Reinhard Research Provides Insights into HIV-1
Professor Bjoern Reinhard
Recently reported in PNAS, Bjoern Reinhard and his collaborator at the BU Medical School, Dr. Suryaram Gummuluru, have confirmed a unique HIV-1 DC attachment mechanism using lipoparticles with defined surface composition. The mechanism is dependent on a host-cell–derived ligand, GM3, and is a unique example of pathogen mimicry of host-cell recognition pathways that drive virus capture and dissemination in vivo. These insights provide the basis for the development of artificial virus nanoparticles with host-derived surface groups that inhibit the HIV-1 trans-dissemination pathway through dendritic cells. The virus parasite uses these dendritic cells to facilitate its dissemination, while avoiding recognition.
Gangliosides with α2–3 NeuNAc linkages are important for HIV-1 capture by mDCs. (A) Gag-eGFP VLPs were mock treated or treated with 0.5 units/μL α2–3, 2–6, 2–8 NA. (B) Gag-eGFP VLPs were derived from siRNA-treated HEK293T cells. NT, nontargeting; UGT8, galactosyl transferase; CERT, ceramide transfer protein; UGCG, glucosyltransferases, ST3, GM3 transferase. Capture of VLPs by mDCs was analyzed by FACS (A and B). Data are reported as percentage of eGFP+ mDCs normalized to NT-treated VLPs. (C and D) Ganglioside-deficient HIVLai was derived from HEK293T cells knocked down for NT, UGCG, or ST3. (C) Virions were labeled for p24gag (green) and GM3 (red). Representative fields are shown and the average mean fluorescent intensity (MFI) of GM3 normalized to p24gag ± SD is reported, *P < 0.001, one-way ANOVA with Dunnett’s multiple comparison. (D) Fold decrease of ganglioside-depleted HIVLai capture relative to NT-treated viruses by mDCs is reported. (E) Fold decrease in HIVLaiΔEnv virus capture treated with 0.5 units/μL α2–3, 2–6, 2–8 NA or α2–3-specific NA relative to mock-treated viruses by mDCs is reported. All capture assays represent averaged data from a minimum of three donors, ±SEM, one-sample t test, *P < 0.05, **P < 0.01, ***P < 0.001.
BU Chemistry Day 2012
BU Chemistry hosted more than 100 students from the Boston Community Leadership Academy (BCLA) and English High School on May 4, 2012 for the fourth annual Chemistry Day. The morning long program began with a demonstration session given by BU Chemistry undergraduates and coordinated by Postdoctoral Faculty Fellow (PFF), Dr. Seann Mulcahy. The demonstration explored pH, having fun with liquid nitrogen, synthesizing nylon, and making “Elephant’s Toothpaste.” After the demonstration, students spent time in our undergraduate teaching labs performing experiments in electrochemistry of metals (a variation on a CH 101 undergraduate lab experiment), electrolysis of salt water, and identifying antioxidants using glow sticks. These experiments were coordinated by PFF, Dr. Katie Frato, with assistance by BUWIC (Boston University Women in Chemistry) president Sarah Soltau and undergraduates. Students also attended tours of state-of-the-art chemistry research labs, seeing major instrumentation such as NMR spectrometers and GC/MS instruments and testing a glove box. During these tours, graduate student and postdoctoral researchers also described their work and what it was like to work in a research lab. The morning was capped off with a BBQ sponsored by the department. Photos from the event can be seen at the BU Chemistry Flickr site.
BU Chemistry Day is the culmination of a semester long outreach program created by BUWIC and coordinated by Liz Hirst (BUWIC Outreach Coordinator). During the semester, 2-3 BU students visited classrooms at BCLA, English High School, and Brighton High School every other week to mentor students, assist teachers with instruction, perform demonstrations, and coordinate hands-on experiments.
BU Chemistry is grateful to all of those involved, with special thanks to:
Outreach co-directors: Seann Mulcahy and Katie Frato
BUWIC: Sarah Soltau (President) and Liz Hirst (Outreach Coordinator)
Teaching lab coordinator: Boris Bezverkhny
Undergraduate “Outreachers”: Kyle Kahveci, Will Lyon (English High); Shama Patel, Nicole Buechler, Holly Johnson, Pragya Kalla, James Priestley, Christopher Neil, Zach Bogart (BCLA); and Nick Russo, Josh Nelson, Doug Allison (Brighton High)
Reinhard Article Among Ten Most Read in February
Professor Bjoern Reinhard
The article by Bjoern Reinhard, “Molding the flow of light on the nanoscale: from vortex nanogears to phase-operated plasmonic machinery” (Nanoscale, 2012, 4, 76-90; DOI: 10.1039/C1NR11406A), was amongst the top ten accessed articles from the online version of Nanoscale in February 2012. Launched in 2009, Nanoscale is a new peer reviewed journal publishing experimental and theoretical work across the breadth of nanoscience and nanotechnology.
The Reinhard Group research focuses on new optical materials and their application to interrogate fundamental life processes. They explore the interface between nanotechnology and biological systems. For an overview of current research projects, please visit their group’s website.
Plasmonic nanolens as an internal vortex nanogear transmission. (a) Schematic of the self-similar Ag nanolens proposed in ref 72 (r1 = 45 nm, r2 = 15 nm, r3 = 5 nm, d1 = 9 nm, d2 = 3 nm, ambient index n = 1.0). (b and c) Electric field intensity distribution in the nanolens illuminated on- (b) and off-resonance (c) with the near-field intensity maximum of the nanolens. Far-field (d) and near-field intensity enhancement (e) spectra of the nanolens. (f) The amplitude of the Poynting vector and the phase of the Poynting vector in the x–z plane at the center of the nanolens narrower interparticle gap as a function of wavelength. (g and h) Poynting vector intensity distribution and powerflow around the nanolens off (g) and on (h) the peak intensity wavelength. (i) Schematic of the VNT generated in the nanolens at the peak intensity resonance. Light flux in each nanogear is looped through nanoparticles .
Collaborative Research Discovers New Approach in the Treatment of Liver Cancer
Professor Scott Schaus
Until now, there has been no effective, systemic treatment for liver cancer (hepatocellular carcinoma), the fifth most common cancer worldwide. Writing in the Proceedings of the National Academy of Science (PNAS), Professor Scott Schaus (Chemistry) and Professor Ulla Hansen (Biology and Molecular Biology, Cell Biology & Biochemistry) have reported their discovery of a new protein target for chemotherapy in the treatment of liver cancer — the transcription factor LSF. LSF occurs at high levels in the tumor tissue of patients with liver cancer and is known to promote the development of cancer (oncogenesis) in studies using laboratory rodents.
The co-investigators have identified small molecules that effectively inhibit LSF cellular activity, which in turn slows the growth of the cancer. In particular, they found that one such molecule, Factor Quinolinone Inhibitor 1 (FQI1), derived from a lead compound, inhibits the ability of LSF to bind DNA both in extracts (in vitro, as determined by electrophoretic mobility shift assays) and in cells. Consistent with inhibiting LSF activity, FQI1 also eliminates the ability of LSF to turn up transcription. While FQI1 quickly causes cell death in LSF-overexpressing cells, including liver cancer cells, healthy cells are unaffected by the treatment. This phenomenon has been called oncogene addiction, where tumor cells are “addicted” to the activity of an oncogenic factor for their survival, but normal cells can do without it. This characteristic is very encouraging for use
of such compounds clinically.
Structures of LSF inhibitors
Following in vitro trials, the researchers tested the efficacy of FQI1 in inhibiting liver cancer tumor growth by injecting HCC cell lines into rodent models. FQI1 was observed to significantly inhibit tumor growth with no observable side effects (general tissue cytotoxicity). These dramatic findings support the further development of LSF inhibitors as a promising new chemotherapy treatment for liver cancer.
This work is featured as part of the series, “BU Takes on Cancer,” in BU Today (April 11, 2012).
Citation: T.J. Grant, J. A. Bishop, L.M. Christadore, G. Barot, H.G. Chin, S. Woodson, J. Kavouris, A. Siddiq, R. Gedler, X-N. Shen, J. Sherman, T. Meehan, K. Fitzgerald, S. Pradhan, L.A. Briggs, W.H. Andrews, D. Sarkar, S.E. Schaus, and U. Hansen, “Antiproliferative small-molecule inhibitors of transcription factor LSF reveal oncogene addiction to LSF in hepatocellular carcinoma,” Proc. Natl. Acad. Sci. U.S.A., March 20, 2012, Vol. 109, No. 12, 4503-4508.
Karen Allen Advises on Publishing Ethics for Research
Professor Karen Allen, an Associate Editor of Biochemistry, has contributed to the fifth episode of the American Chemical Society’s series, ‘Publishing Your Research 101.” The episode addresses “Ethical Considerations for Authors and Reviewers.” This series interviews experts such as Professor Allen to obtain their insights on practical, real world questions and issues facing authors of research papers. Further information about this episode and the entire series can be found on the ACS Website.
Renovation Inspires Technology Innovation in Undergrad Organic Lab
BU Chemistry has dramatically improved the undergraduate organic chemistry laboratory by giving students access to major research instrumentation and state-of-the-art technology. By enabling more modern experimentation, these resources foster critical thinking and problem solving skills that prepare undergraduates for graduate and pre-professional schools or for careers in industry. Advanced experimentation also enables more sophisticated student-designed research-type projects.
Renovations and instrumentation
Renovations in the Metcalf Center for Science and Engineering (Summer 2011) have transformed our organic chemistry instructional laboratories into an 6,350 sq. ft. suite with fume hoods and bench areas for each student, auxiliary support space, and a chemical stockroom. Space has been dedicated for an undergraduate instrumentation center for with fully automated high field nuclear magnetic resonance (NMR), ultra-performance liquid chromatography–mass spectrometry (UPLC-MS), Fourier transform infrared spectroscopy (FT-IR), and gas chromatography-mass spectrometry (GC-MS). Microwave reactors allow for rapid reaction rates, enabling multistep syntheses to be undertaken in a single day.
Advanced Technology in the Laboratory Curriculum
The entire laboratory curriculum of our sophomore-level organic chemistry sequence has been transformed with the adoption of the “paperless laboratory” through the use of electronic laboratory notebooks. Spearheaded by Professor John Snyder and Professor Scott Schaus and Postdoctoral Faculty Fellow, Seann Mulcahy, integration of these technology resources have enabled the creation of an open-access repository of laboratory protocols, design of laboratory experiments that facilitate sharing of data between students and between disciplines, exposure to automated NMR, GC-MS, and UPLC-MS, and remote download and manipulation of spectroscopic data.
Fast Forward to the 21st Century -The new instrumentation advances undergraduate capabilities well beyond those in traditional sophomore organic textbooks that repeat traditional experiments. Instead, we have designed novel, research-oriented, exploratory experiments that have applicability to modern organic chemistry. These include cross-coupling experiments, olefin metathesis, and many others. Experiment protocols are available on BU’s Digital Common site (DCommon), an open-access online repository that is accessible not only by our students, but by outside instructors as well. Users can be granted upload privileges to deposit modified or new protocols thereby creating a rich resource to the worldwide research community. In addition, a DCommon collection of NMR and UPLC-MS spectra is being compiled as a teaching tool for organic chemistry courses.
- Major Instrumentation – BU is unique in using the latest instrumentation for routine, hands-on training at the sophomore level. The laboratory’s state-of-the-art instrumentation also allows comprehensive characterization of synthetic material prepared in each experiment. Students now routinely run 1H and 13C NMR (and 2D COSY), UPLC/MS, GC/MS, and FT-IR on their own samples and to obtain a set of data which approaches the quality needed for publication.
- Into the Cloud – Our students are now using fully electronic laboratory notebooks, which they populate on their laptops with reaction details, procedural notes, and safety protocols. Analytic data and spectra (manipulated and interpreted remotely) are uploaded into the notebook and serve as part of their final laboratory reports.
High School Researcher in Schaus Lab Wins SIEMENS Award
Joshua Kubiak
The Research Internship in Science & Engineering Program (RISE) provides academically motivated high school seniors the opportunity to conduct university-level research in state-of-the-art laboratories.
In the summer of 2011, Joshua Kubiak, a senior from the Louisiana School for Math, Science and the Arts (Natchitoches, LA), joined the laboratory of Professor Scott Schaus to conduct research for 3 months on Asymmetric Conjugate Addition of Ortho-Quinone Methides as a Pathway to Communesin Analogs.
Professor Scott Schaus
Under the mentorship of Professor Schaus and graduate student, Yi Luan, Joshua made a molecular scaffold which can then be built upon to create chemical compounds with potential medicinal applications. The quality of his research has been recognized by a Siemens Foundation Award.
Joshua is the first student from his school to be named a Regional Finalist in the Siemens Competition, and he plans to pursue a career in drug design and development.
NIH Funds Porco Group to Synthesize Bioactive Natural Products
Professor John Porco
The Porco Research Group has received a 4-year, $1.2 million award from the National Institutes of Health for their proposal, Chemical Synthesis of Bioactive Flavonoid and Xanthone-Derived Natural Products.
Undertaken in conjunction with biological collaborators, including Professor Tom Gilmore (BU Biology) and Dr. John Beutler of the National Cancer Institute’s Center for Cancer Research, the goal of the research is to develop new chemical methodologies to enable the synthesis of bioactive flavonoid and xanthone-derived natural products that could lead to biologically active antitumor and anti-infective agents. Specifically, such agents will be useful as novel pharmacological therapies and as cytotoxic agents against both human cancers and malaria.
Their aims include total syntheses of anticancer agents such as the kuwanons and related prenylflavonoid Diels-Alder natural products as well as the bioactive tetrahydroxanthones blennolides A and B.
The award enables an exciting new research direction for Professor Porco and his collaborators involving the use of nanoparticles in organic reactions, asymmetric catalysis, and novel cycloaddition strategies.
Jasti Group Research on Nanohoops Featured on ACS Website
Professor Ramesh Jasti
In its Noteworthy Chemistry page, the American Chemical Society website has highlighted the work of Professor Ramesh Jasti and his Research Group on the blue shift of Cyclo-p-phenylene emissions as a nanohoop size increases.
The emission color of an inorganic semiconductor quantum dot shifts bathochromically with increasing particle size. Similarly, the luminescence color of a linear p-phenylene (LPP) oligomer red-shifts with increasing chain length. [n]Cyclo-p-phenylenes (CPPs) are cyclic forms of LPPs, or “nanohoops”.
Cyclo-p-phenylene emissions blue-shift as ring size increases
The aim of their work is to determine how the emission color of CPPs change with ring size.
Reinhard Cell Signaling Research Featured in European Innovation Journal
Dr Bjoern Reinhard Media.EU Interview
Research Media.EU disseminates information about advances in innovation to the wider scientific, technology, and research communities. Among its focus areas is Nanotechnology and US Research.
Recently, they interviewed Professor Bjoern Reinhard about his work on Epidermal Growth Factor Receptors (EGFRs), which are important cancer biomarkers, and which Research Media has identified as an important innovation in nanotechnology.
In addition to obtaining Professor Reinhard’s insights, the article described in detail the impact of this work and profiled the Reinhard Laboratory. To download a PDF of the interview/profile, click here.
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