Inorganic / Bioinorganic Chemistry |
Organic Chemistry |
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Theoretical Chemistry |
Physical Chemistry / Chemical Physics |
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Biological Chemistry / Biology |
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1. Lanthanide Binding Tags - Professor Karen Allen, Chemistry Department - Biological Chemistry - The Allen Laboratory has pioneered and developed the use of Lanthanide binding tags (LBTs), the next generation of fluorescent tags. Since this one tag can potentially aid in protein purification, characterization, structure determination, and imaging, it may provide new, critical tools for proteomics and medical research. LBTs are short polypeptides (15-25 amino acids) derived from calcium-binding motifs and modified to bind trivalent lanthanide ions with nM affinity. The goal is to establish stable complexes with physical properties that are useful in biochemical and biophysical investigations. Because the LBT tags are small, they have minimal impact on the structures and functions of proteins to which they are fused. Furthermore, because they are composed exclusively of amino acids, these tags can be fused to proteins of interest using standard molecular biology techniques. In the past 5 years, the Allen Laboratory has had six undergraduate researchers in their group, including summer researchers, and their contributions have been significant. For example, the work of one student allowed the design, mutation, expression, purification and crystallization of a new tag with enhanced properties for binding of the lanthanide Gd3+ and magnetic resonance imaging (MRI). Preliminary studies suggest that this unique agent has properties similar to commercial contrast agents while being composed entirely of naturally occurring amino acids. The next step forward will be to design and optimize an MRI LBT fused to the cancer-related growth factor VEGF in order to “light up” affected cells. REU students participating in this project will gain experience in the areas of molecular biology as applied to protein engineering, protein purification, and X-ray crystal structure determination. This past summer, a PROSTARS student isolated and crystallized 2-keto-3-deoxynononate-9-phosphate synthase, an important enzyme for helping bacteria avoid the host immune system.
2. Understanding the Chemical Basis of the Genetic Disease Phenylketonuria (PKU) - Professor John Caradonna, Chemistry Department – Inorganic/Bioinorganic Chemistry - The Caradonna Group is investigating the chemistry of phenylalanine hydroxylase (PAH), a non-heme iron pterin-dependent monooxygenase that catalyzes the conversion of phenylalanine to tyrosine. Defects in PAH, which cause classic phenylketonuria (PKU), increase serum phenylalanine concentrations and result in abnormal accumulation of phenylalanine-based metabolic products. These products cause defective myelination of the central nervous system and result in postnatal brain damage and severe mental retardation. PKU is the most common inborn error in amino acid metabolism of clinical importance (1 in 50 individuals carry the disease trait, with an average incidence of 1 in 10,000 for Caucasians). The non-heme iron PAH-active site is of additional interest because it performs the same spectrum of chemical transformations as cytochrome P450 without benefit of a heme prosthetic group. The Group utilizes a variety of enzyme mechanistic, molecular biological, and biophysical techniques to investigate the mechanism of both wild type enzyme and selected mutants that induce PKU in humans. The REU student will be taught how to perform standard gene manipulations to generate missense mutations of PAH that are of clinical interest. The student will then learn how to over-express, purify, and characterize the resulting PKU-inducing enzyme using protein purification methods already developed in the lab for this purpose. Detailed enzyme kinetic studies using optical (UV/vis) spectroscopy and mass (LCMS) spectrometry will enable the description of the mechanism followed by these mutations and aid in the identification of the particular step(s) in the mechanism that the genetic mutation has altered. These observations will then be placed in the context of crystal structures of these mutant enzymes in the presence of substrate and/or cofactor to offer a detailed description of this important genetic disease.
3. Biosynthesis of plant indolic defense compounds and identification of their biological targets - Professor John Celenza, Biology Department – Chemical Biology - REU students will participate in two projects in the Celenza laboratory: 1) One goal is to exploit the power of yeast genetics to learn about which normal cellular mechanisms are targets of plant defense compo
unds. The yeast Saccharomyces cerevisiae is a single-celled eukaryotic organism and it is likely that knowledge gained from studying the biological effects of these compounds in yeast will be applicable to animal cells. We have established growth conditions to screen for yeast mutants with altered sensitivity to several of these compounds including camalexin and indole-3-acetonitrile. The student researcher will screen through a large arrayed collection of yeast mutants to identify strains with more or less sensitivity to these compounds. This collection contains over 5500 yeast strains, with each strain containing a loss-of-function mutation in a different yeast gene. This collection contains mutations in all yeast genes that are not required for viability. Any strain that has an altered response to a given compound can then be traced back to a specific gene and function. 2) A second goal is to understand how plants regulate synthesis of these various compounds from the amino acid tryptophan. Our laboratory has a series of mutants that have reduced tryptophan biosynthesis or altered tryptophan catabolism. Student researchers will learn how to analyze these mutants for production of indolic glucosinolates and camalexin. An REU student helped screen the yeast mutant library for yeast mutants more sensitive to indole-3-acetonitrile. In addition, the student used chemical analogs of tryptophan and its precursors to follow synthesis of indolic glucosinolates and camalexin in various Arabidopsis mutants. The student's research will be included in a paper the Celenza Group plans to submit in 2010.
4. Condensed Phase Excited State Dynamics - Professor David Coker, Chemistry Department - Theoretical Chemistry - When molecules are photoexcited in solution they relax by various means, including loosing energy to their environment or by breaking bonds and reacting. The Coker Group conducts research directed at understanding these processes. In their projects, they use and develop new theoretical and computational methods to explore how electronic and vibrational excitation of reactant molecules in different environments can influence the outcome of chemical reactions of these molecules. Electronic and vibrational relaxation of excited reactants is, in general, fundamentally quantum mechanical in nature so the methods they use must accurately describe the transfer of energy between the classical environment and the quantal reactive system.
5. Double salts [M]+[M]- for use in nanowires - Professor Linda Doerrer, Chemistry Department – Inorganic/Materials Chemistry - The Doerrer Group has been working on the bottom-up synthesis of nanowires for several years. Such nanoscale electronic devices have infinite potential for use in biology in micro- or nanoscale diagnostic instruments. Initial work resulted in a new family of double salts [M]+[M]- which were assembled by electrostatic forces. In several cases, infinite chains of metal-metal interactions resulted from metallophilic interactions among the cations and anions. A former REU participant (summer 2008) worked on a series of Cu/Pt double salts. The Doerrer Group has also begun incorporating light harvesting groups into their studies. During the summer of 2007, a previous REU participant prepared several compounds related to the well-known organic semi-conductor copper phthalocyanine (CuPc) which is currently being written up for publication. Future studies will focus on (i) increased conductance of these nanowires (via changes in the spin-state composition), and (ii) increased capacity for NIR light harvesting to include allow them to be powered externally and non-invasively. Students involved in this work use both air-stable and air-sensitive synthetic techniques, Schlenk lines and dry boxes, and use a variety of spectroscopic methods including multinuclear NMR, GC-MS, ESI-MS, IR, UV-vis-NIR, and EPR spectroscopies. Students also have access to X-ray diffraction and VT magnetic susceptibility measurements through long-standing collaborations. Since coming to BU in 2006, nine undergraduates have performed research in the Doerrer Group and including two REU students (2007, William Barksdale, University of North Texas, and in 2008, William Kochemba, Westminster College).
6. Protein Electrochemistry of Biological Disulfide Bonds -
Professor Sean Elliott, Chemistry Department – Inorganic/Bioinorganic Chemistry - The Elliott Group's research centers on the use and development of protein electrochemistry to ask fundamental questions about how biological systems tune and control the redox chemistry of fast and reversible processes. Projects study the structure-function relationship of biological electron transfer in model systems that include: simple electron transfer proteins (cytochromes c551 and thioredoxins), complex cytochromes that contain as many as ten heme units, and multi-electron redox enzymes containing several redox cofactors. The work encompasses traditional enzymology, molecular biology, surface science and electroanalysis. The Group's efforts have benefited greatly from the contribution of undergraduate researchers, and one such UROP student pioneered its studies of the disulfide bond electrochemistry of the protein thioredoxin (Trx). An REU investigator will continue this work by constructing and examining novel Trx mutant proteins that are proposed to have greatly modulated redox characteristics. The protein sequence of a single loop motif (-CXXC-) is hypothesized to act as a ‘rheostat’ of the thioredoxin midpoint potential. Thus, the REU student will begin her/his project initially collaborating with current group members to design a mutation in this loop that should greatly perturb the potential. In subsequent experiments, the student will generate the site-directed mutant, prepare the pure mutant protein, conduct the electrochemical analysis, and analyze the resulting data.
7. Thiol-reactive inhibitors of the NF-kB signal transduction pathway - Professor Thomas Gilmore, Biology Department – Chemical Biology - The NF-kB signal transduction pathway regulates a variety of key organismal and cellular processes, including various immune responses, certain developmental processes, and cell proliferation and survival. In addition, the NF-kB pathway is misregulated in many human diseases (e.g., inflammatory diseases and cancers). As such, there is great interest in developing chemical probes to understand the proteins involved in this pathway and chemicals that can specifically modulate NF-kB activity. In collaborative studies with Dr. John Porco (Chemistry), the Gilmore Group has been characterizing the anti-NF-kB activity of several natural product-derived compounds. In these studies, they seek to identify the targets for these drugs in the NF-kB pathway and to understand how these compounds affect NF-kB signaling. Several of these compounds target thiol groups in cysteine residues on target proteins. Therefore, in this project, an REU student would use cellular, molecular, and biochemical assays to identify and characterize novel natural product-based inhibitors of the NF-kB pathway. These approaches include tissue culture experiments, Western blotting, DNA-binding assays, site-directed mutagenesis, and in vitro kinase assays. Over the past 5 years, the Gilmore Laboratory has had 26 undergraduates, including summer researchers from outside BU. In 2008, they hosted an ACS IREU student from the Johannes Gutenberg University in Mainz and in 2009, they hosted an ACS IREU student from Ludwig-Maximillian University.
8. Nanoscience and Nanotechnology - Professor Bennett Goldberg,
Physics Department - Chemical Physics -Current research focus includes nanoscale imaging of subcellular processes and interferometric determination of DNA dynamics on surfaces. Near-field imaging of photonic bandgap, ring microcavity and single-mode waveguide devices identifies internal mode structure and informs resonant biosensor fabrication and development of waveguide evanescent bio-imaging techniques. Subsurface solid immersion microscopy for Si inspection and thermal imaging is being extended to high collection efficiency for quantum information processing in single quantum dots. Room and low-temperature resonant Raman scattering and fluorescence of single nanotubes allows unprecedented spectroscopic study.
9. New Polymeric Materials for Medicine - Professor Mark Grinstaff, Chemistry Department - Organic/Macromolecular Chemistry/Materials. In one of its current research projects, the Grinstaff Group is designing, synthesizing, and characterizing novel dendrimers, termed “biodendrimers,” for tissue engineering and biotechnological applications. Currently, they are evaluating these novel biomaterials for the repair of corneal lacerations, for the delivery of anti-cancer drugs, for the delivery of DNA, and as temporary biodegradable scaffolds for cartilage repair. In a second project, they are creating novel polymeric coatings termed “interfacial biomaterials” that control biology on plastic, metal, and ceramic surfaces. In a third project, they are designing electrochemical-based sensors/devices using conducting polymer nanostructures and specific DNA structural motifs.
10. Bottom Up Strategies (Organic Synthesis) to Construct Carbon Nanotubes - Professor Ramesh Jasti, Chemistry Department - Organic/Materials - In the last twenty years, carbon nanotubes (CNTs) have become molecules of great interest for nanotechnology. Due to their high charge carrying capabilities and tunable band gaps, CNTs have been suggested for the next platform for microelectronics.1 Depending on the arrangement of atoms, carbon nanotubes can be metallic or semi-conducting. In fact, the arrangement of carbon atoms along the axis can even change leading to a metallic-semiconducting molecular junction. The highly interdisciplinary Jasti Group is working at the interface of organic synthesis and nanoscience. They aim to utilize bottom-up strategies (organic synthesis) to construct carbon-based nanomaterials with structural control at the atomistic level. Currently, they are exploring new synthetic methods to prepare carbon nanotubes, graphene, and diamondoids. Their overarching goals are to utilize their precise synthetic methods to study the physical properties of these discrete nanostructures (physics) and correlate them with quantum mechanics (theory). Furthermore, they aim to apply their understanding of these new materials for the development of new nanotechnologies in the areas of energy, electronics, and medicine.
11. Theoretical and Computational Biochemistry Professor Tom Keyes, Chemistry Department - Theoretical Chemistry - My research focus is theoretical biophysical chemistry. Current projects are the mechanism and dynamics of protein folding, binding of ligands to proteins, all-atom descriptions of viruses, and 'theory of experiment' for the associated spectral probes. Overall themes are: 1. the idea that classical mechanics is more broadly applicable than is generally realized, so long as induction, or polarization - the creation of dipoles by local electric fields - is accurately included. Thus we have classical theories of nonlinear IR and Raman spectroscopy and consider that ligand binding occurs via classical 'electrostatic bonds'. 2. formulating theories in terms of the multidimensional potential energy surface, or landscape, and 3. developing intelligent or accelerated simulation algorithms for these computationally intensive problems.
12. Biomechanistic Studies of the Formation of C-P Bond-Containing Natural Products - Professor Pinghua Liu, Chemistry Department – Biological Chemistry - Phosphonates (C-P bond containing compounds) are a unique class of natural products, which can represent up to 10% of the phosphorous-containing metabolites in marine organisms. However, their biosynthesis and biological functions have not been studied. The mechanistic studies on C-P bond-containing natural products in the Liu Laboratory are addressing two fundamental questions: (1) how is the C-P bond formed enzymatically? and (2) how are these phosphonates degraded in nature? The only C-P bond-forming enzyme characterized to date is phosphoenolpyruvate mutase. The analysis of C-P-containing natural products indicates that there must be other enzymatic procedures to form C-P bonds. The REU student in the Liu Group learns a wide range of techniques to study an iron-sulfur cluster-containing methyltransferase, including organic synthesis, molecular biology, and enzymology. The successful studies on several oxygen-sensitive iron-sulfur-containing proteins will serve as the basis for the proposed work of the student on iron-sulfur clusters aimed at understanding the mechanism of C-P bond formation in natural phosphonate synthesis. Since joining BU in 2005, the Liu Laboratory has hosted 15 undergraduates for research. To date, three papers have been published based on the work of undergraduate researchers, including one from an REU summer researcher (2008). Several other manuscripts with undergraduate co-authors are in preparation.
13. Advances in the Stereocontrolled Synthesis of Complex Natural Products - Professor James Panek, Chemistry Department – Organic/Synthetic Chemistry - Research in the Panek Laboratory is centered on the design and development of new methods for the stereocontrolled synthesis of complex organic molecules. Serving as inspiration for reaction development, natural product targets are chosen based on their novel architecture and biological activities. Once the scope of a methodology is determined, it is utilized in the stereocontrolled synthesis of a natural product or a group of related natural product targets. These natural product targets then provide opportunities for the preparation of chemical entities through diversity-oriented synthesis. The objectives are to enhance structural diversity available from Nature and to prepare molecules with novel chemical or biological properties. These studies are often carried out in conjunction with the Center for Methodology and Library Development at Boston University (CMLD-BU). The REU student’s experience would include experiments involving methodology development and the stereocontrolled synthesis of complex natural products. Other options include the synthesis of chemical libraries in collaboration with the CMLD-BU. The REU student would be actively involved in contemporary synthetic methods and using modern analytical techniques.
14. Studies Towards the Synthesis of Complex Molecules -
Professor John Porco, Chemistry Department – Organic/Synthetic Chemistry - Research in the Porco Laboratory (http://people.bu.edu/porcogrp) focuses on two major areas: (1) the development of new synthetic methodologies for efficient chemical synthesis of complex molecules and (2) synthesis of complex chemical libraries, the latter conducted at the CMLD-BU. Synthetic methodologies developed by the Porco Group include: copper (I)-mediated formation of enamides, oxa-electrocyclization/dimerization of dienals enroute to complex epoxyquinoid frameworks; enantioselective oxidative dearomatization using chiral copper complexes and molecular oxygen; photocycloaddition using oxidopyryliums enroute to the rocaglamides and related natural products, and catalytic ester-amide exchange using group (IV) metal alkoxide-activator complexes. In the past 10 years, the Porco Group has synthesized over thirty complex natural product targets, including nine epoxyquinoid natural products, four salicylate enamide macrolides, the rocaglamides, silvestrol, and kinamycin C. The REU project will involve complex natural product synthesis or the synthesis of chemical libraries in collaboration with the CMLD-BU. The REU student would learn synthetic organic techniques, including running reactions under inert conditions, as well as running and interpreting NMR spectra. There have been three REU students (2007, 2008, 2009) who have worked in the Porco Laboratory
15. Synthesis and Characterization of Nanomaterials – Professor Bjoern Reinhard, Chemistry Department - Physical Chemistry - My group designs, implements, and characterizes new tools for imaging and manipulation of "hard" (inorganic) and "soft" (biological) materials. One of our aims is to produce hybrid materials that combine the interesting electronic/optical properties of inorganic materials with the structural properties of biological materials. Potential project include the synthesis of semiconductor and noble metal nanoparticles and their characterization using electron microscopy and single particle spectroscopy.
16. Research in the Chemical and Biological Sciences –
Professor Scott Schaus, Chemistry Department – Organic/Chemical Genomics - The goals of the research conducted in the Schaus Laboratory are to develop new chemical methodologies, to synthesize natural products and small molecules that possess interesting biological activities, and to apply techniques in chemical genomics for studying the effects of compounds on cellular processes. The group uses chemical synthesis, functional genomics, and bioinformatics to gain further understanding into the effects of antiproliferative compounds on cellular processes. The research approach creates an integrated training environment, encouraging students to identify and develop research projects that address fundamental questions in chemistry and biology. The diverse array of research projects undertaken in the Schaus Group work synergistically toward the development of a new asymmetric methodology and its subsequent application as they synthesize interesting natural products and develop and use techniques in genomics and biology to understand how these compounds affect cellular processes. Their work in chemical methodology has focused on the development of direct asymmetric carbon-carbon bond-forming reactions. A reaction they have been studying is the Morita-Baylis-Hillman (MBH) reaction; a long-standing challenge in asymmetric catalysis. Their approach has been to concentrate on the phosphine-promoted reaction. They have successfully identified a highly enantioselective Brønsted-acid catalyzed MBH reaction. The reaction not only addresses a gap in asymmetric synthetic methodology but also identified a unique example of chiral Brønsted acid catalysis. Future work will focus on developing the reaction for use in synthesis. They plan to use the reaction as a key step in the synthesis of the pycnanthuquinones, natural products with a unique mode of overcoming the symptoms of type 2 diabetes mellitus. An REU student working on this project would learn the basic techniques of synthesis and purification, chiral HPLC analysis, preparative LC methods, and multinuclear NMR analytical techniques.
17. Discovery of New Synthetic Methodology for the Development of Biologically Active Small Molecule Libraries - Professor John Snyder, Chemistry Department – Organic/Synthetic Chemistry - The discovery of new drug candidates and biological probes begins with the discovery of new chemistry, leading to new compounds of unusual structure, rich in stereochemistry, that go beyond what nature can devise. The Snyder Group focuses on the discovery of new chemistries for the synthesis of natural product-like scaffolds that can be exploited in the preparation of small molecule libraries. An example is the preparation of a series of tetrahydro-1,6-naphthyridines such as 1 which have shown anti-tuberculoid activity. Another series of heterocycles represented by 2 was discovered to be active against hepatitis C virus. Other projects begin with readily available natural products as scaffolds for diversification to new chemotypes such as 3. The REU student will develop new organic synthetic methodology for the discovery of new biological active compounds. In the course of this research, the scope of the chemistry will be expanded with a greater variety of co-reactants to create a small molecule library. Once prepared, these libraries will be submitted for bioactivity screening through the CMLD-BU for a variety of activities. In the past 5 years the Snyder Group has had 26 undergraduates doing research in their laboratory, including six summer researchers. Seven undergraduates have been co-authors on research publications in this time period. They hosted two of the REU students: Megan Nines (Lock Haven University of Pennsylvania) in 2007, Samantha Carter (Queen Mary, University of London) in 2008, Patrick Deifik (Louisiana-Lafayette) in 2009.
18. Natural Propduct Synthesis - Professor Corey Stephenson, Chemistry Department - Organic Chemistry - The Stephenson Group's research interests include complex molecule synthesis and the development of new synthetic methodologies for the rapid generation or molecular complexity from readily available building blocks.
19. Computer simulation of amyloid peptide aggregation using all atom protein models – Professor John Straub, Chemistry Department – Theoretical Chemistry/Bioinformatics - Human islet amylin polypeptide (IAPP) is a 37-residue peptide produced in the pancreas. Amylin is cosecreted with insulin and its normal function is associated with glucose metabolism. In certain individuals, it contributes to insulin resistance, thereby playing a key role in the initiation of non-insulin-dependent diabetes (type II) mellitin (NIDDM). It is believed that individuals with NIDDM have amyloid deposits formed by the association of human amylin. While human amylin peptide aggregates, rat amylin does not aggregate under similar conditions. Based on sequence comparison between human and rat amylin, it is suspected that the ten residues in the region 20-29 are largely responsible for the association of human amylins. Fragment 20-29 can form fibrilar structures that have a distinct morphology; fragment 30-37 was also shown to be critical for fibril formation. An REU student would be directly mentored by a senior graduate student in the Straub Laboratory in working to simulate the aggregation of human and rat IAPP. A goal of the study will be to simulate the system at length to characterize the conformational fluctuations that may lead to the “nucleation” of secondary structural elements, and to understand in detail the role of sequence in aggregation of the peptide. Simulations of the amylin aggregation equilibrium will be carried out as a function of the temperature and solution conditions. In the course of this project, the REU student will learn to use state of the art computational algorithms and gain experience with the computing resources in the Boston University Center for Computational Science. In the past 5 years, the Straub Group has hosted five summer research students, as well as two undergraduates during the academic year.
20. Substituted polyhydroxylated pyrrolidines as substrate analogs for glycolytic enzymes - Professor Dean Tolan, Biology Department –
Chemical Biology - The Tolan Group research focuses on the chemistry at the active site of the glycolytic enzyme, fructose 1,6-bisphosphate aldolase. The enzyme catalyzes the opening of the hemiketal ring of b-D-fructose-furanose 1,6-(bis)phosphate prior to covalent catalysis resulting in the cleavage of the C3-C4 bond. Little is known about the site or mechanism of ring opening catalyzed by aldolase. They have developed both steady-state and pre-steady state kinetic assays, as well as the ability to determine structures by X-ray crystallography so that they can study this activity of the enzyme. Substrate analogs where the ring cannot be opened are required for this work, which can be synthesized as a deoxy-pyrrolidine ring at the hemiketal carbon. They have previously had extensive experience with REU and UROP summer students working in the laboratory. A previous REU student was involved in the purification and characterization of various forms of the enzyme. Her work was critical for the study of the effects of different substrates and inhibitors on the activity of the enzyme. The REU student in this program would be assigned to an individual series of synthetic steps leading to specific labeling of the carbon skeleton. The synthesis, purification, and product analysis will allow the student to apply her/his basic organic chemistry knowledge to the research laboratory setting. The use of the purified final product in pre-steady state kinetic analysis, X-ray crystallography, and data collection will also be conducted.
21. A structural map of the human genome - Professor Thomas Tullius, Chemistry Department – Bioinorganic Chemistry/Bioinformatics - The hydroxyl radical is a powerful chemical probe of DNA structure, which can be used to obtain detailed information on the structure of long stretches of DNA. The Tullius Group has recently constructed a database of hydroxyl radical-generated DNA structural data. In research supported by the ENCODE Project of the National Human Genome Research Institute of the NIH, they are using this database to make a structural map of the human genome. They are concentrating their efforts on understanding the role of the noncoding regions of the human genome that are involved in the regulation of gene expression, and in directing the architecture of chromosomes. They have recently discovered that the shape of DNA (and not just the sequence of nucleotides) is under evolutionary selection. The structural maps of genomic DNA that this work will produce will add a new dimension to understanding of the workings of the human genome. An REU student would work with graduate students and postdoctoral fellows in the group to add new data to the hydroxyl radical cleavage pattern database by performing the hydroxyl radical DNA cleavage reaction on new DNA sequences using a laboratory robotics system, and analyzing the reaction products using a capillary electrophoresis-based automated DNA sequencing instrument. Ilyssa Ramos and Christopher Konel, previous REU students, made important contributions to the project during their participation in the REU program at BU. An REU student with a background and interest in computers and computation could work with members of the Tullius Group which is part of the Boston University Graduate Training Program in Bioinformatics, to devise new computational methods to find and understand structural patterns in the human genome.
22. New Methodology for Simulation of Very Slow Biological Processes - Professor Feng Wang, Chemistry Department– Theoretical Chemistry/Computer Simulation - One of the research interests of the Wang Group is the development of the Basin Hopping Kinetic Monte Carlo (BHKMC) methodology to simulate slow dynamic processes. Standard molecular dynamics simulations usually cannot properly address processes that occur over a time period of more than a few nano-seconds. This limitation rules out straightforward application of these methods to many biological processes that are taking place at a much slower rate. The Wang Group is developing a method that combines basin hopping Monte Carlo, a transition state search algorithm, and Kinetic Monte Carlo to model very slow reactions. Biological applications of the method include modeling of ion channels and protein-ligand docking. In the flexible protein-flexible ligand docking problem, the docked geometry is usually not known a priori. The theoretical determination of the docking rate of such a process is challenging since most methods that calculate reaction rate would require the prior knowledge of the initial and final structures. The BHKMC method does not require the prior knowledge of the final structure, which makes it a very powerful tool for studying such docking problems. The BHKMC is being implemented and tested on simple model systems in our group. The REU student would learn to use the BHKMC code and to test it by running simulations of ion transport through biological channels and comparing with experimental results.
23. Professor Adrian Whitty, Chemistry Department - Biological Chemistry - Research in my laboratory is directed towards two main problems: (1) Mechanisms of receptor activation and signaling in growth factor receptor systems, and (2) The discovery and characterization of small molecule (i.e. synthetic organic) inhibitors of protein-protein interactions. This latter work will be conducted in collaboration with the CMLD-BU. These two main areas of research share the broad themes of protein-protein and protein-ligand recognition, and how the binding energy that is generated by such intermolecular interaction can be exploited to achieve biological function or inhibition. The lessons learned are therefore broadly applicable to a wide range of biological systems in which proteins interact with each other or with small organic ligands.
24. Professor Yu Brandon Xia, Chemistry Department/Bioinformatics Program - Computational Chemistry/Bioinformatics - The Whitty Group applies computational techniques to study the structure, function, and evolution of complex bio-molecular systems, such as proteins and protein networks. Specific projects include: reconstruction of protein interaction and regulatory networks by genomic data integration; comparative and evolutionary analysis of proteins and protein networks; protein sequence-structure-function relationships; prediction of protein structure and function.
25. Professor Larry Ziegler, Chemistry Department and PhotonicsCenter - Physical Chemistry - The Ziegler Group has three projects on which the REU student can engage in research: “Surface-Enhanced Raman Scattering (SERS) Detection of Pathogens” -- SERS is being exploited for the detection and identification of bacterial cells and viruses. A novel gold or silver nanoparticle substrate has been developed which allows the observation of SERS spectra down to the single cell level, in about 10 seconds of data acquisition time using just milliwatts of incident laser power. The unique vibrational fingerprints allow numerical algorithms to be used for diagnostic purposes much faster than currently employed culturing or PCR based methods. "Ultrafast carrier dynamics in wide band gap semiconductor materials" -- Femtosecond measurements are carried out on wide band gap materials, such as pure and doped GaN in order to learn about the properties of these semi-conductors in their conduction bands. These materials are of importance for the development of blue-UV LEDs, lasers and solar energy devices. Following femtosecond pulse excitation, a large variety of electronic and nuclear frame phenomena spanning time scales from 10's of femtoseconds to 10's of nanoseconds result before equilibrium is re-established in these novel materials. "Ultrafast IR spectroscopy" -- Femtosecond pulses tunable throughout the IR are used to study a wide variety of phenomena using pump-probe and multidimensional techniques. These methods are applied to: a. the study of energy relaxation in water, the most ubiquitous solvent; b. the study of fluctuations in super critical fluids, which are central to understanding their special solvation properties on a molecular level and c. the role of lipids and proteins in unraveling the mechanism of generalized anesthetics.
