Category: Grants & Funding
Professor Mark Grinstaff is a recipient of one of the first Boston University MSE Innovation Grants for his research proposal Real-time control of drug release from superhydrophobic biomaterials using clinical ultrasound.
These awards from Boston University’s College of Engineering, Division of Materials Science & Engineering aim to encourage innovation and risk taking.
The Burroughs Wellcome Fund (BWF) uses Collaborative Research Travel Grants to facilitate biomedical research among laboratories in the US and abroad. This February, two Chemistry groups received these competitive awards.
One of the grants will support Professor Pinghua Liu and his graduate student, Jinzhao Shen, to go to Beijing to work in the laboratory of Professor Xiaoping Chen of the Chinese Academy of Sciences. They will collaborate with Professor Chen’s group to develop new anti-microbial drugs, focusing initially on new anti-malaria drugs for multi-drug resistant strains. Specifically, they will build marine natural product libraries and screen them for anti-malaria activities.
The second grant will support graduate student, Daniel Saltzberg, in the Allen Group. Mr. Saltzberg will work with Dr. Hiro Tsuruta’s group at the Stanford Synchrotron Radiation Lightsource to probe the specific interactions governing ligand binding in a large superfamily of metabolic enzymes. These studies will provide insight into the evolution of functional diversity in this superfamily.
There are many medically important drug targets that current drug discovery technology is not able to address. Collaborative basic research in Chemistry, Biology, and Biochemistry is key to solving these intractable problems to enable the discovery of new classes of drugs. A multidisciplinary team at Boston University, led by Associate Professor of Chemistry Adrian Whitty, aims to develop new approaches for challenging molecular targets. The National Institute of General Medical Sciences awarded this team a 4-year, $1.6 million grant entitled Design of Macrocyclic Inhibitors of the NEMO/IKKα/β Protein-Protein Interaction.
Only about 10% of the potential drug targets in the human genome have been successfully targeted with marketed drugs. Of the remaining 90%, many are intracellular proteins whose function is critically dependent on their reversible interactions with other proteins. Despite decades of effort by the pharmaceutical industry, developing oral drugs that inhibit protein-protein interactions (PPIs) has rarely succeeded and has become recognized as a major scientific and technological challenge.
The primary goal of this project is to determine whether the use of a class of natural product-inspired compounds called macrocycles constitutes a broadly applicable method for developing oral drugs against PPI targets. As a first challenge, the team is attempting to develop macrocycles that block the activity of NEMO, a key component of the IKK complex that activates NF-κB signaling. Chronic hyperactivity of the NF-κB pathway is associated with many human inflammatory diseases and cancers. Thus, the development of drug-like inhibitors of this pathway is highly relevant to public health.
The work will determine whether appropriately designed synthetic macrocycles can inhibit PPI targets while maintaining good drug-like properties. In terms of NF-κB and disease, their work will provide a means for testing whether inhibiting the interaction of NEMO with IKK—as a more targeted alternative to completely ablating all IKK activity—represents a useful new approach for attenuating inflammation.
In addition to Professor Whitty (quantitative biochemistry and drug discovery), the multidisciplinary research team comprises Professors Sandor Vajda and Dima Kozakov (computational chemistry), John Porco and Aaron Beeler (macrocycle synthesis), Karen Allen (X-ray crystallography), and Tom Gilmore (NF-κB pathway biology).
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 National Science Foundation Faculty Early CAREER awards are presented to teacher-scholars who are “most likely to become the academic leaders of the 21st century.” The Department is proud to announce that this year, Professor Björn Reinhard has received this important award for his proposed research on “Frequency Domain Plasmon Fluctuation Spectroscopy For Single Biopolymer Mechanical Sensing.”
In this work, he plans to develop novel plasmon fluctuation spectroscopy with which to characterize the mechanical properties of individual biopolymers with unlimited observation time. By transitioning from a time to a frequency domain analysis, his plasmon fluctuation spectroscopy will provide insight into the structural properties of short DNAs, RNAs, and their protein complexes on the single molecule level. This research is part of his Nano-Bio Interface Lab, which aims to design, implement, and characterize new tools for imaging and manipulation of “hard” (inorganic) and “soft” (biological) materials with the ultimate goal of generating reliable tools that can provide insights into fundamental biological processes on a single molecule level.
In addition, Prof. Reinhard’s project will offer high school, undergraduate, and graduate students the opportunity to participate in an exciting collaborative research and education program. Dr. Reinhard plans to invite undergraduates and interested high school students who have completed his NanoCamp to obtain hands-on research experience in the interdisciplinary research effort.
Adrian Whitty and group receive NIH Award to perform quantitative analysis of RET Receptor activation and signaling
The Whitty Group has received a 5-year, $2 million award from the NIH. Growth factors (GFs) are messenger proteins that mediate the signals between cells that regulate critical functions such as cell growth, maturation, and death. In comparison with other medicinally important protein classes (enzymes, ion channels and G protein-coupled receptors) little is known about how GF receptors perform their function. This project aims to address this important knowledge gap by using the GF receptor RET, which is important in sustaining the survival of a key population of nerve cells in the spinal cord, as a model system to elucidate how GF/GF receptor interactions are coupled to intracellular signaling and to the resulting cellular response. If successful, the new knowledge and experimental methods it will deliver will contribute to innovative and improved approaches to discovering and developing drugs that target GFs and their receptors.
NIH funds Pinghua Liu and his group to perform mechanistic studies of enzymes in isoprenoid biosynthesis
The goal of this award ($1.9 million over 5 years – 2010-2015) is to characterize the mechanism of a key enzyme in the deoyxylulose biosynthetic pathway as well as identify its key partner proteins. This pathway, identified only in bacteria and plants, produces the required compounds for isoprenoid synthesis. The results of this work could eventually lead to new broad-spectrum antibiotics or toward more efficient bioengineering based isoprenoid production. The work has developed an enzyme preparation that is many times more active than those previously reported, providing a crucial piece to illuminating enzymes. These isoprenoid biosynthetic studies will guide the development of mechanism- based inhibitors of the DXP pathway enzymes, which can be used as broad-spectrum antibiotics. The public health benefit will result from the development of effective new treatments for drug-resistant strains of pathogens (e.g., tuberculosis), currently of increasing concern worldwide.
Professor Karen Allen is leading the HAD Bridge Project of the NIH U54 award to the University of Illinois entitled “Collaborative Center for an Enzyme Function Initiative,” ($25 million over 4 years, John Gerlt, PI). Known as “GLUE Grants,” these prestigious awards provide resources to currently funded scientists to form research teams to tackle complex biomedical problems that are beyond the means of any one research group. This consortium will facilitate the discovery of in vitro enzymatic and in vivo metabolic/physiological functions of unknown enzymes discovered in genome projects. The consortium is organized around five Bridging Projects and seven Cores. Professor Allen and her collaborator, Professor Debra Dunaway-Mariano, University of New Mexico, were invited to lead the HAD Bridge Project based on their 15 years of investigations on the chemical and catalytic mechanisms of the phosphotransferases in the haloalkanoic acid dehalogenase (HAD) superfamily of proteins (“Mechanism and Function in HAD Phosphotransferases,” NIH R01 GM061099. Their work has successfully uncovered and confirmed the structural determinants of substrate specificity in all three subfamilies of the superfamily and are using this knowledge to predict the substrates for enzymes of unknown function, identifying the associated metabolic pathways of at least six members from various bacterial species. The HAD efforts will be greatly extended, enhanced, and enabled by the other Cores and Bridging Projects of the consortium, including the Protein Core, the EN and AH Bridges, Sequence/Genome Analysis Core, Microbiology Core, Computation Core, and the Structure Core. In turn, the HAD Bridge Project, will afford comprehensive kinetic and mechanistic expertise to provide test cases for and utilize the facilities and expertise of the Cores.
Professor John Porco and his group have received a 4-year, $1.6 million award (2010 to 2014) to develop and refine biomimetic syntheses using copper-mediated enantioselective oxidation processes; photochemical cycloaddition employing excited state intramolecular proton transfer (ESIPT); and asymmetric reactions of acylphloroglucinols. Professor Porco and colleagues are applying these methodologies to synthesize complex natural products, including bisorbicillinol, sorbicillactone A, aglaiastatin, ponapensin, and myrtucommulones A and B. Collaborating with the Porco Group is Prof. Linda Doerrer who is performing mechanistic investigations to understand copper-mediated enantioselective oxygenase and oxidase processes and also develops catalytic, asymmetric oxidation processes. Likewise, a continuing collaboration with Professor Eric N. Jacobsen and coworkers (Harvard University) seeks to identify chiral thiourea photocatalysts for asymmetric photocycloadditions. More
Professor Tom Tullius has received a 2009 Senior Scholar Award in Aging” from the nonprofit Ellison Medical Foundation. The Foundation supports basic biomedical research on aging relevant to understanding lifespan development processes and age-related diseases and disabilities. The Ellison award supports a new project in the Tullius lab on genome damage and aging, particularly the development of whole-genome maps of oxidative DNA lesions at single-nucleotide resolution. Genome damage caused by reactive oxygen species has long been thought to be associated with aging and neurodegeneration. Using next-generation DNA sequencing methods and bioinformatic tools, the Tullius group will relate the damage map to the underlying genes and functional regions of the genome. The research will obtain unique new information on how oxidative damage affects the genome and thereby contributes to aging.