Prof. Pinghua Liu and his Group pursue highly interdisciplinary research involving organic synthesis, molecular biology, bioinformatics, and enzymology. This combined expertise will be used to conduct their 3-year National Science Foundation Funded project, “Mechanistic Studies of New C-S Bond Formation Chemistries.”
Ergothioneine is a unique thiol-imidazole-containing natural amino acid isolated nearly a century ago. Due to its unusual redox properties, it plays many beneficial roles in human health (e.g., conserving/maintaining antioxidant levels). It can be used as one of the key components in many commercial products, including dietary supplements, personal care products (skin care and cosmetics), and veterinary products. The Liu Group investigations will allow them to fully establish ergothioneine in an in vitro catalytic system and differentiate among several proposed mechanistic models. These studies will guide the future production of ergothioneine using a synthetic biology approach.
In addition to the science, this research program will provide an interdisciplinary environment in which to train undergraduate, graduate, and high school students in how to investigate major problems at the interface of Chemistry and Biology.
The Department of Chemistry is very pleased to announce that Prof. Ksenia Bravaya, a theoretical chemist, has joined our faculty. She comes to Boston University from her postdoctoral position at the University of Southern California (2009-2013), where she did research with Prof. Anna Krylov. Prof. Bravaya received her Ph.D. in Theoretical and Computational Quantum Chemistry from the Lomonosov Moscow State University (2008). She has received the ACS Physical Chemistry Division Postdoctoral Research Award (2011), the Burg Postdoctoral Teaching Award, University of Southern California (2010), and the WISE Merit Award for Excellence in Postdoctoral Research, University of Southern Calfornia (2010).
Prof. Bravaya’s research aims to develop new theoretical methods targeting processes involving multiple electronic states, chemistry of open-shell species in magnetic fields, and metastable systems. She will apply this new computational tool kit, as well as existing state-of-the-art quantum chemistry approaches to the investigation of the mechanism of magnetoreception in avian birds, tuning the optical properties of fluorescent proteins, studying processes involving metastable electronic states, and exploring the electronic structure of new magnetic materials. Her goal is to develop a theoretical chemistry framework for studying complex photoinduced processes and spin effects in biomolecules and novel materials (e.g., molecular electronics / spintronics, magnetophotovoltaics, and biophotonics).
For a second year in a row, Prof. Ramesh Jasti‘s group has hosted students from the Steppingstone Foundation to share with them the excitement of nanoscale research. Steppingstone is a non-profit that develops and implements programs which prepare urban schoolchildren for educational opportunities that lead to college success.
This year the students learned about nanoscale materials and how their unique properties are a function of their size. The day started with fun demonstrations of liquid nitrogen and an “explosive” Pringles can. The students then paired off to perform two separate hands-on laboratory experiments. The first lab illustrated the principle of chemical sensing. Using glow sticks, students analyzed a number of molecules to determine their anti-oxidant properties. Strong anti-oxidants would result in decreased fluorescence that visually detectable. This approach to sensing molecules is of strong interest for detection of environmental pollutants, food safety, product testing, water treatment, explosives detection and numerous other applications.
The second lab was designed to teach the students about the importance of polymers in modern life, particularly as they relate to material applications. The student pairs synthesized their own Nylon strands. To “up the fun factor,” they were challenged to a contest to see who could produce the longest continuous piece. With a prize of candy bars on the line, the students took the challenge seriously.
The day wrapped up with a casual pizza lunch, with the visitors asking lots of questions about not only graduate school, but college life and what being a science major is like. The graduate students had as much fun as the high school visitors, and look forward to the continued partnership of the Steppingstone Foundation and the Jasti Group.
A new study co-authored by John A. Porco, Jr., Professor of Chemistryand Diector of the Center for Chemical Methodology and Library Development at Boston University (CMLD-BU), along with collaborators at the Whitehead Institute has identified rocaglamide A, an inhibitor of translation initiation, as a strong
inhibitor of Heat Shock Factor 1 (HSF1) activation. HSF1 inhibitors have received gained significantattention their potential role in the rapid development of anticancer drugs with completely new modes of action.
The study, published in the journal Science, found that rocaglamide A, a naturally occurring anticancer agent, effectively inhibits HSF1 activation. The article, “Tight Coordination of Protein Translation and HSF1 Activation Supports the Anabolic Malignant State,” S. Santagata et al., Science 341, 1238303 (2013), is available online at http://dx.doi.org/10.1126/science.1238303).
The study is the latest product of a three-year research grant from the National Institutes of Health awarded to Porco and Dr. Luke Whitesell, senior scientist in the laboratory of Prof.
Susan Lindquist at MIT’s Whitehead Institute. This combined biology/chemistry team came together specifically to identify highly potent and selective HSF -1 inhibitor probes with useful activity in vivo.
The College of Arts and Sciences Press Release can be accessed here.
Collaborators, Dr. Bjoern Reinhard, BU Chemistry, and Dr. Suryaram Gummurulu, BU School of Medicine, Department of Microbiology, have received an award from the NIH to investigate the role and mode of action of non-virus encoded surface functionalities in the capture of HIV-1 by dendritic cells. Entitled ”Elucidating Non-Virus Encoded HIV Capture through Artificial Virus Nanoparticles (AVNs),” the project involves an interdisciplinary approach requiring expertise in virology and nanotechnology.
Dr. Gummuluru will oversee the biological aspects of this project, including the generation and purification of virus-like-nanoparticles, isolation and characterization of primary dendritic cells and other cell sources, and the development of the biological reagents (e.g., antibodies and virus mutations) required for these studies. Dr. Reinhard will oversee the fabrication and characterization of AVNs and will lead the the electron microscopic and optical imaging studies.
Artificial virus nanoparticles with host-derived surface groups that inhibit HIV-1 infection at the portal of entry and that – by design – evade the development of virus-encoded resistance, as well as the clearance through the host’s immune system will pave the way to highly efficient nanoparticle-based therapeutic strategies against HIV-1, a disease that affects 34 million people worldwide.
MIT Whitehead Institute senior scientist, Dr. Luke Whitesell, and Boston University’s Prof. John Porco, Director of the CMLD-BU, have received a 3-year award from the NIH entitled “Inhibiting the Heat Shock Factor 1 (HSF1)-regulated transcriptional program in cancers.” This combined biology/chemistry team aims to identify highly potent and selective HSF-1 inhibitor probes with useful activity in vivo. These inhibitors will serve as promising leads for the rapid development of useful anticancer drugs with a completely new mode of action. Luke Whitesell is a pediatric oncologist whose research in the laboratory of Prof. Susan Lindquist is focused on cellular heat shock response (HSR) and heat shock proteins, a class of molecules that guides other proteins to fold correctly. HSF1 is the master regulator of the HSR maintaining protein homeostasis during times of proteotoxic stress. It functions as a transcription factor, binding to and coordinating the expression of numerous genes, in effect, acting as a “transcriptional program.” This program can vary depending on the particular cell and stress type.
While Dr. Whitesell and his colleagues have shown that HSF1 is co-opted by tumor cells to promote their own survival at the expense of their hosts, they do not know how the HSF1 coordinates during malignancy, how it might relate to a classic HSR, and whether it impacts human cancer. They have turned to the Porco laboratory for its expertise in the synthesis of complex natural products and derivatives, as well as library synthesis and medicinal chemistry. The Lindquist laboratory’s ~300,000 compound high throughput screen for inhibitors of HSF1 identified the natural product, rocaglamide. In this work, John Porco and his group will optimize the HSF1 inhibitory activity of the rocaglate scaffold; optimize the scaffold’s pharmacological properties; and evaluate the antitumor activity of rocagalate analogs in mouse models of cancer.
The Porco laboratory’s unique photocycloaddition methodology developed for the synthesis of various targets is the basis of the medicinal chemistry efforts in the current award to optimize these compounds as HSF-1 inhibitors.
This fall, Chemistry welcomes three new instructors to its teaching core. Dr. Rebecca Loy has joined the department as Course Coordinator for the organic chemistry laboratory program (CH 203/204/214). In addition to developing the laboratory curriculum and giving the pre-laboratory and course lectures, she directs and trains the courses’ Teaching Fellows and Undergraduate Assistants. Prior to coming to Boston University, Dr. Loy was a postdoctoral fellow with Professor Melanie Sanford at the University of Michigan, studying palladium catalyzed perfluoroalkylation of arenes and vanadium redox flow batteries. Dr. Loy’s academic studies began at the University of California, Berkeley where she obtained her bachelor’s degree in 2004. While there, she conducted research under both Professors Robert Bergman and F. Dean Toste. She studied both titanium catalyzed hydroamination reactions of allenes and rhenium catalyzed glycosylation reactions. She obtained her Ph.D. from Harvard University in 2009 under the direction of Professor Eric Jacobsen studying asymmetric intramolecular oxetane openings catalyzed by cobalt salen complexes.
In addition two new Postdoctoral Faculty Fellows (PFFs), Dr. Kristen Mascall and Dr. Lynetta Mier, have joined the PFF Program. The innovative program provides a two-year, full time appointment in the Department of Chemistry for recent Ph.D. graduates who plan to pursue academic careers at 4-year liberal arts colleges. (Since its founding in 2002, there have been 23 PFFs.) In addition to her teaching, Dr. Mascall is conducting research in medicinal chemistry with Professor Aaron Beeler. She received her Ph.D. in Chemistry from Dartmouth College (Hanover, NH) in 2012. Dr. Mier is conducting research in ultrafast spectroscopy with Professor Larry Ziegler. She received her Ph.D. from Ohio State University in 2012.
Gas hydrates – ice with small molecules trapped in cages – are important for the energy sector because they store natural gas and carbon dioxide, block gas pipelines with an enormous cost impact, and hold potential for hydrogen storage and water purification. In a 3-year, $500K award, the Department of Energy has funded Prof. Tom Keyes to uncover the mechanism, or pathway, of gas hydrate formation. The pathway is a complex sequence of steps involving solvation, association, nucleation, growth, and a first-order-like transition, with a free energy barrier and unstable regime of thermodynamic states. Consequently, the theory of hydrate formation is in an early stage, and computer simulations using conventional algorithms have been hampered by the rarity of rate-limiting visits to the barrier.
Continuing their highly productive (32 publications), 20-year collaboration, Professor Karen Allen and Dr. Debra Dunaway-Mariano, University of New Mexico, have received a 4-year, $1.26 million award from the NIH. The team is known for much of the current understanding of catalysis and specificity of the Haloalkanoic Acid Dehalogenase Superfamily (HADSF). This current award, “Structure and Function of HAD Phosphatase Partners Dullard and Lipin,” represents a new and highly innovative research direction for the the Co-Investigators. Using an interdisciplinary approach, they will investigate the structural basis for the function of two enzymes that utilize the same protein scaffold to interact with and dephosphorylate macromolecules and phospholipids at the cell membrane. The Co-Principal Investigators bring their respective expertise to address the problem. Karen Allen will direct the protein chemistry, bioinformatics, X-ray crystallographic and Small-angle X-ray Scattering aspects of this project. Debra Dunaway-Mariano will direct the substrate screening, assay development, and radio-labeled vesicle binding studies.
By defining the structural features of enzymes that allow recognition of specific proteins and cell membrane components, the study will provide significant insight into the complexities of cell lipid metabolism. The findings will lay the foundation for the rational design of therapeutic agents to treat the diseases associated with diabetes and clinically identified defects in fat metabolism.
The National Science Foundation’s Research Experience for Undergraduates Program supports active research participation by undergraduate students in any of the areas of research funded by the National Science Foundation. For the second time, BU Chemistry has received one of these coveted site awards. Focused on the theme “Fundamental Research in Chemistry Addressing Problems in Biology,” the 3-year program (2012-2015) is led by Professors John Snyder (Principal Investigator) and Linda Doerrer (Co-PI).