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www.ncprojectseed.org
NC Project SEEDAnnual Report
2007-2008
Melony Ochieng
Recipient of the 2008 NC Project SEED Essence of The Sisterhood Award as the Outstanding Model Student
www.ncprojectseed.org
Mission StatementNC Project SEED ProgramOur mission is to recruit, financially support, and encourage, talented disadvantaged North Carolina high school students to pursue terminal graduate and professional school degrees in chemistry and chemistry-related science disciplines. NC Project SEED will achieve this goal by providing a comprehensive scientific research internship experience.
We define disadvantaged as:• students from households with a low family income
(as determined by the ACS), or
• underrepresented minority (African-Americans, Latinos, and Native Americans) in science and engineering fields, or
• first generation of their family to attend college, or
• students from schools designated as priority schools by the Manning ruling
Table of Contents
Overview 1
Activities 1
Student Participation 1
Samples of Student Work 1
Staff and Program Management 1
NC Project SEED International 1
NC Project SEED Alumni 1
Reflections 1
Appendix-Fiscal Expenditures 1
4
The Hamner Institutes for Health
Sciences provides administrative
resources and support with
computer facilities, office space,
library resources, conference center
resources and access to staff
members skilled in government grant
administration and reporting. The
Hamner occupies a main building
of 110,000 square feet and a new
laboratory annex of 28,000 square
feet on a park-like, wooded site of 56
acres in Research Triangle Park, North
Carolina.
For over a quarter of a century
The Hamner has been training the
scientists of tomorrow. Its education
programs have provided well-prepared
researchers for the chemical and
pharmaceutical industries, government
research and regulatory agencies, and
universities around the world. The
Hamner offers postdoctoral fellowships
and traineeships, predoctoral
fellowships, and research experiences
for undergraduate students.
Corporate Sponsers
The American Chemical Society is a
non-profit professional organization
that consists of over 151,000
members. The ACS promotes the
public’s perceptions and understanding
of chemistry and the chemical
sciences through public outreach
programs, a public awareness
campaign, career development
assistance, and employment
opportunities for students and
professionals in academia and private
industry. There are 188 Local Sections
of the ACS across the United States.
Local Sections enable members
to communicate and interact with
other chemists in their area and
contribute to the public understanding
of chemistry in their communities.
The North Carolina Local Section is
the largest affiliate in the state of
North Carolina and covers the entire
Research Triangle Area.
The Burroughs Wellcome Fund,
an independent private foundation
dedicated to advancing the medical
sciences by supporting research
and other scientific and educational
activities has made possible the
statewide residential expansion of the
NC Project SEED Program. The number
of student participants increased and
the quality of enrichment activities
improved to provide the most
comprehensive learning experience
in scientific research experience
possible.
NC Project SEED Program Overview
We have a demonstrated
model that works in moving
gifted students into the
sciences.
NC Project SEED places talented disadvantaged North Carolina high school students in academic, industrial, and government research laboratories during the summer to experience “hands-on” research and provides additional academic enrichment and support activities throughout the year. Each student completes a chemical research project under the supervision of a principal investigator (PI) and receives an educational award, SAT preparation, college counseling and scholarship opportunities. The 2007-2008 (17th) edition of this program was highlighted by the expansion of this program from a local commuter program to a statewide residential and commuter program. The residential students were housed at Duke University through the Duke Youth Programs.
5
Research Laboratory FacilitiesDuke, the University of North Carolina
at Chapel Hill (UNC-CH), and North
Carolina State University (NCSU) are all
major Research I category institutions
with facilities that are ranked among
the best in the world. The Hamner
Institutes for Health Sciences has
trained scientists for over a quarter of
a century.
Activities
SEED Academy for Leadership Training and Science (SALTS)Held at The Hamner, topics covered
include Oral Presentations, Poster
Presentations, Bioethics, Scholarship
Counseling, and Careers in Chemistry.
During the academic year, meetings
occur one Saturday per month.
Program Summer SymposiumThe student participants presented
their research findings at The Hamner
on August 2-3, 2007. Each student
presented their findings in a 10 minute
oral presentation.
Awards CeremonyThe Awards Ceremony recognizes the
students for achievements in Science
Competitions, Outstanding SAT Scores
and completing the program and
salutes the departing seniors.
Student SuccessOver the past 16 years, the NC
Project SEED program has served
approximately 100 students with 96
percent attending college (100 percent
over the last five years), 83 percent
majoring in science or mathematics,
67 percent in chemistry, and 75
percent overall receiving full or partial
scholarships. The NC Project SEED
program has more underrepresented
minorities as national winners than
any program in the state and very
possibly the country. Over the past
six years, our students have placed
and won in 36 national awards in
science competitions including eight
Siemens Westinghouse National
Semifinalists and two Sigma Xi
National First Place Winners. Among
our program alumni we currently have
15 students that have been accepted
into science doctoral programs. We
have a demonstrated model that works
in moving gifted students into the
sciences.
OrientationThe students and parents received
an orientation that provided them
with staff introductions, program
expectations, program rules and
regulations, student contracts, and
an initial session of Research 101.
Parents are also inducted into the
PRESS Club
Parental Responsibilities in the Education of SEED Students (PRESSEach site will have a PRESS Club.
The purpose of this club is to involve
parents more often and meaningfully
in the education of their children. The
PRESS Club, the Site Coordinators,
the Scholarship Coordinator and the
Director will work cooperatively to help
ensure that participating students
achieve their academic pursuits and
meet their career goals.
NC Project SEED Cup Winners-The Cup is presented to the most outstanding site in the program. UNC-Chapel Hill site has won this award for seven straight years. Pictured left to right is Mr. Micheal Cherry site coordinator, First row Rachel Costin, Amanda Reames, Christa Goldmon. Back Row Camille Girt, Melanie Ochieng, Melanie Wiley and Sara Weaver.
6
Science Conferences and CompetitionsThe student’s paper provides the
foundation for the oral presentation
and poster session. These follow-up
activities will allow the students to
build upon their summer experiences,
sustaining the intensity during the
academic year. Attendance at these
conferences and competitions will
allow students to interact and network
with other scientists and students.
Members of these organizations
provide the students with role models
and important contacts for advancing
their careers. Students develop and
gain confidence in their research
and presentation skills through their
experience at these meetings.
Student SelectionAnnouncements of the program
were provided by the program to the
participating schools for distribution
to high school counselors. Eligible
applicants are those students that
will meet guidelines established
for the NC Project SEED program.
The students applied online at our
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SAT PreparationPrinceton Review SAT Preparation
courses were provided to our students
to achieve the highest scores possible,
resulting in greater scholarship
opportunities.
Activities, contd.
Field TripsThe Meyerhoff Scholarship Program
at University of Maryland, Baltimore.
Students received inspiration and
motivation from Mr. LaMont Toliver,
Director of the Meyerhoff Scholarship
Program. Over ten of our students have
matriculated to this program.
The John Hopkins Medical Center to
view the portrait of Vivien Thomas, the
subject of the book “Partners of the
Heart" which was required reading for
our participants.
The National Institutes of Health
to explore scholarship and research
opportunities for our students. Two
of our former SEED students were
present as participants of the NIH
Undergraduate Scholarship Program.
website (www.ncprojectseed.org). The
student applications were organized
by the Scholarship Coordinator, Ms.
Faye McNeal and screened by the NC
Project SEED Staff.
The initial screening criteria will include
the students grade point average,
grades, End-of -Course Test Scores,
Honors and Awards, Extra-Curricular
Activities, a writing sample, and current
Science Teacher Recommendations.
The top applicants will be invited to an
interview by committee and then final
selections will be made.
This year we incorporated the expertise
of our Scholarship Coordinator, Ms.
Faye McNeal. Ms. McNeal has over 25
years experience as a counselor. As a
result, we had the highest number of
applicants we have ever had with over
200 applicants for 30 spaces. Each
applicant was interviewed, and our final
selections were made. Of the students
selected, three were ranked number
one in their class and 90% were
ranked in the top 15% of their class.
Carlos Fonseca with his poster at the NC OPT ED Alliance Day poster session.
Christa Goldmon prepares her research paper.
7
Name School City/State School District Grade
Duke University Affleck, Arthur Jordan Durham, NC Durham 11
Bazemore, Kristen Bertie Windsor, NC Bertie 11
Black, Danielle New Hanover Wilmington, NC New Hanover 11
Bunch, Lauren Bertie Windsor, NC Bertie 11
Chesney, Rakeem North Moore Robbins, NC Moore 11
Copeland, Hardy Warren County Warrenton, NC Warren 11
Fulton, Shaun Parkland Winston-Salem, NC Forsythe 10
Lochlear, Ursala Purnell Swett Pembroke, NC Robeson 11
Newell, Brittany Lumberton Lumberton, NC Robeson 11
Peebles, Catherine Northampton-West Gaston, NC Northampton 11
Ramsey, Charles Hertford Murfreesboro, NC Hertford 10
Sanchez, Michael Northside Jacksonville, NC Onslow 11
Smith, Andy *NCSSM Gaston, NC (home) Northampton 11
NC State University Fonseca, Carlos Millbrook Raleigh, NC Wake 11
Holland, Christopher Enloe Raleigh, NC Wake 11
Logan, Michael Enloe Raleigh, NC Wake 11
Townes, Allison Enloe Raleigh, NC Wake 10
Wilson, Charnelle Sanderson Raleigh, NC Wake 10
Wyche, Kelly Broughton Raleigh, NC Wake 10
Young, Brandon Enloe Raleigh, NC Wake 10
UNC-Chapel Hill Costin, Rachel Southern Durham, NC Durham 11
Gillespie, Jharrison Hillside Durham, NC Durham 10
Goldman, Christa Jordan Durham, NC Durham 10
McDonald, Evangelina E. Chapel Hill High Chapel Hill, NC Chapel Hill/ Carrboro City 10
Ochieng, Melony Jordan Durham, NC Durham 11
Reams, Amanda Chapel Hill Chapel Hill, NC Orange 10
Weaver, Shara Josephine Dobbs Clement Durham, NC Durham 10
Early College High School
Wiley, Melony *NCSSM Burlington, NC (home) Alamance 11
Program Finalists
*North Carolina School of Science & Math
8
University Admissions and Scholarships for 2007-2008Name College & University Scholarships Total Total Scholarships Admissions* Received Amount Received
Affleck, Arthur University of Miami Hampton University Merit $6,000 $6,000 Florida State University North Carolina State U. Bazemore, Kirsten UNC-Chapel Hill $203,050 Converse College Merit $44,000 Campbell University Presidential $51,800 Wake Forest University University of Maryland-BC Agnes Scott College Merit $48,000 Meredith College Merit $26,000 Catawba College Merit $22,000 Aubrey Lee Brooks $8,000 Aubrey Lee Brooks Computer Allowance $3,000 NAACP Book Award $250 Black, Danielle Duke University Merit $161,476 $551,740 Drew University Presidential Excellence $80,800 Kean Minority Endowed Scholarship $14,000 Johnson & Wales Merit $28,000 UNC-Chapel Hill Merit $10,000 Winston Salem State Merit $19,852 Miami University Miami Excellence Award $10,000 Oxford Scholars $4,000 Redhawk Scholars $16,000 Venture Scholars $20,000 Miami Scholars Award $12,000 Swarthmore College Merit $175,612 Johnson C. Smith Chesney, Rakeem Wake Forest University Merit $212,124 $364,124 Elon University Watson Scholarship $108,000 Elon University Presidential $18,000 UNC-Greensboro Teaching Fellows $26,000 Elizabeth City State U. North Carolina State U.
Costin, Rachel North Carolina Central University BRITE Scholarship $56,000 $58,200 Hampton University 100 Black Men of America $2,000 Howard University AKA Scholarship $200 Elizabeth City State Fayetteville State U. Winston Salem State U. UNC-Greensboro Campbell University Spelman College Liberty University Goldmon, Christa UNC-Charlotte LCOP /MSEN $24,000 $32,000 UNC-Greensboro Jabberwock $8,000 UNC-Wilmington NC A & T State University Fonseca, Carlos University of Maryland-BC Meyerhoff $88,000 $108,000 Presidential $20,000 Locklear, Ursala Campbell Merit $30,000 $34,500 Merit $4,000 UNC-Pembroke Native American $500 Logan, Michael UNC-Greensboro UNC-Charlotte
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Name College & University Scholarships Total Total Scholarships Admissions* Received Amount Received
McGirt, Camille Hampton University Merit $24,000 $315,000 Hampton University Basketball $100,000 Dartmouth Basketball $150,000 Temple Merit $30,000 AKA Scholarship $4,000 UNC-Chapel Hill Wendy's Heisman $100 Spelman College AKA Academic Scholarship $500 UNC-Greensboro Natational Council of Negro Women $800 Links Scholarship $600 William R.Hearst MSEN $5,000 Ochieng, Melony North Carolina Central University BRITE Scholarship $56,000 $56,000 UNC-Greensboro University of Maryland-BC Oxford College of Emory U. Peebles, Catherine North Carolina State Seton Hall Merit $44,539 $44,539 North Carolina Central UNC-Charlotte Fayetteville State Sanchez, Michael Stanford University Merit $183,520 $382,840 North Carolina State College of Physical $20,000 & Mathematical Sciences Duke University $179,320 UNC-Chapel Hill University of Maryland-BC Brown University Columbia University Wake Forest University Emory College of Emory U. Oxford College of Emory U. Vanderbuilt University Williams College Bowdoin College
Smith, Andy Duke University Merit $179,320 $566,320 University of Maryland-BC Meyerhoff $88,000 UMBC Honors College Presidential $20,000 UNC-Chapel Hill Merit $30,000 John Hopkins Merit $204,000 North Carolina Central U. Soaring Eagle $40,000 North Carolina Central U. Soaring Eagle - Stipend $4,000 North Carolina Central U. Soaring Eagle - Laptop $1,000 Wiley, Melanie University of Maryland-BC Meyerhoff $88,000 $153,000 Presidential $20,000 North Carolina Central Soaring Eagle $40,000 North Carolina Central Soaring Eagle - Stipend $4,000 North Carolina Central Soaring Eagle - Laptop $1,000 UNC-Chapel Hill East Carolina University
Total Value $2,875,313 $2,875,313
10
Charnelle L. WilsonEffects of Dicyclopropenylmethylxane on the Counteracting responses of Ethylene in Musa paradisiacalSupervisor: Dr. Edward Sisler, North Carolina State University, Department of Molecular and Structural Biochemistry
Spoilage of plants is a major issue in the farming industry. Annually, 25 percent of post harvest crops world wide become spoiled before they hit the market. Thus, with the newly developed compound, dicyclopropenylmethylxane, the objective is to find the minimum concentration, chemical state, and strategies needed to keep outdoors plants from spoiling. Dicylcopropenylmethylxane is not yet patented, therefore its exact chemical properties can not be revealed.
Musa paradisiaca, or bananas, was used in this experiment to test the compound at various chemical phases. During each experiment, ethylene
was used to trigger the ripening process to determine if the compound bound to the receptor. In addition to the chemical state, various variables were tested to see if it affected the outcome. Incubation time, amount of Tween 20, and ethylene treated at zero time were major variables that affected the outcome of the results.
By testing various concentrations it was found that 10 micro liters per liter of the dicyclopropenylmethylxane was the minimum concentration needed if used as a gas or liquid. Due to the banana having a thick peel, they softened when the compound was used as a liquid.
Brandon F. YoungFinding Activators for Procaspase-3 ProteinSupervisor: Dr. Clay Clark, North Carolina State University, Deptment of Molecular and Structural Biochemistry
Apoptosis, or programmed cell death, occurs in response to cytotoxic stimuli that leads to the dismantling of the cell. The absence of apoptosis leads to tumorogenesis, which implicates the proteins in apoptosis as good cancer targets. Pieces that play an integral role in apoptosis are Caspases which are a family of cysteine-dependent aspartate-directed proteases. Seven of the eleven known human caspases are used in apoptosis; these seven are divided into two sections, initiators and effectors. Initiator caspases such as Caspases -2, -8, -9, and -10, react to signals to initiate the cleavage of effector caspases -3, -6, and -7, which, in turn cleave different cellular substrates necessary
This was not seen as big concern mainly because flowers and other ethylene sensitive products may not have thick outer coverings.
Using 10 micro liters of the compound solution it was concluded with over 24 hours of incubation time and use of carbonic acid in the aqueous solution, the product resisted ethylene action. In the future there should be more repeated trials to ensure these results.
for cell death. In cancer cells there is an increase in the concentration of effector caspases such as procaspase-3, because it is unable to be cleaved due to some dysfunction in the cascade upstream of its activation. The activation of procaspase-3 by a small molecule in cancer cells would have a profound impact on cancer therapy. Current studies focus on confirming previous results that PAC-1 is a valid activator of procaspase-3, optimizing a high through-put assay for testing other potential activators, and ultimately examining the protein-protein interactions between PAC-1 and procaspase-3.
Student Projects
11
Purpose: The fungus Rhizoctonia solani causes disease in vegetation especially plants within the Solanaceae family which includes tomato, potato, tobacco, and many other vital crop plants. The R. solani fungus produces the metabolite, Phenyl Acetic Acid (PAA), which penetrates the plant’s cell wall and cell membrane and causes infection. The fungus produces PAA through the shikimate metabolic pathway, a pathway that is also used by the plant to produce PAA as a growth hormone. Interestingly, the fungus also metabolizes through the quinate pathway which is induced by the presence of Quinic Acid (QA). Intriguingly, these two metabolic pathways share two intermediates—dehydro shikimate and dehydro quinate. It has been shown through past research that the addition of QA to a plant’s growth medium incites the quinate pathway, thus withdrawing the shared intermediates from the shikimate pathway and decreasing the production of PAA. Based on such research, QA is being considered as a means of managing the Rhizoctonia disease, however the effects of QA on plant growth has not been noted. Also knowledge of
Christopher D. HollandTomato Seedling Growth in Response to Various Concentrations of
Phenyl Acetic Acid and Quinic AcidSupervisor: Dr. Marc Cubeta, North Carolina State University, Plant
Pathology Department, Center for Integrated Fungal Research
PAA’s effects on plant health is not known. Through the following research, it is intended to show the maximum concentration of QA that can be used in an in vitro growth medium until plant growth negatively responds. This research is also intended to determine the maximum concentrations of PAA that will not cause plant growth inhibition.
Methods: Tomato seedlings were isolated in an in vitro experiment in which they were grown on a water agar growth medium. Various concentrations of PAA and QA were added to the growth medium. There were eight concentrations for each compound, QA and PAA. Concentrations for QA include: 0, 5, 15, 25, 50, 75, 100, and 150mM. Concentrations for PAA include: 0, 0.1, 0.25, 0.5, 0.75, 1.0, 1.5, and 2.0mM. There were four replicate boxes (tissue culture vessels) for each treatment (concentration) of the two chemicals; each box with a total media volume of 50ml. In each replicate box there were eight seeds. Seeds were then incubated for 10 days and observed for germination and plant height on
the following days: Day 1, 4, 6, and 8. Statistical analysis was then taken on the germination and height data.
Results: Based on the data from this experiment plant growth negatively responds to QA at concentrations 100mM and higher. Plant growth negatively responds to PAA at concentrations 0.5mM and higher. Plant germination in response to QA is prolonged slightly; however germination in response to PAA is more drastically prolonged.
Conclusions: This experiment shows at high concentrations of QA and PAA plant growth can be inhibited. QA could be used as a means for managing the Rhizoctonia disease but there is a maximum concentration that if exceeded in use it could be detrimental to plant growth. Also through this experiment it is evident that at very low concentrations PAA could stimulate plant growth. However, at concentrations of 0.75mM PAA is sure to cause damaging effects to plant growth.
The purpose of this experiment was to alter the foaming and interfacial properties of beta-lactoglobulin protein (the most abundant protein in whey protein). The alteration of its foaming and interfacial properties could result in this protein being able to be used in a larger variety of foods.
We were attempting to find if copper sulfate would change the properties of this protein, and which concentrations would have the best results in the foaming and interfacial properties. The six
Kelly WycheThe Effect of Copper on Beta-lactoglobulin
Air-Water Interfaces and FoamsSupervisor: Dr. Allen Foegeding, North Carolina State University
Department of Food Science
concentrations used were 0 mM, our control, 1 mM, 4 mM, 7 mM, 10 mM, and 13 mM copper sulfate; 10% Beta-lactoglobulin was used for all of the treatments. We measured 3 foaming properties: the overrun, or gas incorporated into the foam, the yield stress, or force required to rupture the foam, and the drainage time, or time required for the foam to breakdown. We measured two interfacial properties: surface tension, or ability of proteins to unfold at the interface, and dilatational elasticity, or the ability of the proteins to bond at the interface. We then ran
electrophoresis to measure the dimers that formed for each different copper treatment.
The data collected showed that copper sulfate had a significant effect on all of the following properties, however there was not a pattern as to which one concentration had the most changes to these properties. Therefore, it was concluded that copper sulfate did alter the foaming and interfacial properties of beta-lactoglobulin protein, and it was inconclusive which concentration altered these properties the most.
Student Projects
12
Carlos FonsecaGrowth Conditions of Yellow Fever Recombinant Escherichia ColiSupervisors: Dr Donald Brown and Dr. Racquel Hernandez, North Carolina State University, Department of Molecular and Structural Biochemistry
The purpose of this experimentation is to determine if Polyethylene oxide (core) chitosan (sheath) nanofibers can be formed while determining the characteristics of the nanofibers. In determining this, the method of core-sheath electrospinning is used. Electrospinning is the process in where an electrical potential is used to produce a fine mat of fibers. Several methods are used in determining the characteristics of the fibers. Scanning Electron Microscopy (SEM) is used to produce 3-dimensional images of the fibers for further characterization. Fourier Transform Infrared Spectroscopy (FTIR) allows the core-sheath electrospun samples to be analyzed in order to
Michael B. LoganElectrospinning and Characterization of Polyethylene oxide (core) Chitosan (sheath) NanofibersSupervisor: Dr. Russell E. Gorga, North Carolina State University, Department of Textile Engineering
Yellow fever virus is a member of the Flaviridae family and is reported by the World Health Organization to produce 300,000 cases annually. The genome of yellow fever virus (YF) is composed of a single strand of RNA. Due to the RNA molecular composition of uracil, it is often difficult to study using standard protocols. In order to facilitate research by the production of a more stable template, RNA underwent reverse transcription forming cDNA. The cDNA is then used to create recombinant plasmid DNA and later inserted into Escherichia coli bacteria.
The purpose of this research is to determine a procedure that would yield optimal high quality amounts of DNA from the Escherichia coli bacteria. Escherichia coli bacteria were grown in different culture media as well as different antibiotic concentrations. The plasmid DNA from the bacteria was extracted, purified, and analyzed to develop a procedure to produce the highest quality and quantity of YF cDNA.
determine what elements are contained in the fibers. Transmission Electron Microscopy (TEM) analyzes the nanofibers and determines if co-axial fibers are formed.
The SEM images of the fibers prove that as the working distance (distance from the electrospinning apparatus to the collector plate) is increased from 10cm to 20cm the fiber diameters decrease in size. It is shown that at a working distance of 15cm with an electrical charge of 20 kilovolts, ideal fibers are formed. FTIR provides proof that Polyethylene oxide (PEO), chitosan, and acetic acid are contained in the fibers. TEM supports the hypothesis that core-
sheath fibers can be formed in which Polyethylene oxide represents the core and chitosan represents the sheath. Future studies should be conducted to remove residual acetic acid in order to maintain the integrity of the fibers.
Student Projects
13
Allison TownesBinding of Perfluorinated Compounds to Human Serum Albumin
(HSA): A Molecular Modeling StudySupervisor: Dr. Melissa A. Pasquinelli, North Carolina State University,
Department of Textile Engineering, Chemistry, and Science
We all know that our nations energy reserves are in short supply however, there is a near unlimited supply of energy coming from the sun but we have inefficient ways of making that energy useful. Therefore, we create these Ruthenium Bipyridine Complexes and place them with lysine amino acids inside coiled-coil helices because they offer good energy transfer. These compounds were created by a synthesis scheme with a starting material of Bipyridine. Then, the bipyridine was further synthesized to an aldehyde, carboxylic acid, and leading to a Ruthenium complex. After the compounds were complete they were ran through TLC test, UV-spec test and percent yields were taken.
The data showed that the compounds had the appropriate percent yields according to our review of literature. The TLC test showed that the percent yields were in good quality do to there Rf values in reference to the literature. The UV-specs showed that the compounds had the absorbed the correct amounts of light do to its maximas in reference to the literature also. Therefore we can conclude that our synthetic scheme was correct and that this Ruthenium Complex can reach the next steps for energy transference and later alternative renewable resources.
Perfluorinated compounds (PFCs) are comprised of a chain of carbon atoms that are saturated with fluorines and are typically capped with an acid. PFCs are ubiquitous; they are found in wildlife, nature and humans throughout the world. In the human body, perfluorinated compounds have a mean serum half-life of 8.67 years. This research project used molecular modeling tools such as molecular docking to predict if the long serum half-life of PFCs is related to how PFCs bind to either or both of the two binding sites of the most abundant blood plasma protein, human serum albumin (HSA).
The molecule set that was docked into both site I and site II of HSA included nine PFCs, nine molecules with hydrogen atoms replacing all the fluorine atoms of PFCs, and molecules with known binding affinities. The results indicate that docked ligands form a variety of hydrogen bonds with different amino acids, and that PFCs bind well to both sites, but prefer site II. In addition, the docking scores for PFCs are higher than their hydrogen counterparts which are comparable to the fatty acids that commonly bind to HSA, indicating a plausible explanation for the persistence of PFCs in blood plasma.
Carletta MuseThe Synthesis of Ruthenium Bipyridine Complexes Coupling to a
Lysine Amino AcidSupervisor: Dr. Marcey L. Waters, University of North Carolina
at Chapel Hill, Department of Chemistry
Student Projects
14
Camille McGirtSynthesis of Pyrene and Fluoranthene Polycyclic Aromatic Hydrocarbons to Quinones and Catechols, and Toxicity of Microbial Biodegradation Metabolite Products (A Two-Year Study)Supervisor: Dr. Louise M. Ball, University of North Carolina at Chapel Hill, Department of Environmental Engineering
Thomas ShanklinSynthesis of N, N’-(hexane-1,6-diyl)bis (4-(2-methoxyphenyl)piperazine-1-carboxamide) for Measuring Dermal and Inhalation Exposure to IsocyanatesSupervisor: Dr. Louise M. Ball, University of North Carolina at Chapel Hill, Department of Environmental Engineering
Pyrene and fluoranthene are compounds that belong to the Polycyclic Aromatic Hydrocarbon (PAH) family. PAHs are known to be mutagenic and or carcinogenic, they are also suspected to harmfully affect the reproductive process. In microbial biodegradation PAHs are naturally metabolized into their quinone and catechol state. These metabolites (quinones and catechols) are also believed to display some forms of toxicity and are believed to kill microbes while in the detoxification process.
In the first year of this study we attempted to synthesize fluoranthene (parent compound) into its -2, 3-quinone (Ceric ammonium Sulfate) state and oxidize a portion of the quinone into its catechol state. We also attempted to do the same for the pyrene PAH (-4, 5- quinone [Ruthenium III Chloride] and catechol). The second year the effects of their metabolites on E. coli C3000 was studied. The effects were determined by the amount of killing exhibited from the quinone and catechol in comparison to the E. coli and solvent control group.
The fluoranthene-2, 3-quinone and catechol were successfully synthesized, as well as the pyrene-4, 5- quinone and catechol. There was minimal to no killing that took place in the E. coli experiment. The solvent used was DMSO (dimethyl sulfoxide); it is believed that if a stronger solvent and higher dosages of the quinone and catechol were used then more killing of the E. coli would have taken place.
The quinones and catechols were tested using an H-NMR and Mass Spectra to check the purity and validity of the compounds.
Isocyanates are a group of highly reactive and highly toxic chemicals. These isocyanates are the leading cause of occupational asthma worldwide. Much work is being done to prevent the exposure of these chemicals, such as Personal Protective Equipment and safer handling procedures. However, despite efforts to prevent exposure, isocyanates are still exposed to workers, through inhalation and through absorption through the skin. Researchers have been working to come up with methods to measure the amounts of isocyanates being exposed to workers. The experiment was designed to create a pure urea derivative of a isocyanate to help create a linear standard curve of isocyanate exposure. The urea derivative was created from the reaction of 1,6-hexamethylene diisocyanate, the isocyanate, and 1-(2-methoxyphenyl)piperazine, derivatizing reagent. The reaction was performed
using the solvent DMSO. The purity of the HDI derivative was analyzed through NMR Spectroscopy; the data recorded showed that the derivative was pure. The molecular mass of the HDI derivative was measured through Mass Spectroscopy, and the molecular mass was 552 u, which was the same as the molecular mass recorded through the NIOSH method 5521.
Student Projects
15
Amanda ReamsThe Development of a Hydrothermal Method for Synthesizing Zinc
Oxide (ZnO) Nanowires and NanoflowersSupervisor: Dr. J. Papanikolas, University of North Carolina
at Chapel Hill, Department of Chemistry
Christa Charisse GoldmonStructural Basis of Eglin C’s Conformational Dynamics
Supervisor: Dr. Garegin Papoian, University of North Carolina at Chapel Hill Department of Chemistry
Purpose: Due to the big push to improve the increasing energy crisis in the world many different alternative electricity sources are being used. Some of these alternatives include wind power, fuel cells, and photovoltaics. Of these three, photovoltaics seem to be the most promising in the future. Photovoltaics use one main system that will be beneficial to this research. Thin Film Cell photovoltaics use nanostructures to increase the solar cell’s surface area. When surface area is increased more energy, in the form of light, can be absorbed to produce more electricity. The purpose of this research is to develop a hydrothermal method that will be used to successfully synthesize Zinc Oxide (ZnO) nanowires and nanoflowers. Once the method is determined the nanowires
can be used to help further the understanding of nanostructures and their role in photovoltaics.
Methods: Zinc Nitrate and Hexamethylenetetramine were prepared under hydrothermal synthesis to produce ZnO. Zinc Oxide was prepared by using three different solution concentrations, two different reaction times, and two different reaction temperatures. Zinc Oxide was deposited onto two glass substrates during incubation. After incubation ZnO was dried in air at room temperature and later used for Scanning Electron Microscopy (SEM) for characterization.
Results: Final SEM characterization showed that ZnO nanowires/flowers were produced at 0.01 M
and 0.001 M for three hours at 150°C. Formation of nanowires/structures was less dense at 0.001 M, but was the same size and shape as nanowires/flowers produced at 0.01 M. When solution was 0.1M there was little to no formation of nanowires.
Conclusions: These experiments show that the formation of nanowires/flowers was best at lower concentrations, lower reaction times, and higher temperatures. Formation of nanowires was dependent on solution concentration, reaction time, and reaction temperature. The results are consistent with the idea that varying different parameters can affect the density and final morphological character of ZnO.
Molecular Dynamics (MD) is used to supplement experimental results because it can provide atomistic detail to the system of interest. MD is being used by chemists and biochemists, and has become an important tool in the investigation of biomolecules. Proteins are an important class of biomolecules and their study is essential for understanding of life processes. In this study basins in the energy landscape of protein Eglin C will be structurally evaluated.
Visual Molecular Dynamics (VMD) is the visualization tool used to examine molecular dynamics trajectories. Samples of basins obtained from a Principal Component Analysis of the MD trajectory were extracted using VMD. A program which identified contacts between residues was used to analyze the nature of basin.
Within each basin there are certain significant contacts which appear in over fifty percent of the snapshots. These contacts constitute the essential contacts of these basins. Although, the majority of significant contacts found are hydrophobic in nature there are several important hydrophilic contacts and salt bridges present.
These experiments show that when different basins fluctuate around a single minimal energy structure the significant contacts are similar. They are fluctuating around a single minimal energy structure because they share significant contacts. There are several important hydrophilic contacts within each basin therefore, the recent literature of protein surfaces are correct.
Student Projects
16
Jharrison GillespieThe Effect of Templates on the Formation of HydrazonesSupervisor: Dr. Michel R. Gagne, University of North Carolina at Chapel Hill, Department of Chemistry
Evangeline Lea McDonaldThe Effects of the Overexpresion of Mitochondrial LepA on the Growth of E. coli CellsSupervisor: Dr. Linda Spremulli, University of North Carolina at Chapel Hill Department of Chemistry
LepA is believed to be an elongation factor which back-translocates any ribosome which is improperly translocated during protein synthesis. The effects of mitochondrial LepA on E. coli cells are not yet known. The main goal of this project is to further understand protein synthesis by exploring the effects of mitochondrial LepA on E. coli cell growth.
Mitochondrial LepA’s DNA was purchased and cultures of E. coli carrying the Lepa gene were created. Aliquots were taken and put into flasks with LB. They were grown and absorbance was measured with a VIS spectrophotometer. The cells
were induced with IPTG. When both saturated, aliquots of these were taken for a 20x dilution and cells were grown again with LB and IPTG.
It was found that when LepA was expressed normally, its growth curve pattern was similar to BL21 although it had a longer lag phase. When induced, LepA entered a stationary phase very quickly. After they were diluted, BL21 cells began to grow again while growth in LepA was much slower.
The results from multiple absorbance tests have shown that LepA has a similar growth curve. Once
diluted, cell growth has an even longer lag phase and does not exhibit the same level of growth. This proves that LepA does not have a toxic effect on cells when over expressed, but does show to effect growth negatively.
Today a popular method used by pharmacist to create medication is synthesis. The type of synthesis used in this research was High Pressure Liquid Chromatography. The HPLC was used to amplify hydrazones, in role of the dynamic combinatorial libraries. In using Le Chatelier’s Chemical Equilibrium Formula, the effect of trifluoracetic acid on the formation of hydrazones was studied. Polymers were altered by the trifluoracetic acid to find different ingredients that may be useful for different medications.
Le Chatelier’s Chemical Equilibrium Formula was the base of the research conducted. Adenosine, Cytidine, Guanosine, and Uridine were used as templates to effect the amplification of the hydrazones. Concentrations of the solutions
were also altered to recognize change during the amplification. All amplifications were observed using the HPLC. The Molar Mass of the templates was important in deciding precise measurements because the solubility of the hydrazones was an important factor in making amplifications.
Based on the Mass Spectrometry data of an untemplated library there is the formation of cyclic dimers, cyclic trimers, and high cyclic oligomers. The addition of adenosine as a template caused the amplification of specific library members. The addition of cytidine as a template also showed the similar amplification in the library.
These results indicate the successful formation of a dynamic combinatorial library through the reversible hydrazone formation induced by trifluoracetic acid. The effect of template additions displayed Le Chatelier’s Principle was applied to this library, giving amplification of specific library members.
Student Projects
17
Cocaine blocks the reuptake of dopamine and can alter its concentration. Determining dopamine concentration through firing frequencies is important before and after administration of cocaine. The purpose of this research is to determine if the level of dopamine concentration relates to firing frequencies of dopamine neurons. Also, knowing if cocaine administration relates to the concentration of dopamine neurons is vital.
In order to initiate experimentation it was important to fabricate carbon-fiber microelectrodes and perform stereotaxic surgery on male Sprague-
Dawley rats. After this was completed, the working electrode was able to help determine the concentration of dopamine before and after cocaine administration.
Due to the correct position of the carbon fiber microelectrode based on bregma, there was a positive connection with dopamine. Also the two stimulation frequencies tonic (high) and phasic(low), were directly proportional to the concentration of dopamine . Therefore, the higher stimulation frequency promoted more dopamine neurons.
The concentration of cocaine (1mg/kg) was not high enough to change the extracellular concentration of dopamine. Therefore, the dosage of cocaine needed to be increased because there was no apparent behavioral or neurochemical reaction.
Based on the data, the higher stimulation frequency (60hz, 40p) promoted a greater concentration of dopamine than the lower stimulation frequency (10hz, 40p). The effect of cocaine on dopamine could not be properly observed because there was no apparent reaction within the rat.
Shara K. WeaverThe Effect of Neural Firing Frequencies and Cocaine
on Dopamine Concentrations in the Nucleus AccumbensSupervisor: Dr. R. Mark Wightman, University of North Carolina
at Chapel Hill, Department of Chemistry
Melanie WileyThe Effects of Reaction Conditions on Alexa Fluor Labeling of
α-SynucleinSupervisor: Gary Pielak, University of North Carolina at Chapel Hill,
Department of Chemistry
α-Synuclein is the main protein involved in Parkinson’s disease, characterized by neuron loss in the region of the brain which controls movement, the substantia nigra. In Parkinson’s disease, α-synuclein aggregates to form Lewy bodies in the degenerating neurons. Previous studies show that oxidative aggregation of α-synuclein in vitro can mimic in vivo aggregation. These studies were done using Coomassie or antibody staining techniques which only detect small α-synuclein aggregates. The goal of this project is to see if binding Alexa Fluor dye to α-synuclein at different positions will affect the protein’s oxidative aggregation. The most effective labeling conditions also need to be found.
Results showed that for fully reduced α-synuclein, extending the binding time from 1 hour to overnight did not improve the percent of α-synuclein labeled, and in one case actually decreased the percentage labeled. Adding guanadidium hydrochloride to α-synuclein which is not fully reduced did not increase the percentage of α-synuclein labeled. Previous researched concluded that binding Alexa Flour at amino acid position 3 allows for detection of high-molecular weight aggregates at a low population. When Alexa Flour is bound at amino acid position 66, high-molecular weight aggregates are still detected at a low population. These experimental conditions will allow for a better understanding of α-synuclein oxidative aggregation so that further research can proceed to find the mechanism of Parkinson’s disease.
Student Projects
18
Melony OchiengThe Heat of Formation of Iodoethylene Studied by Threshold Photoelectron Photoion Coincidence SpectroscopySupervisor: Dr. Tomas Baer, University of North Carolina at Chapel Hill, Department of Chemistry
Rachel S. CostinEnhancing Separation of Pseudoephedrine Enantiomers Using Reverse Phase Liquid ChromatographySupervisor: Dr. J.W. Jorgenson, University of North Carolina at Chapel Hill, Department of Chemistry
The purpose of the project was to determine the heat of formation of iodoethylene using threshold photoelectron photoion coincidence spectroscopy. Based on heats of formation patterns in the alkyl halides compounds I hypothesize that the heat of formation of iodoethylene should be 124.7 kJ/mol and the C-I bond energy can be calculated to be 277.4 kJ/mol. The iodoethylene was ionized by the incident light from an H2 discharge lamp dispersed by 1-meter Monochromator. The electrons were velocity focused according to their perpendicular velocity component to the mass spectrometer. The zero kinetic energy electrons were detected in the center channeltron and collecting a second off-center channeltron compensated for the hot
electrons contamination in the center channeltron. Electrons provide the start signal for the time of flight analysis while the ions provide the stop signal. The E0 (appearance energy of the daughter) was determined from the breakdown diagram.
Using the below equation the heat of formation at zero Kelvin was determined. DfHo (C2H3I) = -AE + DfHo (I) + DfHo (C2 H+DfHo (C2H3I) = - 1087.9 kJ/mol + 107.24 kJ/mol + 1119.6 kJ/mol = 138.9 kJ/mol
To change the heat of formation form 0 K to 298 K I calculated the thermal energy of iodoethylne at 298 using this equation.
The heat of formation of iodoetheylene is 129.8 kJ/mol at 298 Kelvin. And the C-I bond energy is 267.7 kJ/mol. The results are consistent with my hypothesis; if the approximate calculations are correct then the measured heat of formation of iodoethylene should be 120kJ/mol and the C-I bond energy of iodoethylene can be calculated. The hypothesis is supported because the heat of formation was determined to be 129.8 kJ/mol at 298 Kelvin. It also is supported by Cao et al estimation. He estimated that the heat of formation of iodotheylene should be 128.1 kJ/mol at 298 Kelvin.
The study of enantiomertic separation is of increasing importance in the pharmaceutical industry. In this work the enhancement of enantiomeric separation of pseudoephedrine (PSE) and ephedrine has been studied using Reverse Phase Liquid Chromatography (RPLC). Running conditions of the experiment have been altered to measure improvements of analyte resolution. Experimental conditions were modified by changing: mobile phase composition (percent organic to non-organic solvent), type and concentration of cyclodextrin additives, and temperature. The enatiomers that were tested are as follows: (1R, 2R)-(+) pseudoephedrine, (1S, 2S)-(-)
pseudoephedrine, and (1R, 2S)-(-) ephedrine. Both □-cyclodextrin (B-CD)and Carboxymethyl-□-cyclodextrin (CM-B-CD) were investigated as chiral mobile phase additives to improve resolution. Changes in resolution and enantioselectivity were evaluated. It was concluded from this study that the best resolution between enantiomers was seen with CM-B-CD at ambient temperature.
Student Projects
19
Arthur G. Affleck IVSilencing the ATP Dependent Potassium Channel in Pancreatic
Beta CellsSupervisor: Dr. Christopher Newgard, Duke University, Sarah W. Stedman Nutrition and Metabolism Center
ATP-dependent Potassium Channels (KATP) are present in many tissues, including heart, skeletal muscle, vascular muscle, brain, and the beta cells of the pancreatic islets. Their function in the beta cells is to regulate the secretion of insulin into the blood as a response to a rise in blood glucose after the ingestion of food. An increase in the ATP/ADP ratio in the beta cells after a rise in blood glucose closes the channels and this leads to insulin secretion. This process is known as glucose stimulated insulin secretion(GSIS). Previous studies from the Newgard Laboratory have demonstrated that even in the background of a high ATP/ADP
ratio, GSIS from the beta cell was decreased. This suggests that there may be a secondary mechanism of GSIS in pancreatic beta cells. Our research is geared to directly test the KATP channel’s effect on GSIS by using siRNAs complimentary to the channel in gene knockdown experiments. Expression of the ATP-driven potassium channel was suppressed by introducing siRNA duplexes complementary to mRNA sequences of the sur1 and kir 6.2 subunits of the potassium channel. GSIS was inhibited with the knock down of the kir 6.2 subunit of the KATP channel. Knockdown of the Sur 1 subunit was unsuccessful.
Andy T. SmithDetermining the Thermal Stability of DNA Nanogrid: Effects of
Nicking and U Strand Stabiizing HybridsSupervisor: Thomas H. LaBean, Duke University,
Department of Chemistry
Artificially designed DNA complexes show promise as building blocks for the construction of useful nanoscale structures, devices, and computers. However, to use nanogrid in large scale production processes requires an understanding of the factors that affect the stability of the structures. The thermal stability of these lattices is important fundamental knowledge that could be one of the many factors controlling their behavior, and ultimately, their widespread application in manufacturing processes. Furthermore, not only knowing, but increasing the thermal stability of DNA nanogrid using oligonucleotide-peptide conjugates effectively increases the DNA workspace, facilitates a larger range of unique sequences used in nanogrids, and enables greater flexibility for nanostructure design. Using DNA nanogrid with one solid core strand as a control, we prepared DNA nanogrid with nicked core strands in all the tiles, and prepared a second experiment with
stabilizing U Strand conjugates to the core strand of each tile. Nucleotide sequence design for the synthetic strands was assisted by the application of algorithms that minimize possible alternative base-pairing structures. The nanogrid samples were slowly cooled from 95oC to 4oC over a period of 16 hours. Melting was performed with 200µL of pre-annealed DNA lattice at 0.10µM using a Cary UV-Vis spectrometer. 200µL of 1X TAE/Mg2+ buffer was used as a control. The temperature of the lattice was increased from 25oC to 90oC at 0.2oC/min, before being cooled to 25oC again at the same rate. Derivatives of the melting curves were calculated using Microsoft Excel. We observed an increase in the 1 pc core nanogrid melting temperature of approximately 1°C, from Tm = 62±1°C to Tm = 63±1°C, and an increase in the 2 pc core nanogrid melting temperature of approximately 2°C, from Tm = 56±1°C to Tm = 658±1°C.
We have successfully demonstrated a marked increase in the thermal stability of a complex DNA nanostructure via the incorporation of connected U Strands. Analysis of these and other published data suggests that U Strands generally have a clear stabilizing effect on short-chain DNA-U Strand conjugates. Future implicates of DNA-U Strand conjugates include the construction of larger structures form multiple DNA-U Strand units, and DNA-based computation.
Read about Andy's experience in Denmark on page.........
Student Projects
20
Catherine PeeblesNew Ways to Improve MRI Using Intermolecular Multiple Quantum Coherences Applied to Chelonia Mydas and Panulirus argusSupervisor: Dr. Warren S. Warren, Duke University,Department of Chemistry
Danielle BlackInvestigating the Effects of Mechanical Strain on the Regioselectivity of Rhodium Catalyzed Hydroformylation Using an Elastomeric SupportSupervisor: Dr. Stephen Craig, Duke University,Department of Chemistry
Every year, Chelonia mydas (sea turtles) and Panulirus argus (spiny lobsters), both migrate across vast expanses of ocean to arrive at specific nesting areas and feeding sites. Scientists hypothesize that they use two techniques to navigate (define techniques? AC5). The hypothesis that we are testing is do sea turtles and lobsters have magnetic particles in their brain that helps them navigate. In our research, the method used was magnetic resonance imaging with intermolecular multiple quantum coherences. Based on prior research and various articles (insert references? AC6), Chelonia mydas and Panulirus argus interact with the external magnetic field of the earth. The
intermolecular multiple quantum coherences were inconclusive in detecting magnetic particles in Panulirus argus. The salt content in the lobsters prevented us from getting good matching in the coil and it altered the relaxation time. In the future, we will try to decrease the salt content in our sample by storing it in fresh water instead of natural salt water. When the images show anisotropy then scientists will be able to see what specific particles help the Chelonia mydas in its navigation.
It has been previously established that a rhodium/phosphine complex is a catalyst when not attached to a polymer. We hypothesized that the complex is also a catalyst when attached to a polymer. Based on this hypothesis and other information, we devised an experiment to create the first mechanocatalyst.
In the experiment, a comparison of the aldehyde products from the hydroformylation of gels that have undergone the mechanical strain of stretching are compared to gels that have not undergone any mechanical strain. All of these gels contain a rhodium (I)/phosphine complex. The idea of this experiment is that by adding mechanical strain to the gels, the ratio of linear and branched aldehyde products will change and a mechanocatalyst can be created to favor one particular product.
At this time, the experiment is still on going and the results are currently inconclusive. If the results are as expected, they can be used commercially to improve the process of creating carboxylic acids, alcohols, and other products, and to produce other mechanocatalysts.
Student Projects
21
Shaun R. FultonThe Biophysical Analysis of Proteins in Complex Mixtures;
Experimentation with SPROXSupervisor: Dr. Michael Fitzgerald, Duke University,
Department of Chemistry
SPROX (the stability of proteins at rates of H/D exchange) was performed on ubiquitin, trypsin, cytochrome c, lysozyme, myoglobin, and lactalbumin. The results analysis of the proteins after SPROX was performed were compared to SUPREX C1/2 values and other techniques such as circular dichroism (CD) and fluorescence that are used to calculate the mass-to-charge ratios of proteins. SPROX was used on a protein that
contained the amino acid methionine. 1.67µL of hydrogen peroxide was added to the protein/buffer solution to oxidize the methionine. The reaction was then quenched with 1.67µL of bovine catalase. The protein was the desalted using C18 ZipTips. The protein was then analyzed using the ESI (electrospray ionizer).
Kirsten. N. BazemoreCharacterization of Second Coordination Shell
Host-Guest Interaction by Electrospray Ionization Mass Spectrometry
Supervisor: Dr. A. L. Crumbliss, Duke University,Department of Chemistry
Purpose: Host-guest complex is the formation of two or more molecules or atoms that form a distinct structural relationship. The host-guest complex consists of two units which are the host and the guest. Host-guest complexes are important because they model biological systems. We are interested in bacterial iron transport. In this case, the host is a receptor and the guest is Ferrioxamine B. Ferrioxamine B is the siderophore that transports iron across the cell membrane of some bacteria. This system can be modeled using 18-Crown-6 and potassium. In recent studies, equilibrium constants were calculated for the host-guest system of this crown-ether and potassium chloride. A calibration curve for this system was created. Presented here is the examination of the 18-Crown-6 and potassium host-guest complex with the presence of a standard
using ESI-MS. We hope to produce a reproducible method for investigating host-guest complexes using ESI-MS.
Methods: Ultra Violet-Visible Spectroscopy was used to understand the characteristics of Ferrioxamine B. This technique was also used to make sure pipetting skills were accurate. Electrospray Ionization Mass Spectrometry was used to monitor the interactions between the host and guest in the presence of a standard.
Results: The UV-Vis results showed the pipetting skills were accurate. Tetra-N-butyl ammonium acetate and tributylamine were used as standards in ESI-MS experiments. Between each sample, the intensity of the standard changed. The intensity of host-guest complex increased and then became saturated as we increased the concentration of the host.
Conclusions: The stability of the standard was not optimal. However, the association constant of the host-guest complex matched the reported values in the literature. Since the host-guest complex behaved as expected, it has been proven that ESI-MS shows promise in monitoring host guest complexes.
Student Projects
22
Rakeem ChesneyZeolite and Poly (Ethylene Glycol) Polymers interaction using Atomic Force microscopy based Dynamic Force SpectroscopySupervisior: Dr. Boris Akhremitchev, Duke University,Department of Chemistry
Charles RamseyFinding Ligands of B2AR that Enhance Decoupling of Signaling Pathways Using Computational MethodsSupervisor: Dr. David Beratan, Duke University,Department of Chemistry
Zeolites are microporous disordered solids with significance in many industrial processes because they can hold, release, absorb, and exchange different chemicals, nutrients, toxins, ions, or polymers according to need. The equilibrium properties of flexible polymers confined within these materials plays an important role in a variety of applications, but the details of zeolite-absorbate interactions are not well understood. A detailed characterization of the polymer molecular binding process is necessary for a complete understanding of how zeolites mediate chemical processes. Experimentally this characterization has proven difficult because the molecular binding
processes could not be directly measured. Recently developed atomic force microscope (AFM) based single molecule force spectroscopy will be used to overcome these experimental difficulties. Force spectroscopy will allow for the direct analysis of unbinding forces measured as individual bound polymer chains separate from zeolite crystals quantifying the kinetic and thermodynamic parameters of these intermolecular interactions not available using other techniques. These parameters will allow for the elucidation of the chemical nature zeolite-polymer binding interactions and enable the further development of the many applications of zeolites.
G-Protein Coupled receptors (GPCRs), also called 7 Trans-membrane Receptors (7TM), represent by far the largest, and most versatile of the seven families of plasma membrane receptors and membrane proteins encoded in the human genome. GPCRs are being targeted by between a third and a half of the worlds marketed drugs. B2AR (□2 Adrenergic receptor) type GPCR can activate, simultaneously, more than one pathway, and the signaling can be decoupled. All current drugs that target B2AR activate two pathways which can lead to a number of unwanted side effects. The purpose of this research is to differentiate between the pathways of cyclic adenosine monophosphate (cAMP) and □-arrestin.
Here, we will address this issue using computational chemistry methods to study the properties of different ligands and how they influence the differentiation of pathways.
It is hoped that by differentiation of the cAMP and □-arrestin pathways of B2AR, better drugs with fewer less severe side effects will be produced and a better understanding of how small molecules elicit a cell response, known as signaling will be gained.
Student Projects
23
Michael A. SanchezProbing Binding and Structural Properties
of a Novel Ubiquitin-Binding DomainSupervisor: Dr. Pei Zhou and the Zhou Research Group,
Duke University, Department of Biochemistry
Ubiquitin is a highly conserved 76 amino acid protein that is involved in the regulation of numerous biological processes, including DNA repair. The ubiquitin-binding motifs (UBM), found within the C-termini of the human DNA Y-family polymerase ι, are important in the recruitment of this specialized polymerase to monoubiquitinated PCNA at the damaged replication site. The purpose of this research was to overexpress, isolate, and purify the wild-type and mutant constructs of the UBM2 domain of human polymerase ι, in addition to their binding partner, ubiquitin for biophysical characterization. This provided large quantities of soluble purified protein that was used in binding measurements using Isothermal Titration
Calorimetry (ITC). ITC revealed a binding affinity (Kd) of 20 uM for the wild-type ubiquitin-binding motif for wild-type ubiquitin. Mutation F688A, phenylalanine to alanine, abolished the binding of UBM2 to ubiquitin and mutations P692A and L699A decreased the affinity by ~3 fold. These results highlight the importance of these residues in the formation of the ubiquitin-UBM interface involved within the recruitment of specialized polymerases for DNA repair and Translesion synthesis.
Ursala N. LocklearAdditivity in Ligand Binding
Supervisor: of Dr. Eric J. Toone, Duke University,Department of Chemistry
Matrix metalloproteinases (MMPs) play an important role in myriad pathological processes including cancer, rheumatoid arthritis, coronary artery disease and emphysema. Previous efforts to develop therapeutic inhibitors have been severely hampered by a lack of inhibitor specificity, which led to significant cross-inhibition and toxicity. Thus, these investigations aim to understand the thermodynamic basis of affinity for MMPs – particularly how additivity drives ligand binding. This knowledge could then be applied to the design and development of specific MMP inhibitors. MMP-3 (stromelysin-1) will be used as a model system for these studies. Recombinant MMP-3 was expressed using previously described conditions. All inhibitors were synthesized according to previously described methodologies. Isothermal
titration calorimetry was conducted to measure the thermodynamics of binding of all linkage ligands and their constitutive fragments.
ΔG, ΔH, TΔS, ΔCP, and proton transfer events were determined for all ligands in the series. An additivity analysis revealed that additivity was enthalpically driven for the linkage ligand binding only two subpockets. Linkage ligands binding three subpockets all entropic and enthalpic benefits of chemically tethering two constitutive fragments. For the most complex linkage ligand binding four conceptual pockets within the active site, additivity was driven solely by entropy. These experiments support previous observations that, at its simplest, additivity is an enthalpically driven phenomenon rationalized by the interfacial mobility model. Chemically tethering two conceptual fragments causes the protein to contract around the ligand,
thereby maximizing electrostatic and hydrophobic interactions. This contraction also results in an entropic penalty, possibly due to freezing numerous vibrational modes. As the linkage ligand becomes more complex, the entropic penalty of adopting a rigid body conformation outweighs the enthalpically benefit of any new interaction. Thus, the protein relaxes, and additivity becomes entropic in nature.
Student Projects
24
Staff and Program Management
Pictured left to right: Donald Guth, Micheal Cherry, Ken Cutler, John Greene, Deborah Rogers, Gwendolyn Taylor, Faye McNeal, Tyjunna LaBennett, and Josie Cutler.
Principal InvestigatorsPrincipal Investigators (PIs) are
essential to the success of this
program. This program has been
fortunate enough to secure and retain
many of the best research scientists
in the country, definitely among the
best in the State of North Carolina.
The best preceptors provide the best
research educational experiences
for the students, therefore take our
students from disadvantaged to a
truly educationally and experientially
advantaged status.
Responsibilities:
• Approve and provide student
access to their research facilities,
instrumentation, and materials
• Along with members of their research
teams, provide our students with the
science methodology necessary to
conduct a research investigation
• Provide invaluable input on
enrichment activities and program
improvements.
• Provide training to the staff on their
area of expertise
• Serve as guest lecturers for SEED
Seminar to provide expertise on
career options, ethics and their
scientific discipline
• And in some cases, provide extended
opportunities for student to work
in their labs during their collegiate
years, during the year and/or
summers
2007 Principal Investigators
Duke University
Dr. Eric Toone, Anne T. and Robert M. Bass, Associate Professor of Chemistry and Associate Professor of Biochemistry,
Dr. Chrs Newgard, Sarah W. Stedman, Nutrition and Metabolism Center at Duke University
Dr. Thomas LaBean, Assistant Professor, Dept. of Chemistry
Dr. Warren Warren, Professor and Chair, Dept. of Chemistry
Dr. Stephen Craig, Professor, Dept. of Chemistry
Dr. Micheal Fitzgerald, Professor, Dept. of Chemistry
Dr. Boris Akhremitchev, Asst. Professor, Dept of Chemistry
Dr. Alvin Crumbliss, Professor and Dean of Natural Sciences
Dr. David Beratan, Professor, Dept. of Chemistry
Dr. Ann Lazaraides Professor, School of Engineering
NC State University
Dr. Dennis Brown, Professor of Biochemistry, Chair, Dept. of Biochemistry
Dr. Raquel Hernandez, Professor of Biochemistry
Dr. Edward Sisler, Dept. of Biochemistry
Dr. Allan Foegeding, Professor, Dept. of Food Science
Dr. Marc Cubeta, Professor, Dept. of Plant Pathology
Dr. Melissa Pasquenelli, Assistant Professor, Dept of Textiles, Chemistry, and Science
Dr. Russell Gorga, Asst. Professor, Dept. of Textiles, Chemistry, and Science
University of North Carolina at Chapel Hill
Dr. Gary Pielak, Professor, Dept. of Chemistry
Dr. Louise M. Ball, Professor, Dept. of Environmental Enginerring
Dr. Marcey Waters, Assistant Professor, Dept. of Chemistry
Dr. J. Papanikolas, Asst. Professor, Dept of Chemistry
Dr. Garegin Papoian, Asst. Professor, Dept. of Chemistry
Dr. Linda Spremulli, Professor, Dept. of Chemistry
Dr. Micheal Gagne’, Professor, Dept. of Chemistry
Dr. R. Mark Wightman, Assistant Professor, Dept. of Chemistry
Dr. Thomas Baer, Assistant Professor, Dept. of Chemistry
Dr. J.W. Jorgenson, Professor, Dept. of Chemistry
The NC Project SEED StaffKenneth A. Cutler, DirectorJohn Greene, Assistant Director, Interim Site Coordinator NC State UniversityGwendolyn Taylor, Assistant Coordinator- Duke UniversityTyjunna LaBennett, Assistant Coordinator- NC State
Micheal Cherry,Assistant Coordinator- UNC-Chapel HillFaye McNeal, Scholarship CoordinatorJosie B. Cutler, Activities Coordinator
Deborah Rogers, Science Fairs Coordinator
Donald Guth, Administrative Assistant
25
This past summer (July 29 to August
10, 2007), I traveled to Arhus,
Denmark to conduct research with
a team of five other Duke students.
I conducted research under the
supervision of Dr. Thomas LaBean
in the Duke University departments
of Chemistry and Computer Science.
Traveling with us were Dr. Josh Carter
who is a postdoc for Professor
LaBean, Elizabeth Irish who is a 4th
year Mechanical Engineering and
Materials Science graduate student
at Duke, Kristine Obusek who is a 1st
year graduate student in Biomedical
Engineering at Duke, and Patrick
Videau who is a Goucher College
student with a Biological Sciences
major with a focus in Molecular
Biology.
While in Denmark, I studied
the thermal stability of DNA
nanostructures under a variety of
solution conditions. In doing this
research, I had the opportunity to work
with many Danish Professors and
students including Dr. Kurt Gothelf,
Jørgen Kjems, and Wael Mamdouh.
NC Project SEED InternationalAndy SmithInternational Research Experience in Science (IRES): Denmark
The Danish experience was truly
amazing from the scientific and
intellectual merit of the experience
all the way to the food and cultural
aspects of the visit. We immersed
deeply into Danish culture by renting
bikes to tour the town, visiting the
Aros Art Museum, visiting Den Gambly
By Musem, and even taking part in a
canoe excursion near Silkeborg with
Danish students.
Starting August, we began to work in
the labs. The labs at Aarhus University
took some adjustment because
everything was in Danish, of course.
However, in no time, I fell right into the
swing of things. I particularly enjoyed
preparing microscopic solutions with
exact stoichiometry. The lab was very
intense abroad. We went into the lab
as early as 7:00 am on some days
until about 11:30 pm on some nights.
I really enjoyed this experience and
wouldn’t trade it for anything. It’s
nothing like taking the skills you’ve
learned in one place and applying them
to different situations. The atomic
for microscopes (AFMs) and UV/Vis
Spectrophotometers weren’t the same
as those at Duke. Due to this, I had to
apply the knowledge that I knew about
these machines and my project to
make things happen.
In the end, it was a great experience,
and the trip had the perfect mix
of cultural exploration with a lot of
science. I can’t wait to return to
Denmark this upcoming summer to
continue working with these amazing
professors.
Before the end of my
experience, we capped
things off with a mini-
symposium of everyone’s
projects. I was the only
presenter that didn’t have
at least a four-year degree
as well as the only minority
presenter. This was a huge
accomplishment for me.
25
26
NC Project SEED InternationalMelanie Wiley and Brandon Young The North Carolina International Science Challenge (NCISC)
The North Carolina International
Science Challenge (NCISC) is a yearly,
North Carolina science competition,
offered by the Grassroots Science
Museums Collaborative that chooses
several excellent inquiry-based science
projects to display at the Beijing
Youth Science Creation Competition
(BYSCC), held during the third week
of March 2008 in Beijing, China. The
NCISC is open to middle and high
school students in North Carolina.
Students are sponsored by staff at any
of the Grassroots Science Museums
Collaborative (GSMC) institutions.
The BYSCC is an exiting experience
along with the breathtaking cultural
events, such as visiting the Great Wall
of China. The Beijing Association of
Science and Technology (BAST) is
host to our delegation consisting of
students and adults. The students
chosen through the NCISC process
are the sole representatives of the
United States of America. The BYSCC
features students from many counties:
therefore this is an unparalleled
opportunity for students to interact
with future scientists from around
the globe. This year two of the four
students selected to participate were
NC Project SEED students Melanie
Wiley and Brandon Young. Melanie
Ochieng was selected as the first
alternate.
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NC Project SEED AlumniKenneth Gibbs, Jr.Ph.D. Student, Immunology Program, Stanford School of Medicine
September 26, 2005
Kenneth Gibbs, Jr., is one of 7 incoming students to choose the immunology home program as his point of departure. Growing up in Durham, N.C., Gibbs attended the University of Maryland-Baltimore County and graduated with a BS in biochemistry and molecular biology.
Why are you drawn to science and research? Even though the process of discovery can be very frustrating at times, the feeling you get looking back over several months of work and seeing that you have contributed something new to the greater body of knowledge is very rewarding. You have to have doctors to treat people but they aren’t much use if they don’t understand the mechanisms behind disease and if they can’t give any drugs to help. So that is where research comes in. You have to complete the cycle.
Why did you come to Stanford?I first came to Stanford for the Summer Research Program the summer after my freshman year and I fell in love with the place. I had never been to California before. Coming from North Carolina, a summer without heat, humidity and bugs was such a novel concept to me. I worked with Yvonne Maldonado, a population-based epidemiologist, on a retrospective study looking at trends in the treatment of HIV-infected mothers and how they
correlated to mother-to-child transmission. When I applied for graduate school and came back, I fell in love all over again. The environment seems to empower students. You get the feeling that people really want you here and see you as a contributing member of the community.
Ticora Johnes, Ph.D.Plolymer Science and Engineering, University of Massachusetts—Amherst
Profile from FOCUS, Winter 2007
Measuring the success of an informal science educational program is a difficult task. The variables that allow one student to excel and another to just get by are too numerous and impossible to quantify into some ubiquitous formula for success.
As a high school student at the North Carolina School of Science and Mathematics, Ticora Jones was involved with the NC Project SEED chapter, a program sponsored by the American Chemical Society to encourage minority and disadvantaged students to pursue science. She recently completed her Ph.D. in polymer science and engineering at the University of Massachusetts—Amherst. Without NC Project SEED she said that she would not have considered a career in science.
Dr. Jones signed on for NC Project SEED and was placed in Dr. Eric J. Toone’s chemistry laboratory at Duke University. This was the fit she was looking for, and she returned the following summer and during her senior year.
The introduction to the chemistry laboratory was a defining moment for Dr. Jones. Not only did it solidify her decision to pursue a career in science, it also provided her with the opportunity to display and discuss posters of the lab group’s work at the American Chemical Society’s meeting in Chicago.
After high school, Dr. Jones attended the Massachusetts Institute of Technology where she majored in Materials Science & Engineering. She received a Martin Luther King Jr. Leadership Award in 2000 for her numerous involvements and leadership in campus activities, including being one of the founders of MIT’s Black Women’s Alliance.
At a family reception recognizing Dr. Jones’ achievement, NC Project SEED offered its own congratulatory honor by announcing the creation of the Ticora Jones Trailblazer Award to acknowledge students from Project SEED (the expanded statewide program) who receive their doctorates.
“We wanted to celebrate Dr. Jones’ accomplishment and to provide incentives for other students in our program,” said Kenneth Cutler, director of NC Project SEED. “We also wanted to reiterate that the mission of our program is for the students to obtain professional and terminal degrees and not just to get a job in science.”
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February 12, 2008
When Thomas Freeman arrived in the
lab of William Wimley in the Tulane
School of Medicine, he propelled
the lab into a new era of research.
In recognition of his work, Freeman
received a Minority Travel Award from
the Biophysical Society to travel
to Long Beach, Calif., for the joint
meeting of the Biophysical Society and
the International Biophysics Congress.
Freeman, who is working toward a
PhD in biochemistry in the biomedical
sciences graduate program in the
School of Medicine, was selected for
the award for his research on proteins
of disease-causing bacteria. He was
able to attend the world’s largest
meeting of biophysicists with a Minority
Travel Award from the Biophysical
Society.
He is one of four graduate students
working in Wimley’s lab, which has
more than $1 million in funding from
the National Institutes of Health over
four years. Wimley, an associate
professor of biochemistry, says
Freeman was instrumental in securing
the grant renewal that the lab received
after Hurricane Katrina.
“He is responsible for taking my lab
into an entirely different realm,” Wimley
says. “Our work has focused on a
model system of synthetic membranes
to study proteins on the surface of
cells. Now we can take our work to the
next step using living organisms, rather
than other labs pursuing that work
based on our model system studies.”
NC Project SEED AlumniThomas FreemanPh.D. Student, Biochemistry, Tulane School of Medicine
According to Freeman, “We are
developing a technology to find the
genes related to proteins that are
present on the surface of certain
types of disease-causing bacteria.
This technology will someday be used
to expedite the development of new
vaccines or drug therapies against
these bacteria.”
Freeman says that he also is interested
in disparities in public education based
on regional socioeconomic status, and
hopes to one day found a science and
technology academy for underprivileged
children.
“My desire to give this opportunity to
the community is inspired by a number
of extraordinary people who gave me
opportunities that shaped who and
what I am today,” says Freeman, a
graduate of Xavier University in New
Orleans. “I’ve experienced most of the
situations that urban youth face, and
in spite of those things I managed to
succeed because of my strong mother
and several teachers who saw in me
something remarkable. I hope to repay
their investment in me with interest.”
Former NC Project SEED Students Admitted to Graduate/Doctoral Programs
SEED Alumnus Graduate/Professional School Discipline
Kizzmekia Corbett Johns Hopkins Immunology
Jacqueline Ellis UNC-Chapel Hill Genetics
Thomas Freeman Tulane Biochemistry
Amber Gaither Meharry Medical College Medicine Gates Millenium Scholar
Kenneth Gibbs Stanford Medical School Immunology
Marcus Hill, M.S. Yale University Public Health Gates Millenium Scholar
Ticora Jones, Ph.D. University of Massachusetts Materials Science
Faith Ohuba Boston University Medicine
Edward Perry, M.S. UNC-Chapel Hill Chemistry
Douglas Sanford Meharry Medical College Dentistry
Devin Sanders Medical College of Virginia Pharmacology
Emil Thompson NC State University Bioinformatics
Tiffany Williams Stanford Medical School Cancer Biology
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Scholarship CoordinatorThe addition of Ms. Faye McNeal, as
the program Scholarship Coordinator,
greatly enhanced our program. With
recruitment, Ms. McNeal efforts
resulted in a dramatic increase of high
caliber student applicants statewide
by using her counseling expertise
and contacts at the high schools.
Her efforts were so effective that
a high number of highly qualified
applicants were turned away. With
Student Scholarships Ms. McNeal
efforts produced over $2,800,000
in scholarships for 15 of our senior
students.
Recruitment of Principal Investigators and ScientistsDepartment Chairs of Chemistry at
Duke and UNC, and the Chair of the
Structural and Molecular Biochemistry,
invited us to do a 15 minute
presentation at their monthly faculty
meetings. As a result we had more
PI/mentors to volunteer than we had
students to place. Our students must
also maintain communications with
their PI/mentors throughout the year.
Reflections on 2007
Student Stipend IncreaseAfter the acquisition of the Burroughs
Wellcome Fund grant, the National
American Chemical Society‘s NC
Project SEED program increased
the amount of the student stipends
for SEED I students from $2275 to
$2500, and SEED II students from
$2500 to $3000. Unfortunately, this
increase was not reflected in the
budget and we had to raise the money
or decrease the number of students.
The NC Local Section of the American
Chemical Society provided the
additional funding under the condition
that for the remainder of the grant
the program would raise the funds
or decrease the number of students
served. It is our intent to raise the
funds and not decrease the number of
students.
Exit Interviews/EvaluationThe Director and Assistant Director can
provide valuable insights for program
improvements through brief exit
interviews during the month of August,
in addition to our written evaluations.
Duke Youth Programs (DYS)A model program that assisted with our
residential component. DYS provided
outstanding Residential facilities (Bell
Tower), residential counselors, student
activities, and eased the transition for
campus residential life.
Student ApplicationsNext year we plan to have an earlier
application deadline so that we may
conduct interviews, make selections
earlier, and therefore notify students
earlier of their acceptance in the
program.
Intel International Science and Engineering Fair (Intel ISEF) Science FairWe can now affiliate with the ISEF and
have a fair among the students in the
NC Project SEED program. This will be
considerably less time consuming.
SEED Academy for Leadership Training and Science (SALTS) AttendanceWe plan to extend the pay period of
students from June to January to
encourage better attendance at SEED
Academy.
The 2007 (17th ) edition and expansion of NC Project SEED was highly successful with our inaugural administration of a statewide residential program. The following highlights and concerns were presented:
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Direct Cost
I. Personnel
Salaries Project Director $30,000 Secretary $25,000 Coordinators $48,000 Residental Counselors $6,000
Consultant and Contract Services Field Trips $5,000 Program Evaluation $4,000
II. Non-Personnel SAT Preparation Course $11,250 Materials and Supplies $5,000 Web Site Design and Maintenance $1,000 Institutional Expenses $7,500 Duke Youth Residential Program $26,000 Student Stipends $25,713
Totals $194,463
Indirect Cost ACS Matching Funds (SEED Student Stipends) $30,713 The Hamner Institutes for Health Sciences (In-Kind) $25,000
Budget — Year 1November 15, 2006 — November 15, 2007
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For more Information or to apply online go to:www.ncprojectseed.org
Kenneth Cutler, DirectorNC Project SEED
The Hamner Institutes for Health SciencesPO Box 12137 • 6 Davis Drive
Research Triangle Park, NC 27709-2137
Sponsored by Burroughs Welcome Fund
North Carolina Section of the American Chemical SocietyThe Hamner Institutes for Health Sciences