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Training Faculty / Research Projects

 
Students will work in the lab for one or both mentors on the research team. For more information about faculty research interests, visit their websites via the links below or by visiting: http://www.vanderbilt.edu/vicb/members.htm
 

 

Synthesis and Evaluation of Chemical Tools for Biology
Mentors: Gary Sulikowski (Chemistry), Dave Weaver (Pharmacology), and Patrick Grohar (Cancer Biology)

Description: REU students will participate in the chemical synthesis of probe molecules, such as dyes, affinity tags, and photoaffinity tags, for studies in neuroscience or cancer biology.

Researcher Skills and Interests: This project is best suited for those students who have taken organic chemistry, including lab. Students should be interested in synthetic organic chemistry, the use of separation/purification techniques (chromatography), analysis (NMR spectroscopy), medicinal chemistry, and in vivo phenotyping.
 

Gary Sulikowski  Dave Weaver
         
 

Molecular Trolling for Point of Care Viral Detection
Mentors: David Wright (Chemistry) and Rick Haselton (Biomedical Engineering)

 

Description: This work will focus on the design of a new diagnostic device for the multiplexed detections of respiratory viruses. Molecular hooks (capture stem-loop hairpin DNA constructs) are directly coordinated at known locations on a gold clad polyester filament. Filament motion is used to troll for and entrain viral RNA present in a test solution. Subsequent to capture, any necessary processing steps are carried-out using pull-through processing and fluorescence reporting. 

Researcher Skills and Interests: This project is ideally suited for the student interested in multiple aspects of chemistry including inorganic chemistry, analytical chemistry, biochemistry and nanotechnology.

David Wright   
       
       
 

Structural Mass Spectrometry Strategies for
Natural Product Discovery

Mentors: John McLean (Chemistry) and Brian Bachmann (Chemistry)

Description: One of the challenging aspects of natural product discovery for identifying new compounds as potential drugs is extracting promising target compounds from complex biological mixtures. The Bachmann laboratory has particular expertise in isolating extracts from cave-dwelling organisms, which will be analyzed using ultrafast (<ms) 2D separations using ion mobility-mass spectrometry (IM-MS). In IM-MS, analytes from complex samples are separated on the basis of both molecular structure and mass, respectively. By isolating those signals that correspond to potentially interesting structures will be guiding in deciding which of 1000s of different molecular species should be targeted to yield novel natural products. 

Researcher Skills and Interests: This project is best suited for those students who have taken analytical, physical, and organic chemistry. Students will use state-of-the-art mass spectrometry instrumentation to collect data and interpret those data using protocols developed from physical chemistry theory.

  Brian Bachmann  
 

 Mass Spectrometry Directed Phosphoproteomics
in Cancer Biology
Mentors: John McLean (Chemistry) and Donna Webb (Biological Sciences)


Description: 
Cell migration plays a pivotal role in diverse biological and pathological processes, including embryogenesis, the inflammatory response, wound repair, arthritis, atherosclerosis and cancer. Post-translational modifications, such as phosphorylation, of critical proteins are emerging as key steps in the regulation of cell migration. Thus, quantitatively assessing changes in phosphorylation of migration proteins should provide significant insight into the regulation of this important cellular process. Recently, mass spectrometry (MS) has come to the forefront of phosphoproteomic quantification, but current methods face significant challenges. To address these limitations, we are developing a technology using new protein phosphorylation labeling reagents that provides simultaneous identification and quantification on a global level, without the need for a priori knowledge of where these events occur. Specifically, this new class of reagents provides rapid identification at a lower cost and with higher sensitivity than contemporary labeling strategies. This research involves using new labeling reagents to derivatize cell lysates and analyzing for protein phosphorylation using state-of-the-art MS instrumentation. 


Researcher Skills and Interests: This project is best suited for those students who have taken analytical, physical, and organic chemistry. Students will use new chemical derivatization techniques and state-of-the-art mass spectrometry instrumentation to collect data and interpret those data using bioinformatic algorithms.

 
 
         
 

Oxidative Stress in Neuronal Cells: the Chemistry and
Biology of Neural Degeneration

Mentors: Ned A. Porter (Chemistry) and Zeljka Korade (Biochemistry)

Description: Smith-Lemli-Opitz syndrome is a devastating developmental disorder that effects about 1 in 10,000 individuals. It results in mental retardation, seizures, failure to thrive. Mortality in the first few years of life is 25-50%. Our hypothesis is that one of the underlying causes of the syndrome is a genetic defect that leads to the formation of toxic metabolites that result in altered neuronal development. The project focuses on the mechanism of formation of the toxic metabolites and the biological activities of those compounds. 

Researcher Skills and Interests: This project is suited for students with a background in organic chemistry and an interest in biological processes.

  Zeljka Korade  
         
 

Synthesis of Chiral Amines for Medicinal Chemistry
Mentors: Jeff Johnston (Chemistry) and Alex Waterson (Chemistry)

Description: Many potential therapeutics are chiral nonracemic small molecules. Racemic small molecules contain an equal mixture of an organic compound present as two enantiomers: non-superimposable mirror images of one another. We have developed new reactions that produce only one of the two enantiomers, and this project entails the preparation of important single enantiomer amines for use in fragment-based screening and medicinal chemistry studies. 

Researcher Skills and Interests: This project is best suited for those students that have completed a full year of organic chemistry and its laboratory - additional laboratory experience in synthetic organic chemistry is advantageous. Students should be interested in synthetic organic chemistry, and the use of separation/purification techniques (chromatography) and analysis (NMR spectroscopy).

 
 
         
 

Chemistry and Screening of Novel Natural Products
Mentors:  Larry Marnett (Biochemistry), and Brian Bachmann  (Chemistry)

Description: This project involves the isolation and identification of natural products produced by soil microorganisms. Phases of this project involve culture and fermentation of microorganisms (primarily soil bacteria), isolation of natural products, structure elucidation and evaluation of cytotoxicity against cancer cells and/or bacteria. 

Researcher Skills and Interests: This project is best suited for those students who have taken organic chemistry including lab. Students should possess and interest in learning the following techniques: fermentaion, isolation of organic compounds using HPLC, and interpreting NMR spectra including two-dimensional NMR.

 Brian Bachmann
 
         
 

Structure and Engineering of  Biosynthetic Enzymes
Mentors: Brian Bachmann (Chemistry) and Tina Iverson(Pharmacology)

Description: We are engineering new biocatalysts for the production of clinically important pharmaceuticals. Using a combination of protein structure guided mutagenesis and "directed evolution" methodologies, we are attempting to find biological replacements for important chemical processes. Ultimately these catalysts may offer "green" and less expensive ways to manufacture life saving drugs. 

Researcher Skills and Interests: This project is best suited for those students who have taken a biochemistry course and have a background understanding and/or direct experience in basic biomolecular methods such as PCR, cloning, protein expression and purification and bioassay.

 Brian Bachmann
 
         
 

Exploring Neutralization of S. Aureus Infections via
Trace Metal Binding by Calprotectin

Mentors: Walter Chazin (Biochemistry) and Eric Skaar(Microbiology/Immunology)

Description: Calprotectin is an integral part of the innate immune response. In tissues infected by bacterial pathogens such as Staphylococcus aureus, calprotectin acts to suppress the growth of the invading organism. We have obtained evidence that the mechanism for the growth suppressing activities of calprotectin involves the binding of essential trace metals such as zinc and manganese that are critical for the organism's cellular metabolism. This project involves testing this hypothesis through the design, production and evaluation of calprotectin mutants that reduce its capacity for binding these essential metals. 

Researcher Skills and Interests: This project is best suited to students that have taken a biochemistry course and who may have knowledge of site-directed mutagenesis by PCR and protein purification. Students should possess an interest in learning state of the art multi-disciplinary research and a combination of the following techniques: bacterial expression and purification of proteins, biophysical analysis using NMR and isothermal titration calorimetry, and cell growth assays.

 
         
 

Protein Adducts Resulting from Lipid Peroxidation
Mentors: Ned Porter (Chemistry) and Daniel Liebler (Pharmacology)

Description: Polyunsaturated lipids undergo reaction with molecular oxygen in vivo and form reactive byproducts that modify proteins. The project focuses on the development of methods to identify these modified proteins and assess the consequences of such modifications. We are particularly interested in how such modifications may impact plasma lipids such as LDL (bad cholesterol) and HDL (good cholesterol). 

Researcher Skills and Interests: This project is suited for students have taken organic chemistry and one year of biological sciences.

 
 
         
 

Novel Schizophrenia Therapeutics Through
Cheminformatics in Drug Discovery

Mentors: Jens Meiler (Chemistry) and Jeff Conn (Pharmacology)

Description: The student will use computational methods to analyze the interaction of chemicals with metabotropic glutamate receptors (mGluR). The objective of these studies is to identify features of the chemical structure that are critical for allosteric regulation of mGluRs and therefore key for a therapeutic activity. The student will use computational docking techniques as well as machine learning approaches (artificial intelligence) to study these structure-activity relations (SAR). Through collaboration with the Conn laboratory results will verified through experimental studies such as mutagenesis of mGluRs. 

Researcher Skills and Interests: This project is best suited for those students for have taken general chemistry, organic chemistry, physical chemistry, and mathematics. Knowledge in computer science is advantageous. Students should possess an interest in learning one or more of the following techniques: machine learning, small molecule docking, pharmacophore mapping, computer programming.

 
 
         
 

Natural Product Synthesis and Biology
Mentors: Gary Sulikowski (Chemistry), Brian Bachmann (Chemistry), and Jonathan Irish (Pathology, Microbiology and Immunology)

Description: REU students will engage in the multi-step synthesis of small molecule natural products of modest complexity. The natural products of interest have demonstrated biological activity and the synthetic scheme will allow access to structural modifications providing analogs for further biological evaluation. 

Researcher Skills and Interests: This project is best suited for those students who have taken organic chemistry including lab. Students should possess and interest in learning the following techniques: interpreting NMR spectra, and organic synthesis.

Gary Sulikowski  Brian Bachmann  
         
 

Quantum Dot Nanoconjugate Imaging of Neural Receptors
Mentors: Sandra Rosenthal (Chemistry) and Randy Blakely (Pharmacology)

Description: In our research we synthesize derivatives of drugs such that they can be attached to fluorescent quantum dots, thereby creating nanoconjugates. These nanoconjugates are then used to image individual nerotransmitter transporter porteins. In this way we can obtain movies of the dynamics of these proteins, which are important in a wide range of mental disorders. 

Researcher Skills and Interests: This project is best suited for a student interedted in synthetic organic chemistry and an interest in biological problems. Student must have completed two semesters of organic chemistry laboratory.

 
 
         
 

Determination of Absolute Stereochemistry of Pharmacologically
Significant Small Molecules
Mentors: Prasad Polavarapu (Chemistry), Craig Lindsley (Pharmacology)

Description: Several drugs are derived from chiral organic molecules and the enantiomers of these chiral drugs have significantly different biological properties. At Vanderbilt several small chiral molecules have been discovered where one enantiomer has favorable biological effects, while the second shows little or weak bioactivity. Unfortunately the absolute stereochemistry of these organic compounds is not yet known. The research group of Polavarapu uses a combination of chiroptical spectroscopic and computational methods to determine the absolute stereochemistry of chiral molecules. Students working in this program will actively engage in the experimental and computational studies to determine the absolute configurations. 

Researcher Skills and Interests: This project is best suited for those students who have taken at least organic chemistry. Interest and background in physical chemistry would be useful. Students will collect experimental chiroptical spectroscopic data, including optical rotation and CD spectra, and analyze these data in conjunction with computational predictions.

 
         
 

Discovery and Synthesis of New Antibiotics
Mentors: Gary Sulikowski (Chemistry), Eric Skaar (Microbiology & Immunology)

Description: REU students who contribute to this project will focus on the multi-step synthesis of small molecules. Students will learn to design and synthesize molecules to improve biological potency within a chemical series. Our goal is to establish structure activity relationships (SAR) across several series and discover a tool compound for biological target identification of a new class of antibiotics. 

Researcher Skills and Interests: This project is best suited for those students who have taken organic chemistry including lab. Students should be interested in synthetic organic chemistry, the use of separation/purification techniques (chromatography), analysis (NMR spectroscopy) and medicinal chemistry.

 Gary Sulikowski
 
         
 

Novel Obesity Therapeutics through Cheminformatics
in Drug Discovery
Mentors: Jens Meiler (Chemistry), Dave Weaver (Pharmacology)

Description: The student will use computational methods to analyze the interaction of chemicals with neuropeptide Y4 receptor (Y4). The objective of these studies is to identify features of the chemical structure that are critical for allosteric regulation of Y4and therefore key for a therapeutic activity. The student will use computational docking techniques as well as machine learning approaches (artificial intelligence) to study these structure-activity relations (SAR). Through collaboration with the Weaver laboratory results will verified through experimental studies such as mutagenesis of Y4.

Researcher Skills and Interests: This project is best suited for those students for have taken general chemistry, organic chemistry, physical chemistry, and mathematics. Knowledge in computer science is advantageous. Students should possess an interest in learning one or more of the following techniques: machine learning, small molecule docking, pharmacophore mapping, computer programming.

  Dave Weaver