridylhydrazine ligand system that was designed for the tricarbonyI-Tc(I)/Re(I) core. The aims are 1) To synthesize and evaluate (pyridin-2-yl)-hydrazine chelate derivatives (PyHZ-N-chelate) as a new class of bifunctional chelators for receptor targeted tricarbonyI-Tc(I)/Re(I) radiopharmaceuticals. 2) To synthesize PyHZ-N-chelate-Re(CO)3 conjugates of biotin, estradiol, octreotide, and tropane as receptor targeted radiopharmaceuticals. 3) To optimize the radiopharmaceutical properties of the tricarbonyI-Re(I) complexes, and investigate Tc-99m labeling of the receptor targeted (pyridin-2-yl)-hydrazine-N-chelates. The project involves the development of novel heterocyclic substrates for catalytic cross coupling reactions. The completion of these aims will provide a series of important new receptor targeted radiopharmaceutical candidates. These compounds will be optimized to achieve high binding affinities and to exhibit favorable physical characteristics. We will develop experimental conditions for Tc-radiolabeling that are suitable for use in a nuclear medicine clinical environment. The novel compounds and methodology developed in these studies will provide the inertia for establishing a consortium of synthetic chemistry, radiochemistry, and clinical research scientists.

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The purpose of the NM-INBRE program is to strengthen biomedical research in New Mexico's institutions of higher education and to prepare faculty and students for participation in the research programs of the National Institutes of Health. While recognizing the differences that exist among the participating institutions, the program is dedicated to helping create supportive research environments for faculty and students, and facilitating communication and collaborations among these research institutions. The NM-INBRE includes the two research-intensive doctoral degree granting institutions with New Mexico State University (NMSU) as the lead institution and the University of New Mexico (UNM) that is home of the Health Sciences Center and nascent Clinical Translational Science Center. The scientific Partner Institutions include Eastern New Mexico University (ENMU), New Mexico Institute of Mining and Technology (NMT), New Mexico Highlands University (NMHU), and the non-profit National Center for Genome Resources in Santa Fe, NM. The NM-INBRE aims to address the special needs of the biomedical research community in New Mexico. These include the need for strong leadership, guiding scientific progress;opportunities for faculty and student development;facilitation of communication;collaboration between institutions;and the need for availability of bioinformatics for research and education. The main goal of NM-INBRE is to address these needs in order to ensure the continued growth and success of the Network. Programmatic activities, outreach, and funding are coordinated through the Administrative Core (AC). The Steering Committee (SC) implements policies for the operation of the network. The External Advisory Committee (EAC) provides advice and direction for program and research initiatives.

[unreadable] DESCRIPTION (provided by applicant): The New Mexico IDeA Network of Biomedical Research Excellence (NM-INBRE) builds upon the Network established through BRIN funding P20 RR16480 to increase the scope of the Science & Research Core (SRC), initiate a new partnership with the National Center for Genome Resources for bioinformatics training and research, and include a new outreach program for students at other 4-year baccalaureate, tribal and community colleges in the state to increase matriculation in graduate biomedical research programs. The organizational structure of the NM-INBRE includes the research intensive doctoral degree granting institutions: New Mexico State University (NMSU) continuing as the lead, and the University of New Mexico (UNM) providing leadership and direction for the Science and Research Core (SRC). The scientific Partner Institutions include Eastern New Mexico University (ENMU), New Mexico Institute of Mining and Technology (NMT), and New Mexico Highlands University (NMHU). The National Center for Genome Resources, a non-profit institution located in Santa Fe, NM will participate in the bioinformatics initiatives. Programmatic activities, outreach, and funding are coordinated through the Administrative Core (AC). The External Advisory Committee (EAC) provides advice and direction for the research and bioinformatics initiatives. The Steering Committee (SC) establishes and enacts programmatic policies for the operation of the network. Research activities are coordinated through the Science Core. The three thematic research areas include: 1) Structure & Function of Biomolecules thematic area (to understand at the molecular level the mechanisms underlying the functions of proteins that mediate critical cellular processes through detailed knowledge of their structures); 2) Cell and Organism (the elucidation of complex physiological processes, such as hypertension, memory, cell division and oogenesis); 3) Pathogens (builds on existing strengths in infectious disease, immunology, inflammation, and a developing biodefense community). [unreadable] [unreadable]

DESCRIPTION (provided by applicant): Estrogen is a critical hormone in the human body that regulates the growth, development and homeostasis of many tissues. Physiological responses to estrogen include the regulation of mammalian reproduction and breast function, central nervous and immune systems, skeletal physiology and vascular function. We have recently described novel functions of the seven transmembrane G protein-coupled estrogen receptor, GPR30. This receptor is activated by both agonists and antagonists of the classical estrogen receptors, ER1 and ER2. Until recently there were no known specific ligands for GPR30, making traditional pharmacological approaches to the study of this receptor difficult. Our recent studies however have combined both virtual and biomolecular screening to discover the first GPR30-selective agonist, G-1. The specific aims of this application are: 1. Perform a combination of virtual and biomolecular screening to identify additional GPR30-specific ligands based on compounds presently known to bind and activate GPR30. Structure-activity analyses will be carried out to determine the critical molecular determinants for GPR30 binding selectivity and activity as compared to classical estrogen receptors. 2. Based on the biomolecular screening results and structure-activity analyses of Aim 1, rationally design and synthesize small libraries (up to 20 compounds per cycle) of novel G-1-based ligands. The goal of this aim is to separate agonism from antagonism within ligands, and to further evaluate the SAR of novel GPR30 ligands through targeted synthetic chemistry. 3. Characterize the biological functions of the compounds identified and synthesized in Aims 1 and 2. A collection of functional bioassays will be employed to characterize the biological effects of the compounds displaying activity. These assays will include intracellular signaling assays such as calcium mobilization, ERK and EGFR phosphorylation and PI3K activation;more complex cellular assays such as transcriptional activation, cell migration and proliferation;and in vivo studies using mouse models. Understanding the pharmacological profile and structure-activity relationships for ligand binding to GPR30 will be critical to the discovery of novel drugs that target this receptor for the purposes of revealing the underlying physiology of the receptor and developing therapeutic approaches for the improved treatment of estrogen-dependent cancers. PUBLIC HEALTH RELEVANCE: Estrogen plays an important role in normal and disease biology. We have characterized a novel membrane estrogen receptor that likely plays a role in estrogen biology. The goal of this work is to develop novel compounds that can specifically target this new receptor to either activate or inhibit its activity without affecting other estrogen receptors.

The purpose of the New Mexico Idea Network of Biomedical Research Excellence (NM-INBRE) is to strengthen biomedical research in New Mexico's institutions of higher education and to prepare faculty and students for participation in the research programs of the National Institutes of Health. While recognizing the differences that exist among the participating institutions, the program is dedicated to helping create strong, supportive research environments for faculty and students, and facilitating communication and collaborations among these institutions: New Mexico State University (NMSU), University of New Mexico (UNM), Eastern New Mexico University (ENMU), New Mexico Institute of Mining and Technology (NMT), New Mexico Highlands University (NMHU), San Juan College (SJC), Dialysis Clinic Inc. (DCI), National Center for Genome Resources (NCGR). The continuing program will build upon the scientific achievements, increased interactions between investigators, institutional cooperation, faculty and student developmental activities, major strides in bioinformatics analysis and genome sequencing capacity, using the organizational structure and communication infrastructure that have been established. The Specific Aims are: 1. To provide organization, oversight, and leadership for the NM-INBRE Network; 2. To build and enhance the biomedical research base through faculty development and a strong portfolio of scientific research projects in thematic focus areas, and aligned with Signature Programs, Educational and Community focus of the UNM Health Science Center, Clinical and Translational Science Center (CTSC); 3. To build and enhance the biomedical research base through student education, development and participation in the individual research projects; 4. To focus activities of the multi-disciplinary NM-INBRE research network through collaborative bioinformatics and research cores, cooperate synergystically with NCRR IDeA and other biomedical and health related programs at the state, regional and national level. These efforts will engage our diverse student population into a cohesive network of undergraduate, and graduate training programs that provides a pipeline of trainees for the State's basic, translational and clinical research career opportunities.

DESCRIPTION (provided by applicant): The genus Flavivirus, comprising 80 species of single-stranded, positive-sense RNA viruses, includes a large number of globally significant emerging pathogens. In the last 50 years many flaviviruses, such as dengue, West Nile, and tick-borne encephalitis viruses, have exhibited dramatic increases in incidence, disease severity and/or geographic range. For example the annual number of cases of dengue hemorrhagic fever cases worldwide has risen from nearly 0 in the 1950's to 500,000 today. These trends are exacerbated by failure of vector control to limit virus spread as well as the absence of vaccines for viruses such as dengue and West Nile. Thus effective antiviral therapies are urgently needed to ameliorate the disease burden imposed by flaviviruses. At present, however, no licensed therapies are available for any flavivirus, largely because existing broad-spectrum drugs have failed to show efficacy against flaviviruses or have generated unacceptably high levels of toxicity. To overcome these limitations, it will be necessary to develop not only new antiviral drugs but also innovative strategies to lower their effective dose and thereby mitigate toxicity. The recent discovery that certain FDA-approved fluoroquinolone antibiotics enhance the activity of the RNA interference pathway suggests one promising new strategy. RNA interference is a ubiquitious antiviral defense of eukaryotes that acts by targeting small interfering RNA's (siRNA's) to complementary regions in the viral genome; genomes bound to siRNA's are marked for cleavage and degradation. Because binding of siRNA's to a target sequence requires nearly perfect complementarity, RNAi imposes selection pressure for viral mutation that disrupts such complementarity. The proposed research will test the hypothesis that enhancing RNAi will amplify the effect of mutagenic nucleoside analogs on dengue virus mutation rate and replication, and that the synergistic effect of RNAi enhancement will accelerate lethal mutagenesis driven by nucleoside analogs. If this hypothesis is correct, the finding of this study will represent a significant advance in the development of new therapies for flaviviral disease.

The NM-INBRE DRPP provides critical support for promising new and early career investigators, and is a determining factor in the direction of their developing research careers. These projects address significant biomedical questions and critical health problems in the areas of Brain and Behavioral Health; Cancer; Cardiovascular and Metabolic Diseases; Child Health; Environmental Health; Infectious Disease and Immunity. The quality of the DRPP science is outstanding, resulting in publications in high impact journals, and pending patents for novel pancratistatin and rigidin analogues with anticancer properties. Efforts to encourage research collaboration have been successful, during the current funding period 23% of the publications have involved collaborations between 2 or more NM-INBRE participants, and this trend is expected to increase in the continuing program. Investigators have been successful in competing for external federal grants, in spite of the difficult funding environment, including recent R01, R21, R03, and R15 awards. The DRPP has made significant impacts on the partner institutions, such as San Juan College, a two-year associate degree-granting institution in the four-corners region with a large Native American student population, where the research activity supported by the NM-INBRE was leveraged to justify a competitive application for an NSF grant to remodel the research space and install a clean room that was funded and now supports research projects. The framework of DRPP projects also serve the primary objective of exposing students to research experiences, and this impact will continue with increased opportunities through an expanded portfolio of projects.

DESCRIPTION (provided by applicant): The New Mexico idea Network of Biomedical Research Excellence (NM-INBRE) is a statewide network that promotes biomedical and community based research and training. The organizational structure of the NMINBRE includes New Mexico State University (NMSU) as the lead institution, with research-oriented research-intensive doctoral degree granting programs at this institution and at both the University of New Mexico (UNM) main campus and its Health Sciences Center (HSC). The scientific partner institutions include Eastern New Mexico University (ENMU), New Mexico Institute of Mining and Technology (NMT), New Mexico Highlands University (NMHU), Western New Mexico University (WNMU), Northern New Mexico College (NNMC), San Juan College (SJC), the National Center for Genome Resources (NCGR), and the Pueblo of Zuni community. Having established an effective organizational structure and institutional cooperation with recognition of each partner's important and unique roles, the continuing program will build upon its scientific achievements, effectively integrate training and research using bioinformatics and next generation technologies, connect new investigators with established mentors and collaborators, and contribute to developing New Mexico's biomedical research workforce. The Specific Aims are: 1. To provide organization, oversight, and leadership forth NM-INBRE Network; 2. To provide student-focused training and research experiences; 3. To provide a collaborative sequencing and bioinformatics core that supports hypothesis and discovery-driven research in the thematic research areas of the New Mexico INBRE; 4. To build and enhance the biomedical research base through faculty development and a strong portfolio of scientific research projects in the thematic research areas. 5. To support multi-disciplinary collaborative and community-based research, and cooperate synergistically with the NIGMS IDeA and other biomedical, health related, and workforce development programs at the state, regional and national level. These efforts will result in productive biomedical research teams, supportive research environments, and a cohesive network for training students to enter careers in basic, translational. Clinical and community based research.

The PI is an experienced leader managing a comprehensive Administrative Core with an accomplished staffed who have effectively developed and promoted the NM-INBRE network. The AC maintains expansive oversight of the overall program through an effective organization structure employing active roles of steering and external advisory committees to effectively govern the program, with representative and input from all of the participating network institutions. The AC program evaluation monitors and assesses all aspects of the program to determine progress and feedback for further refinement to optimize program implementation and meet the needs of network participants. These activities are conspicuous in the management and oversight of the developmental research project program, mentoring program, bioinformatics core, and activities that provide opportunities for student research experiences, where the effective recruitment and involvement of faculty and students from the partner institutions are cardinal principles.

With this award, the Chemical Measurement and Imaging Program in the Division of Chemistry is funding Professors Jeffrey Arterburn, Charles B. Shuster, and Tanner Schaub of New Mexico State University to develop methods for labeling unsaturated lipids in the membranes of living cells with fluorescent dyes. To meet this challenge, a combined approach involving catalytic cross-metathesis coupling chemistry, live cell imaging and ultrahigh resolution mass spectrometry will be used. The aims are to synthesize useful lipid probes for imaging, and then characterize the labeling chemistry within the biological context of the cell membrane. The interdisciplinary methodology and research environment are well suited to the education of scientists at all levels, and continue the PI's efforts to promote participation of women and underrepresented minorities in science. The methodology will be employed outside the University setting in a boot camp for science journalists. The team will develop displays featuring "Chile Chemistry" to introduce chemistry and scientific principles to elementary school students during tours of the NMSU Chile Pepper Institute.

The identity and distribution of labeled lipids will be determined by ultrahigh resolution mass spectrometry and their localization and dynamic motion will be imaged using optical microscopy. The strategy of chemically modifying native unsaturated lipids by fluorescent dye attachment to produce optical imaging probes is new and complementary to existing strategies that utilize exogenous probes, bioorthogonal labeling, and direct spectroscopic methods to study membrane lipids. Aim 1 will optimize chemistry to synthesize useful lipid probes for live-cell imaging, evaluate metabolic alterations to the lipid probes, and label lipid extract mixtures to characterize the composition of unsaturated lipids as a basis for comparative analyses. Aim 2 will label specific lipids in live cells to investigate biological context of the cell membrane as a factor in selectivity. Additionally, the identity and distribution of dye-labeled lipids will be determined by ultrahigh resolution mass spectrometry and their localization and dynamic motion will be tracked by optical imaging. Aim 3 will use advanced fluorescence microscopy experiments to assess the membrane localization and the functionality of the CM-labeled lipids through short and long term observations. In the long term, the realization of this labeling methodology will provide a powerful analytical approach for fundamental studies of lipid localization, dynamics and determining the roles of discrete lipids in membrane biology.

? DESCRIPTION (provided by applicant): Hormonal therapies have led to great improvements in the survival of women with estrogen receptor (ER)-positive breast cancers. However, residual tumor cells often become resistant to anti-estrogen treatment resulting in recurrences that are frequently more aggressive than the original cancer. Current ER- targeted hormonal therapies include selective estrogen receptor modulators (e.g. tamoxifen, raloxifene), pure antagonists (e.g. fulvestrant) and aromatase inhibitors, all of which can result in resistance following prolonged/chronic use. In addition, women taking SERMs also experience an increased incidence of endometrial thickening/hyperplasia, polyps and cancer. Multiple mechanisms have been described yielding these deleterious effects; however, most recently the 7-transmembrane spanning G protein-coupled receptor GPER has been demonstrated to contribute to both hormonal resistance and off-target effects in the uterus. This conclusion is supported by the fact that anti-estrogens act as agonists for GPER and that GPER activates growth factor receptor pathways that are important in hormonal resistance. In our previous work, we have discovered and characterized novel selective ligands for GPER that do not bind ER? or ER?. To date however, there are no known ligands that exhibit the inverse selectivity. Towards this overall goal, we have identified a family of novel small molecules that are highly selective for ER? and ER? vs. GPER. As estrogen and current anti-estrogens cannot distinguish between ER?/? and GPER, our newly identified small molecule provides the opportunity to create novel ligands and therapeutic agents to selectively manipulate and target classical ERs. Our hypothesis is that through selected chemical modifications to this first generation ER?/?-selective compound, we will optimize the overall affinity, receptor selectivity and agonist/antagonist profile with the ultimate goal of creating a truly ER?-selective antagonist. The specific aims of this proposal are 1. To design and synthesize a suite of derivatives based on our highly ER?/?-selective scaffold; 2. To evaluate and prioritize these compounds in vitro for receptor binding, cellular activation/inhibition of rapid and genomic pathways, cell proliferation and toxicity and 3. To determine the ability of compounds to modulate estrogen-dependent physiology in vivo, particularly the anti- tumor properties of lead compounds in mice bearing ER-dependent and anti-estrogen-resistant xenograft, orthotopic and PDX tumors. The successful completion of these aims should result in a better understanding of the ligand selectivity of ER?, ER? and GPER, the identification of innovative compounds that provide novel pharmacological tools for the study of estrogen biology and (patho)physiology, and, with their successful application in the clinic, reductions of the development of anti-estrogen resistant recurrences of breast cancer and off-target effects in the endometrium, ultimately enhancing survival and the quality of life of women with breast cancer.

An award is made to New Mexico State University to acquire an Orbitrap Fusion mass spectrometer, to be housed in the Chemical Analysis and Instrumentation Laboratory. This instrumentation is the state-for-the art for chemical characterization of extremely complex mixtures and will be used in a wide variety of applications that range from alternative fuel research to disease research and fundamental biology. This instrument will be used to describe the chemical composition of complex mixtures to help improve the manner in which biomass is cultivated and processed into fuel and will be a key component to multiple health-related research projects including the imaging of live cells. Given the wide range of applications where the instrument will be used, this research will generate both novel applications and significant advancements in the application of this technology. Finally, the collaborative research projects that use the Orbitrap Fusion will provide a framework for discovery that will improve the ability of our institution to recruit and retain excellent faculty and will provide enormous opportunity for student participation in science and engineering.

The purpose of this acquisition is twofold. First, this acquisition will enable mass spectrometry-based proteomics for a number of collaborative research projects. Modern proteomic capability is currently absent in the state of New Mexico. The Orbitrap Fusion instrument architecture includes three orthogonal fragmentation techniques (electron transfer dissociation, collisional dissociation and higher energy collisional dissociation) and multiplex-in-time ion fragmentation capability, all of which are critical for modern quantitative proteomics and the analysis of protein post-translational modification. Second, with respect to multiple current research efforts in energy, environment and lipid applications, the Orbitrap Fusion offers excellent mass accuracy, ion transmission efficiency across a broad mass range and high resolving power for complex mixture analysis with collisional and higher energy collisional fragmentation methods to aid structural elucidation. Within those project areas, we will utilize the Orbitrap Fusion for the analysis of bio-oils and fuel precursors from biomass thermotreatment and upgrading, algal growth media and feedstocks, lipid mixtures from various biofuel feedstocks and complex environmental samples.