Category: Elliott, Sean
Dr. Sean Elliott Receives 4 Year National Institute of Health Grant to study “Structure, Function and Diversity in the Bacterial Cytochrome c Peroxidase Family”
The new grant will enable studies in the Elliott Group to dissect the way in which nature has made use of a common motif of bioinorganic chemistry, the iron-bearing structure known as a c-type heme, and to utilize it for diverse chemistry. While Elliott has a long-running interest in heme and redox chemistry, here the group studies the titular ‘bacterial cytochrome c peroxidase’ (or, bCCP) family of enzymes. While prototypical bCCPs are found in gram negative microorganisms where they detoxify endogenous or exogenous hydrogen peroxide (H2O2), the Elliott group has realized that there exist in microbes novel bCCPs which engage in unknown chemistry. In the work sponsored by the NIH, the Elliott group will use a combination of biochemistry, electrochemistry, spectroscopy and structural biology to elucidate the bCCPs found in under appreciated microbes, and attempt to rationalize why the enzymes work as they do.
The work to be supported is a team effort where the enzymes discovered and produced in the Elliott Group will be examined here at BU, but also in collaboration with structural biologists at MIT and spectroscopists at Carnegie Mellon and the University of Michigan.
As bCCPs are enzymes on the front-line of the native defenses of NIH Select List pathogens including Pseudomonas aeruginosa, Burkholderia complex species, Vibrio cholerae, Campylobacter jejuni, and Yersinia pestis, these studies will provide fundamental insight into the long-term development of new antimicrobial compounds that will target the novel features of bCCP structure.”
Dr. Elliott, who is also a two time recipient of the Scialog® Award Research Corporation (2010-2011), and received the 2007 Gitner Award for Distinguished Teaching in 2007 and an NSF CAREER Award in 2005 (among other honors), works with the Elliott Research Group to investigate the interplay between biological systems and redox-active species (e.g., metal ions, organic radicals, disulfide bonds, reactive oxygen species). Their emphasis is on the kinetic and thermodynamic basis for catalytic redox chemistry, as well as the molecular basis of how nature tune redox cofactors do the hard work of Life.
Professor Sean J. Elliott was recently awarded 4 Years of funding from the National Institute of Health for his proposal entitled: Redox Reactions of the AdoMet Radical Enzyme Superfamily.
The new grant will fund research into the oxidation/reduction chemistry of enzymes that belong to the AdoMet Radical Enzyme (ARE) superfamily. The ARE superfamily makes use of an unusual iron-sulfur cluster and S-adenosyl methionine to achieve a diverse array of chemical transformations. This research is relevant to human health, as AREs are important enzymes in the production of natural products that can serve as drug molecules. The project will provide insights into the fundamental processes of ARE function , and provide a new view in how similar enzymes achieve diverse chemistry.
Congratulations to Professor Elliott and his group on earning this award. For more information about Dr. Elliott and his research please visit his faculty page.
The Chemistry Department is one of the most active research departments at Boston University. With 24 research active faculty involved in many different focus areas, we are committed to a research active learning environment where our faculty and students are afforded the opportunity to do cutting edge chemical research. In order to continue to build on our strong research focus, our faculty have submitted over 30 grant proposals during the 2015-2016 academic year, with 20 of them being awarded totaling over $5 million in new funding this year alone.
Below is a list of the awarded grant proposals as well as their abstracts. For more information about the Faculty member who will the the Principal Investigator please click on their name.
Boston University Chemistry Department Awarded Grants Academic Year 2015-2016
Scott Schaus, National Institute of Health / National Institute of General Medical Science
Enantioselective Catalytic Boronate Reactions
The development of new chemical methodologies is an important objective of organic synthesis. An area that continues to inspire chemists is the chemistry of organoboranes and boronates. The unique properties of boron and the ability to activate organic boronates to deliver carbon nucleophiles has yielded an impressive array of chemical methods and processes. We will extend the ability of organoboranes and boronates to deliver carbanion equivalents in novel condensation reactions including chemoselective carbonyl condensations and multicomponent reactions. The reactions will be rendered asymmetric through the development of asymmetric catalysts and chiral boronate reagents and the utility of the methods developed demonstrated by the asymmetric synthesis of pharmaceuticals and natural products. Significant advances have been made in the mechanistic understanding of boronate activation via ligand exchange with chiral diols. We will use the mechanistic insight we have obtained to expand the repertoire of reactions catalyzed by dynamic ligand exchange processes to include acyl cyanides as electrophiles, borono-Petasis reactions, and ortho-quinone methide chemistry. Our continued interest in reaction discovery has led to the identification of chiral diol acid catalysts capable of promoting the enantioselective addition reactions to acetals. We seek to explore this reactivity and expand it to include types of functionalized nucleophiles in additions to oxoniums and iminiums and boronate hetero-Diels–Alder reactions. Goals of the research program include developing a breadth of reactivity, providing access to novel chiral blocks, and new reaction development. Bond constructions are selected to access chiral synthetic intermediates that could be used in the construction of pharmaceuticals and natural products. The results will transform the way boronate nucleophiles are utilized in enantioselective synthesis.
John Straub, National Institute of Health
Probing the role of membrane and cholesterol on APP-C99 structure and dynamics
Aggregation of proteins of known sequence is linked to a variety of neurodegenerative disorders. Familial mutations in the Amyloid Precursor Protein (APP), from which the amyloid β (Aβ) protein associated with Alzheimer’s Disease (AD) is derived, have been linked with the early onset of amyloid disease.
With this computational and theoretical research grant, augmented by synergistic experimental research collaborations, we will determine the structure and dynamics of the 99 amino acid transmembrane fragment of APP (APP-C99) in membrane environments in order to address fundamental biophysical questions articulated in three Specific Aims. (1) We will explore how length, sequence, and membrane composition influence the structure of the APP-C99 monomer. (2) The structures of APP-C99 dimers and the associated stability as well as the monomer-dimer equilibrium are also influenced by membrane composition and C99 sequence. We will investigate the influence of these environmental factors on the structure and dynamics of dimer formation. (3) We will also determine how APP-C99 interacts with cholesterol and cholesterol-analogs, as well as how those interactions influence APP-C99 structure and dimerization.
Plasmonically Enhanced Stimulated Coherent Spectroscopy
There is growing interest in using plasmonics to enhance and control chemistry on surfaces for applications such as chemical catalysis, pollution mitigation and energy conversion. The proposed time-domain experiments are aimed at developing a better dynamical and structural description of how molecules interact with plasmonic materials. Differences in energy fluctuation timescales, interaction strengths and energy distributions are anticipated for molecules on plasmonic surfaces as compared to molecules in liquid solutions. Characterizations of these properties are central to understanding chemical activity occurring on these substrates. Plasmonically enhanced stimulated coherent vibrational and electronic spectroscopic measurements of analytes on plasmonic substrates will be obtained to learn about these interactions. Fabricated metal nanoparticle cluster arrays will be employed here. This substrate type provides a wide range of design parameters that will be used to maximize signal strengths and robustness for the planned studies. The proposed research effort will be carried out by two Boston University PIs with complementary expertise in ultrafast spectroscopy and nanoscience.
Tom Tullius, National Science Foundation
Chemical probing of RNA tertiary structure in a whole transcriptome at single‐atom resolution
RNA (ribonucleic acid) is now widely appreciated to be a key participant in nearly all of the activities of the cell, yet we have limited information on the three-dimensional structures of most RNA molecules. This presents a challenge, because we know that the biological function of an RNA molecule depends on its structure. To understand the relationship between structure and function for the large number of RNA molecules that populate the cell, new high-throughput experimental approaches for structure determination are needed. The aim of this project is to develop a new experimental method that can provide detailed information on the three-dimensional folding of all the RNA molecules in a cell, in one experiment. The new method combines chemical probing of RNA structure by the hydroxyl radical, the quintessential Reactive Oxygen Species, with analysis by high-throughput sequencing, so that the structures of all RNA molecules in a cell can be monitored simultaneously.
John Porco, National Institute of General Medical Science
Chemical Synthesis of Complex Natural Products for Translational Science
The National Institutes of Health, Institute of General Medical Sciences (NIGMS), has awarded Professor John Porco and coworkers (http://sites.bu.edu/porcogrp/) a five year MIRA (R35) grant entitled “Chemical Synthesis of Complex Natural Products for Translational Science.” The Maximizing Investigators’ Research Award (MIRA-R35), an Outstanding Investigator Award, is a grant that provides support for all of the research in an investigator’s laboratory that falls within the mission of NIGMS. Within these bounds, investigators have the freedom to explore new avenues of inquiry that arise during the course of their research. The goals of the MIRA (R35) research program are to continue chemical syntheses of bioactive molecules and expand efforts and capabilities in translational science. The MIRA effort effectively replaces two previous NIGMS-funded RO1 grants (Biomimetic Synthesis of Complex Natural Products (GM-073855) and Chemical Synthesis of Bioactive Flavonoid and Xanthone-Derived Natural Products (GM-099920) which were highly productive and led to 41 publications from 2010 – 2015. As part of the MIRA project, the Porco group will continue development of novel synthetic methodologies for concise entry to bioactive classes of natural products including oxaphenalenones, meroterpenoids, polyprenylated acylphloroglucinols, tetrahydroxanthones, and dimeric chromones. The project will also continue major emphasis on collaborations to study biological properties and mode of action (MoA) of target molecules for ultimate use as pharmacological therapies for human cancers as well as viral and bacterial illnesses.
Malika Jefferies-EL, National Science Foundation
Early Career Investigator Workshop
In an effort to develop the next generation of Chemistry researchers, the National Science Foundation Division of Chemistry has sponsored the proposal of Professor Malika Jeffries-EL and co-PI Jeff Moore for the University of Illinois-Urbana Champagne to hold an NSF Chemistry Early Career Investigator Workshop. The objective of these workshops is to provide early career chemist with networking opportunities and relevant information needed to better assess their research ideas, projects, and plans so as to more effectively compete for grant applications to the NSF CAREER program, other NSF programs and other federal agencies. The workshop was held March 10th-11th 2016 in Arlington VA at the Hilton Garden Inn, which is close to the NSF headquarters, enabling the participation of many program officers. The workshop is had approximately 120 participants and will be open to investigators performing research in NSF-supported disciplines within the United States. While the workshop is primarily intended for junior faculty members, advanced graduate students, postdocs, and other research scientist.
Ksenia Bravaya, Boston University
Patrick Mclellan Leavitt Research Award
This award is designed “to support research of one or more non-tenured junior faculty members, or graduate students, in chemistry or biology at the College of Arts and Sciences. Preference shall be given to female faculty who demonstrate a commitment to encouraging women to study science, or to female graduate students.”
Dr. Bravaya will use these funds to support her research into challenging electronic structure phenomena in biomolecules and systems relevant for materials, which include photoinduced processes, autoionizing electronic states, and magnetic field effects. This award will help her and her team use and develop high-level electronic structure methods targeting processes involving multiple electronic states, chemistry of open-shell species in magnetic fields, and electronically excited and metastable systems.
Mark Grinstaff, National Science Foundation
SusChEM: Glycerol Polycarbonates as New Biomaterials
The future development of medical devices. Scientific advances, such as those described in this NSF sponsored research, will support US industries, which play an important role in this medical polymers market estimated to exceed $3.5 billion by 2018. This grant support undergraduate students and graduate students, who will benefit from an interdisciplinary cutting-edge research and educational experience that encompasses training in biomaterials and polymer chemistry. Students will be encouraged to think independently and creatively while recognizing the importance of collaborating with other experts (e.g., materials scientists, pathologist, biomedical engineers, and patent lawyers). These activities will contribute to positive societal outcomes by fostering excitement for basic research while educating and training a future workforce.
In the biomaterials and biomedical field, degradable polymers such as poly(lactic acid) and poly(glycolic acid) are widely studied and are an integral component of many medical device products. Although extensively used, these poly(hydroxy acid)s possess a number of limitations including: 1) limited capability for backbone functionalization; 2) acidic products upon degradation; and 3) poor control over molecular weight and dispersity. Consequently, there is significant need for new polymeric biomaterials that are amenable to facile modification, multiple processing or manufacturing methods, and controlled degradation without the generation of a local acidic environment. With NSF funding, the PI (Grinstaff) and his team will design, synthesize, and evaluate of a novel class of natural metabolite-based, non-toxic, and biodegradable polymeric materials based on a polycarbonate of glycerol. The activities in this highly interdisciplinary and cutting-edge research environment will also afford educated and trained undergraduate and graduate students for employment in industry and academia.
Mark Grinstaff, Samsung
Basic Research on New Ionic Liquid Electrolytes: Synthesis
This basic science research project directed by Professor Grinstaff investigates his interest in new ionic liquids as potential electrolytes for Li ion batteries. Given his interest and past publications, Samsung has reached out to sponsor this project. Specifically, the Grinstaff laboratory will synthesize a small library of 10 new phosphonium and piperdium ionic liquids. We will mix these ionic liquids with differing Li salts and characterize the thermal properties, viscosity, conductivity, and electrochemical window of these electrolyte compositions.
Mark Grinstaff, MIT/Comm. Of Mass
Translation of a Hydrophilic Coating for Latex Condoms: The HydroGlide Coating
The HydroGlide Coating is a novel and stable hydrophilic coating on latex condoms that can maintain its lubricity when in contact with water. This technology will promote consistent and proper condom usage, while improving user satisfaction. The goal is to translate this novel latex coating technology to the market through collaboration with Biocoat Incorporated who will optimize this coating prototype towards one that is adaptable towards large-scale manufacturing under GMP.
Bjoern Reinhard, Millipore
Plasmonic Nanofilters For Viral trapping and inactivation
This award will go towards research into creating plasmonic metamaterials to develop a novel class of photonic filters that are capable of selectively trapping and inactivation of viruses. Several complementary technology developments, ranging from state-of-the-art electron-beam lithography, fabrication methods combined with simulation and design will be aimed at developing 21st century adaptive filters for biopharmaceutical applications. Evaluation of the Optical gradient forces in fabricated membranes will be combined with multi-physics modeling that include both plasmonics and hydrodynamics. Experiments on fluid feed materials and virus systems selected by EMD will be performed to characterize selective trapping. Data will be shared openly between BU and EMD, under NDA. An assessment of manufacturability, scalability will be performed in close consultation with engineers and scientists at EMD.
Bjoern Reinhard, BMC Corp.
Nanoplasmonic Metamaterial Filters
This project explores the mechanism underlying virus inactivation through laser irradiation.
Bjoern Reinhard, National Cancer Institute
Illuminating Dynamic Receptor Clustering in the Epidermal Growth Factor Receptor
Dysregulation of members of the epidermal growth factor (EGF) receptor (EGFR) family is associated with oncogenesis and tumor growth. Due to its relevance in cancer development, EGFR is an important target in cancer drug discovery, and several EGFR targeted therapies have already been developed. Their clinical success has, however, often been modest, reinforcing the need for a more complete understanding of the EGFR signaling pathway. This proposal focuses on the insufficiently understood role of large-scale EGFR associates (“clusters”) in signaling initiation and transduction, in particular. While it has long been known that ligand induced dimerization plays a critical role in receptor signaling, there is growing evidence that this textbook model needs to be augmented to account for the heterogenous lateral distribution of the receptor in the plasma membrane. The local enrichment of the receptors in ”micro-domains” or ”nanoclusters” could strongly affect cooperative receptor interactions and shift the local EGFR association equilibria through a local concentration effect. The experimental investigation of the fundamental mechanisms underlying the large-scale receptor organization with conventional fluorescence microscopy remains challenging, due to the method’s limitation with regard to throughput, spatial and temporal resolution, and maximum observation time. Plasmon Coupling Microscopy (PCM) is a novel non-fluorescence based approach that uses electromagnetic interactions between noble metal nanoparticles (NPs) to investigate receptor clustering on subdiffraction limit distances (but beyond the spatial barrier o Fluorescence Resonance Energy Transfer, FRET). NP’s do not blink or bleach, are very bright, and can be imaged in a conventional widefield microscope. Consequently, PCM facilitates the monitoring of EGFR clustering without limitations in observation time in many individual cells simultaneously. This competitive renewal builds upon the plasmon coupling based tools developed in the previous funding cycle and outlines a vigorous research plan to elucidate the structural origin of dynamic EGFR clustering. PCM will then be applied to test the hypothesis that receptor clustering regulates the mode and strength of signaling and to elucidate the mechanisms underlying a spatial regulation of signaling intensity and outcome. The obtained insight will improve the understanding of spatial regulation mechanisms for a broad range of receptors. Noble metal NPs are not only superb optical labels for characterizing EGFR clustering in the plasma membrane, but they also represent potential therapeutic tools to restore and enhance negative EGFR signaling after covalent attachment to EGF. This hypothesis is experimentally tested in this proposal. If successful, this strategy would provide a new approach for overcoming apoptosis evasion in cancer.
Research For Undergraduates Program: Chemistry Research Addressing Biological Problems
This REU site will afford 30 undergraduates (10 per summer) the opportunity to engage in cutting edge, basic chemical research projects that address biological problems. REU students can choose from among 24 groups in BU’s Departments of Chemistry, Biology, or Biomedical Engineering. They will work in newly renovated laboratories, have access to the synthetic and computational resources of BU’s leading research centers, and be trained on state-of-the art instrumentation. The goal of the program is to provide undergraduates from 4-year colleges and community colleges who have limited or no research opportunities at their home institutions with an intensive, interdisciplinary research experience. At least 50% of the participants will be from community colleges with no research opportunities at their home campuses. The demographic aim is to have at least 70% of the students to be underrepresented minorities and at least 50% to be women. The program will also give preference to veterans applying from the target institutions. By fully integrating the REU students into the daily life of the laboratories and through mentoring by faculty, graduate students, and postdoctoral research associates, the REU students will fully experience the breadth of chemistry research and be motivated to pursue careers in science.
Mark Grinstaff, L-Oreal
Poly-amido-saccharide (PAS) Biomaterials for Cosmetic and Beauty Applications
This project will explore a new class of polysaccharides, recently reported, for their properties as new materials as well as their biological activity in anti-ageing and/or preservatives and/or photoprotection and/or depigmentation.
Aaron Beeler, National Science Foundation CAREER
Chemical Transformations Enabled by Flow Chemistry
This award funds specific projects that are integral to the long term development of the Beeler Research Group. The overarching objective of our research is synthesis of small molecules that are used as tools to study human diseases. To achieve these goals we have identified a number of reactions that are highly enabled by flow chemistry. The scientific projects outlined in this proposal will result in sigfnificant advances toward the synthesis of a number of important biologically active molecules. Furthermore, the projects will provide advancements in flow chemistry that will enable chemists in acadmia and industry to implement a number of challenging reactions. The education projects in the proposal will provide training for undergraduates in flow chemistry, which is emerging as a critical technology in industry. The outreach projects will provide high school students from a wide range of socioeconomic backgrounds with a foundational path toward STEM higher education and careers. The first Aim is focused on expanding the utility of our flow photochemistry platform to develop reactions that will be highly useful in synthesis and medicinal chemistry. The second Aim is to develop a platform that is capable of milligram to multigram scale electrochemical reactions in flow. The third Aim will utilize highly reactive diazoalkanes in a Buchner reaction to access complex scaffolds. The proposal also outlines our continued involvement in outreach and education, including the Upward Bound program at Boston University to educate local high school students in chemistry, developing a summer camp for high school students, and integrating flow chemistry into the undergraduate laboratory curriculum.
Debbie Perlstein, National Science Foundation CAREER
Elucidating the role of ATP in cytosolic iron sulfur cluster biogenesis
Dr. Perlstein’s research focuses on how metals are mobilized and monitored within the cell so that they get to where they need to go and do not end up in places they shouldn’t. With this new five-year grant, Dr. Perlstein plans to unravel the molecular mechanism by which iron-sulfur cluster cofactors are assembled in the cytosol of eukaryotic organisms. Since inhibition of this first step in cluster biosynthesis can lead to defects in DNA replication, DNA repair and protein synthesis, she expects this work will provide new insight into how cluster biogenesis affects these other fundamental biochemical pathways.
With the CAREER award, Perlstein also plans to develop new undergraduate course curriculum as well as building on current STEM outreach program efforts to begin training the next generation of scientists.
Mark Grinstaff, Brigham & Women’s
Efficacy and Safety of a Novel, Implantable Drug-Eluting Film in Sarcoma
Despite aggressive multimodality therapies combining surgery, radiation, and/or chemotherapy, mesothelioma is essentially a universally fatal cancer with the majority of patients succumbing to local recurrence. To date, there is no effective cure for this disease or means to prevent recurrence. Consequently, new approaches, biomaterials, and mechanisms to deliver pharmacologically active agents are needed. In the current proposal, we utilize a murine model of human mesothelioma to investigate a new approach to reduce intracavitary tumor recurrence with the delivery of chemotherapy via unique tumor localizing polymeric nanoparticles (NPs) administrated locally at the time of surgical resection. The particle localizes to tumor in situ where upon endocytosis these “expansile” nanoparticles (eNPs) undergo a pH dependent transformation and swell from 100 nm to 1000 nm in diameter thus releasing the encapsulated chemotherapeutic agent intracellularly and acting as a drug depot, or reservoir, to deliver high local drug concentrations. Uniquely, expansion of eNPs also results in a functional depot whereby subsequently delivered intracavitary chemotherapy is concentrated inside eNP with prolonged delivery in situ at the sites of tumor where eNP accumulate. This is in contrast to conventional polymer delivery systems that degrade (e.g., poly(lactic-co-glycolic acid) particles), and result in burst release of their drug payload. We hypothesize that these eNPs will, via this unique mechanism, afford a higher intracellular concentration of paclitaxel (Pax), with greater efficacy in the prevention of local recurrence of mesothelioma after surgery that is superior to standard resection or Pax alone without adversely affecting healing at the surgical site. Importantly, we have data demonstrating that eNPs are readily internalized by cancer cells, act as a drug depot, and are superior to the standard Pax-Cremaphor formulation in preventing microscopic malignant disease in vivo.
Mark Grinstaff, NIH
Dissolvable Hydrogel Dressing for the Treatment of Burns
This will study the synthesis, characterization, and evaluation of a hydrogel dressing that dissolves and can be easily removed from the wound surface of a patient with second degree burns with no further trauma. Burns are one of the most common and devastating forms of trauma. Each year, more than 300,000 people die from fire-related burn injuries and millions suffer from burn-related disabilities and disfigurements with psychological, social, and economic effects on both the survivors and their families. Dressing removal is reported to be the time of most pain (after the burn itself) and opioids continue to be the mainstay of treatment for the burn patient. The duration of a burn dressing change in a typical injury requiring ICU/OR level care is often at least 60 minutes with induction of general anesthesia, which can extend to more than three hours depending on the case. At present, all clinically approved available dressings adhere to the wound surface so that each change of dressing leads to traumatization of newly formed tissues on the outer layer of the body’s surface, delayed healing, and great personal suffering for the injured patient. The proposal describes a thiol terminated dendron and a bifunctional NHS-activated PEG that react with each other to form a thiolester linked hydrogel dressing that can be subsequently dissolved by exposure of an aqueous thiol solution via a thiol-thiolester exchange mechanism. These experiments will test the hypothesis that a hydrogel-based, dissolvable burn dressing will provide a barrier to infection, promote wound healing, and be easily removable on demand. Importantly, it presents preliminary data demonstrating the synthesis, characterization, and performance of a dissolvable hydrogel dressing prototype.
Tuning directionality for CO2 reduction in the oxo-acid:ferredoxin superfamily
Exploiting catalytic chemistry for bioenergy production requires a detailed understanding of the molecular mechanisms of multi-electron redox processes, particularly those that transform/capture CO2. Understanding the molecular details of these complex reactions is a major challenge in modern energy science, particularly in the context of CO2 transformations, and the way in which bacteria and archaea capture CO2 for biomass. Here, we have focused on the remarkable catalysts used by nature to achieve either the oxidative liberation of CO2, or its formal reduction (and capture) in the form of useful intermediaries en route to biomass.
The enzymes that achieve CO2 reductions are highly powerful catalysts; yet very little is known about how they work, nor how they can be tuned to favor CO2 reduction chemistry. Through the completion of the project, this knowledge gap will be addressed in the context of the enzymatic chemistry of the oxo-acid:ferredoxin oxidoreductase (OFOR) superfamily, which is capable of CO2 reduction. We believe that our studies of the OFOR superfamily will reveal the molecular details of how nature biases the reactivity of an enzyme to preferentially reduce CO2. These efforts will yield foundational knowledge that will be broadly applicable to marrying the thermodynamics of redox reactions to atomistic information of enzymatic mechanism. We will examine a series of OFOR enzymes through three Aims over a 3-year period.
Their research provides strong evidence that Flavin Adenine Dinucleotide (FAD) plays a structural role in the formation of tetrameric AidB. While their studies clearly show FAD-dependent oligomerization of AidB, they do not address whether FAD also has a catalytic function. However, the picture of AidB that is emerging invokes a role for the DNA-binding domain in localization of AidB to specific genes, while the protective function appears to reside elsewhere on the protein.
In future work, the collaborators will investigate whether this protective function resides with FAD or whether FAD was retained in the evolutionary process solely for its ability to stabilize the AidB tetramer.
This work was supported by National Institutes of Health Grants R01-GM072663 (to Sean Elliott) and P30-ES002109 (to Catherine Drennan) and National Science Foundation Grant MCB-0543833 (Drennan). Professor Drennan is a Howard Hughes Medical Institute Investigator.
The paper is available at http://pubs.acs.org/doi/full/10.1021/bi201340t, or click on the image below.
Disulfide bonds play critical catalytic, structural and signaling roles throughout nature. However, little is known about what governs their reactivity at the molecular level. To gain insights into disulfide bonds, the National Science Foundation, has funded Professor Sean Elliott and his Research Group to use direct electrochemistry to characterize the influence of protein sequence and structure on the redox properties and reactivity of the thioredoxin superfamily.
The 4-year award, which is valued at nearly $700K will provide a new detailed understanding of how thioredoxins are used in Nature to maintain redox homeostasis. The broader impacts of this work will touch deeply on the interface of chemistry and biology. Whether in plant biochemistry, bioenergy sciences or microbial physiology – thioredoxins will provide insights on how disulfide bonds are used to achieve chemical change in life.
Illuminating this process in a fundamental way will translate into new appreciation of fundamental biology. At the same time, the research will advance the training of at all levels (undergraduates, graduate students, post-doctoral faculty fellows) to think quantitatively and chemically in the field of redox biochemistry.
Professor Sean Elliott has received a second Scialog Award from the Research Corporation for Science Advancement. This very competitive award recognizes the highly innovative nature of his work and its potential to be transformative in solar energy conversion.
The project, “High Spatial Resolution Electrochemistry of Biological Inspired Systems,” is a collaboration between Professor Elliott and two other Scialog Awardees, Professor Stefan Lutz, Emory University, and Professor David Cliffell, Vanderbilt University.
Their goal is to address key bottlenecks in the development of biologically inspired systems for solar to fuel production.
This multi-year program is designed to accelerate the work of 21st-century science by funding early career scientists (either individuals or multi-disciplinary teams) to pursue transformative research, in dialog with their fellow grantees, on crucial issues of scientific inquiry. The initial initiative focuses on solar energy because of the economic and national security implications associated with a reliable, domestic, and renewable energy supply. The initial grants also are aimed at supporting research with the potential for rapid translational application and development by the private sector, in the hope that federal and private funding will follow suit.
The project is entitled Transforming heme proteins into solar-driven redox catalysts by site-directed zinc porphyrin mutation and proposes a biological solar-capture strategy, exploiting the multiheme cytochromes of Shewanella oneidensis (So), particularly the quinol-oxidase CymA. The aim is to introduce photo-activatable groups (zinc porphyrins) into the cytochromes of interest thereby actually turning on the microbial charge transport pathways with light.
The research is highlighted in BU Today’s article, “Turning Blood into a Hydrogen Factory: Sean Elliott’s radical research wins RSC grant”
The Department of Chemistry prides itself on faculty who attain an admirable balance between their research and scholarship and their commitment to teaching and advising. Two of our faculty, Professor Sean Elliott and Professor John Caradonna, both renowned researchers, were singularly honored by the College of Arts and Sciences with undergraduate advising and teaching awards.
Sean Elliott received a 2008 Templeton Prize for Excellence in Student Advising. Student recommendations for Professor Elliott were notable for their length and enthusiasm, commenting on how he inspires students and “adds a personal touch to every appointment with his jokes and his clear and present attentiveness.” Prof. Elliott is one of the inaugural recipients of this award, which was endowed by John and Josephine Templeton as a measure of their appreciation for the dedication of members of the Boston University faculty in advising, teaching, and nurturing undergraduates.
John Caradonna received the College of Arts and Sciences’ highest teaching award in 2008, the Gitner Award for Distinguished Teaching. The department’s exit interviews with the graduating majors of the class of 2008 listed him as among the top two professors in the department, and the majority picked his inorganic chemistry course as the very best experience of their undergraduate careers. The Gitner Award for Distinguished Teaching is given every year on Class Day to faculty members whose classroom leadership and student mentoring have been judged outstanding by their departments and by the Dean of the College of Arts and Sciences. The basis of the awards is excellent and distinguished teaching in the broadest sense, including classroom performance, course and curriculum development, advising, and enhancement of the scholarship of teaching and learning.
Sean Elliott receives 5-year Early Faculty Development (CAREER) Award from the National Science FoundationFrom BU Today:
The National Science Foundation honored CAS assistant professor of chemistry Sean Elliott for his research on biological electron transfer, with the Faculty Early Career Development (CAREER) Award, a five year grant that will give Elliott the opportunity to further develop a course curriculum that highlights the intersection of chemistry and biology.
CAREER awards are presented by the NSF to teacher-scholars who are “most likely to become the academic leaders of the 21st century,” according to a release. “Awardees are selected on the basis of creative plans that effectively integrate research and education within the context o fthe mission of their organization.”
Elliott’s work in biological electron transfer examines how organisms convert chemicals into useful energy. The grant will also support Elliott’s study about series of cytochromes, iron-containing proteins. “This is very exciting news,” says Elliott, who joined Boston University faculty in 2002. Elliott majored in Chemistry and English at Amherst College, and completed his Ph.D. in chemistry at Caltech in 2000. He has also done post-doctoral work at the University of Oxford. “In particular, I’m most proud as it reflects the success of my graduate and undergraduate students in the lab as well as in the classroom.”
Professor Sean J. Elliott (Inorganic Chemistry) joined our faculty in Fall 2002. Sean received his B.A. summa cum laude from Amherst College in 1994 in Chemistry and English. He received his Ph.D. with Sunney Chan at Caltech 2000, for his work on the enzymology and biophysical characterization of the copper centers of particulate methane monooxygenase.
Sean comes to us most recents from his postdoctoral studies at the University of Oxford, where he worked with Professor Fraser Armstrong in the Inorganic Chemistry Laboratory (2000-2002). There he used the technique of protein film voltammetry to probe the electron transfer mechanisms of respiratory and oxidoreductase enzymes. We are very pleased to have Dr. Elliott as the newest member of the Chemistry Department.