Provost's Undergraduate Research Mentoring Program
Project Descriptions, Summer 2008

Sheryl Beck

Anxiogenic effects of chronic estrogen exposure in female mice

Gonadal hormones, such as estrogen, modulate mood in humans and animals and have been implicated in fluctuations of mood across the female reproductive cycle. In addition, the lifetime prevalence of depression in women is twice that of men. However, the majority of studies examining the biological mechanisms underlying stress/anxiety/depression have utilized animal models consisting solely of males. The proposed research examines the effect of chronic estrogen on stress/anxiety/depression in female mice. The effect of estrogen is mediated by at least two estrogen receptor subtypes: ER-a and ER-b. Expression of ER-a and ER-b varies by brain region and in response to the hormonal status of the animal. In general, these two receptor subtypes have opposing effects with ER-b activation decreasing behavioral indices of anxiety and ER-a activation increasing anxiety. Recent work in our lab has shown that chronic estrogen treatment increases anxiety as measured in the Open Field test whereas previous labs have shown that acute estrogen administration decreases anxiety in this behavioral test. This suggests that chronic estrogen exposure may preferentially activate ER-a whereas acute administration targets ER-b. The current project will test whether long-term, chronic estrogen exposure mediates its anxiogenic effects via ER-a, ER-b, or both. The student will perform small animal surgery (ovariectomy) to remove endogenous sources of gonadal hormones, treat the animals with a combination of ER-a and ER-b antagonists and agonists, and then perform behavioral testing. Following this, the data will undergo statistical analysis.

Expression of GAD 65/67, ER-a, and ER-b in the dorsal raphe following chronic estrogen treatment

Cellular mechanisms underlying stress-induced behaviors and stress related psychiatric disorders involve the 5-hydroxytryptamine (5-HT) cell body containing nuclei of the raphe. The dorsal raphe (DR) contains a large portion of the 5-HT projecting neurons. Release of 5-HT from cell bodies in the DR is mediated in part by input from GABA-ergic neurons. Preliminary data from our lab suggests that chronic estrogen exposure increases inhibitory post-synaptic currents, which are mediated by GABA input, in the DR. The DR is composed of three subregions: lateral wing (lw), dorsomedial (dm), and ventromedial (vm). The two estrogen receptor subtypes (ER-a and ER-b) and GABA are differentially expressed across these three subregions. ER-a and GABA are more prevalent in the lateral wings whereas the ventromedial DR contains substantial numbers of ER-b neurons and very little GABA. The current project will utilize immunohistochemistry to examine expression of GAD65/67 (an enzyme within the biosynthetic pathway for GABA), ER-a, and ER-b to determine first whether these are co-localized within the same cells across the subdivisions of the DR. In addition, the project will examine whether or not chronic estrogen treatment alters the distribution and expression of GAD65/67, ER-a, and ER-b in the DR. The student will perform small animal surgery (ovariectomy) to remove endogenous sources of gonadal hormones, treat the animals with estrogen, prepare brain tissue, perform immunohistochemistry, and quantify stained cells under epifluorescence. Following this, the data will undergo statistical analysis.

Ray Roginski

My laboratory is elucidating the roles of a novel gene, GRINL1A, discovered and characterized genomically and transcriptomically in our lab, (Roginski et al., 2004, Genomics 84: 265-276). Because an important role involves glutamatergic neurotransmission, one of our primary goals is to develop a clinically useful strategy to achieve neuroprotection. Our experiments to date reveal that several GRINL1A proteins appear to associate directly with and exert a positive modulatory effect on the NMDA receptor; for this reason these Gcom proteins may be exploitable as therapeutic targets. The GRINL1A gene also may have wide-ranging effects by altering the transcription of many target genes due to the recently discovered role of the GRINL1A Gdown1 protein as the 13th subunit of RNA polymerase II (Hu et al., 2006, PNAS 103: 9506-9511). We employ molecular biology, genomics, proteomics, AAV expression, RNAi, fluorescence microscopy and other techniques. Each week the mentee will read and discuss a relevant paper from the literature. Significant contributions to the projects will result in authorship on any abstracts and papers that result from data obtained by the student. Finally, the student will be expected to present a summary of their work at the conclusion of the program.

Overexpression and knock-down of GRINL1A proteins in cultured neurons

We hypothesize that GRINL1A Gcom proteins facilitate the actions of the NMDA receptor, so overexpression should increase toxicity induced by NMDA application. Conversely, knock-down of Gcom protein expression should reduce NDMA toxicity. The first goal of this project will be to engineer a human GRINL1A Gcom1-fluorescent protein chimera in an adeno-associated virus (AAV) vector, produce infectious recombinant Gcom1-EGFP-AAV, use these viruses to infect a large percentage of the neurons in the cultures and achieve high levels of expression of the transgene therein (as measured by EGFP fluorescence) in addition to the endogenous rat Gcom proteins. We shall then quantitate NMDA toxicity in recombinant virus infected versus control cultures using the MTS assay and other means of assessing neuronal viability. Second, we shall use RNA interference to reduce expression of the endogenous rat Gcom proteins and similarly quantify neuronal viability.

Identification of human brain proteins that interact with GRINL1A proteins

In order to reveal a gene's functions it is essential to find as many proteins as possible with which the gene of interest interacts. To achieve this goal, we conducted a yeast two-hybrid (Y2H) screen of a human brain cDNA library, whose purpose was to locate interacting protein partners that associate with a specific "bait" segment of the GRINL1A Gcom1 cDNA. This screen yielded 48 positives from the ~1 x 107 clones in the library. The first goal of the project is to identify at least 10 of these clones during the allotted time. Passenger cDNAs will be isolated by PCR amplification and/or transformation of the Y2H plasmids into E. coli, followed by DNA sequencing and bioinformatic identification of the encoded reading frames. The second goal will be to select the most interesting interaction and attempt to confirm that it occurs in a mammalian system, using cultured rat neurons and rat brain tissue. Anti-GRINL1A antibodies for this purpose are already available in the PI's lab. We expect that the NMDA receptor NR1 subunit cDNA will be one of the interactors among the Y2H positives, which would provide strong evidence to confirm the results of three lines of evidence supporting this interaction already obtained in our lab. Additionally, we predict that novel, exciting interactions will be uncovered.

Lynnae Schwartz

Quantitative analysis of neural progenitors in archival pediatric brain from children HIV-infected early in life.

The neuropathological and developmental consequences of in utero or perinatal HIV-1 infection of the immature human CNS are incompletely understood. Children infected with HIV-1 after in utero or perinatal exposure to the virus may develop neurological problems (neuroAIDS), especially if their access to treatment is limited, or if they develop treatment-resistant disease. Pediatric progressive encephalopathy (PE) is a form of neuroAIDS that causes significant developmental delays, cognitive impairment and other, sometimes painful symptoms. PE can be quite devastating, yet the underlying mechanisms of HIV-1 associated PE are understudied. Neural progenitors are critical for normal brain development, differentiating into neurons or astrocytes depending upon their environmental context. Neural progenitors are permissive for HIV-1 infection, but we do not understand how HIV-1 affects their function or distribution. We hypothesize that HIV-1 negatively impacts progenitors, and that this in turn contributes to PE. Using archived pediatric brain tissue from HIV-1+ and control HIV- children, we will seek to answer two specific questions this summer: a) are there fewer neural progenitors in neurogenic regions of the developing brain of HIV+ compared to HIV- children; and b) are the number of astrocytes increased, with evidence of astrocytic activation (astrogliosis) in HIV+ tissues compared to HIV-? Student responsibilities in this project will include fluorescence immunohistochemistry, microscopy and image analysis under the guidance of the lab mentor and technical staff. Prerequisites would be computer literacy, plus familiarity with statistical concepts and Excel. Photography experience a plus.

Huafeng Wei

Mechanism of neurotoxicity induced by inhaled anesthetics

This project will test the hypothesis that isoflurane, a common inhaled anesthetic, induces cell apoptosis by causing excessive calcium release from endoplasmic reticulum via over activation of IP3 receptor. Our preliminary data demonstrated that isoflurane was more toxic in DT40 chicken B lymphocyte wild type than in DT40 with total IP3 receptor knock-out (DT40 IP3 TKO). These results suggested that activation of IP3 receptor plays important roles in isoflurane-induced neurotoxicity. We will continue to study the effects of isoflurane on induction of cell death by apoptosis, disruption of intracellular calcium homeostasis and changes of apoptosis-regulatory proteins (Bcl-2, Bax) in two types of DT40 cells. We will measure the changes of calcium concentrations in cytosolic space, mitochondria and endoplasmic reticulum after isoflurane in two different type cells. In addition, we will compare the neurotoxic effects of isoflurane with two other new inhalational anesthetics, sevoflurane and desflurane. This study may provide important clues if inhalational anesthetics act on IP3 receptor for its mechanisms to induce neurotoxicity. The summer students is expected to assist routine cell culture, cytotoxity assays for cell apoptosis or death, Western blot to determine changes of apoptosis regulatory proteins and measurement of changes in intracellular calcium concentration. The proposed research work will be under the direct supervision of mentor or the senior scientist in the lab. Previous experience in the biomedical research, especially proficiency in scientific paper writing, will be very helpful to this ongoing research project.

Harold Dibble

Old Stone Age Archaeology in France

For the summer of 2008 I will be directing an archaeological excavation in France, at the Middle Paleolithic site of Roc de Marsal. This project provides ample opportunity for the undergraduate student to learn about archaeology and to participate fully in the research endeavor. During the summer the student will be trained to use a total station for mapping and also will receive training in the other computerized methods we employ (including artifact processing, analysis, and photography). Moreover, s/he will also rotate through the full range of other duties in order to gain the broadest possible experience. Information about the project, as well as background to the methodology used, etc, can be found at www.oldstoneage.com. There are no pre-requisites beyond an interest in archaeology, and the student must be physically fit.

Eduardo Fernandez-Duque

Male-female relationships and biparental care in titi monkeys of Ecuador

This study is part of a long-term research program to investigate monogamy and parental care in primates of Ecuador and Argentina. We are now beginning a study of monogamy and paternal care among the titi monkeys of Amazonia. Titi monkeys live in small, monogamous groups in which the male and female form a very strong bond. Unlike any other known primate, males provide most infant care, and the infant develops a stronger bond with its father than with its mother. Some of the questions we plan to address are: How do male and female titi monkeys share the care of their offspring? How do they maintain the pair bond between them? Is there aggression and competition among males and females of this monogamous species? The specific objectives of the study to which students will contribute are: 1- to observe male-female and adult-infant interactions, 2- to habituate some of the groups, 3- to collect fecal samples for DNA analysis of paternity, 5- to collect fecal samples from males for analysis of testosterone levels when they are providing infant care and when they are not. The project will take place in Ecuador at the Tiputini Biodiversity Station of the Universidad San Francisco de Quito. The students will assist in collecting behavioral, morphological and fecal data from five radiocollared groups during all-day follows that begin at dawn and finish at dusk. They will also collaborate in the processing of samples and organizing of data. No Spanish is required.

Behavioral and Hormonal Correlates of Paternal Care in Owl Monkeys of Argentina

Why do some male monkeys mate in a monogamous relationship presumably foregoing other reproductive opportunities? Why do they invest so heavily in the care of offspring they are not certain to have sired? The evolution and maintenance of monogamy in Neotropical primates that show intensive paternal care remains an enigma. This study is part of a long-term project that examines social monogamy in Neotropical primates of Argentina and Ecuador. During the mating season of 2008, we will study male-female social relationships and patterns of infant care in owl monkeys (Aotus azarai) in Argentina to evaluate the hypothesis that the care and services provided by males are important in the maintenance of monogamy. Using fecal samples, we will also evaluate male and female reproductive hormonal profiles to test the following: i) the extent to which males are precluded from polygyny because of female reproductive synchrony, ii) differences in testosterone profiles that may be related to parental behavior, and iii) the possible trade-off between parental care and territoriality as reflected in testosterone levels. These data will allow the first tests ever on the possible hormonal mechanisms regulating monogamy in these species. The students will be responsible for locating a different owl monkey group each day using radio-telemmetry and for collecting fecal samples from the individuals in the group. To accomplish that, they will need to follow the group during long hours between dawn and dusk. Students must be culturally sensitive and willing to live in very modest conditions during their field stay. Some conversational Spanish a plus.

Louise Krasniewicz

Gaming and Gambling in Human History

Gaming and gambling are activities found in cultures throughout the world and across time. This project, which will eventually lead to a publication, an exhibit and a website on gaming and gambling from our prehistoric past up to present-day Philadelphia, looks at gaming as a human encounter with chance and fate. This anthropological approach, rather than a psychological or medical one, is dependent on showing that cultures throughout the world depend on gaming of all sorts to talk about important issues like who controls fate and the future, what is luck, what risks are worth taking, and what does it mean to take a chance on the unknown. This study is utilizing the world-famous 19th-century gaming collection of the University of Pennsylvania Museum of Archaeology and Anthropology in order to show how different cultures have used gaming fre these very social and culturally important activities.
The student working on this project will have an opportunity to work with both the artifacts in the museum’s collection and the related archaeological and anthropological literature. The student will help develop a database of the gaming artifacts in the museum’s collection, incorporating hundreds of photographs already taken and assist with the photographing of hundreds of other objects. He/she will also research the artifacts in the anthropological literature as to their names, uses, related rituals and other documentation. In addition, a collection of articles from the anthropological and archaeological literature will be developed. The research may include trips to other museum collections to view their gaming artifacts and archives. There are no pre-requisites for the position but the student should be able to organize large amounts of information efficiently, take initiative when encountering new leads on relevant information, and enjoy working with artifacts and early anthropological and archaeological literature.

Theodore Schurr

Clinical Droplet Keratopathy in the Mapuche Indians of Western Argentina

Climatic droplet keratopathy (CDK) is an acquired, often bilateral degenerative corneal disease with a high prevalence in certain regions, characterized by progressive opacity of its anterior layers. Although the etiology of CDK is unknown, it is considered a multifactorial disease. To explore the role of population-based genetic effects in CDK cases among the Mapuche descendants of the northwest area of Patagonia in Argentina, we have characterized mitochondrial DNA and Y-chromosome diversity in 57 individuals to determine their genetic ancestry. This analysis demonstrated that nearly all persons had a Native American mtDNA background, whereas 50% of the CDK group and 37% of the control group had Native American paternal ancestry, respectively. Although the Y-chromosome data also revealed differences in specific haplogroup frequencies between these two populations, there was no statistical significance between individual paternal genetic background and incidence or stage of disease. These results indicate that genetic ancestry is much less of a factor in the expression of CDK than for other complex diseases involving metabolic and bioenergetic processes. The next step in this analysis, which will be conducted by a student from the PURM program, is to examine the role of variation in aldehyde dehydrogenase 3A1 (ALDH3A1) gene in CDK expression. ALDH3A1 comprises a surprisingly high proportion (5-50% depending on the species) of the water-soluble protein of the mammalian cornea, but is present little if at all in the cornea of other species. Several studies have demonstrated that this abundant corneal protein plays an important role in the protection of ocular structures against oxidative damage. Corneal ALDH3A1 appears to protect against UV-induced oxidative stress through a variety of biological functions such as the direct absorption of UV-light and the scavenging of reactive oxygen species (ROS). To determine whether mutations in this gene are related to CDK expression in Mapuche individuals, the ALDH locus will be PCR amplified, sequenced and read on an ABI 3130XL Gene Analyzer in the Laboratory of Molecular Anthropology at Penn, and the resulting data compared with clinical information to ascertain any genotype-phenotype correlations. Given the nature of this project, the PURM student should have a background in biology and genetics, and hopefully also some laboratory experience prior to beginning the project.

Genetics and Behavior in Owl Monkeys from the Argentinian Chaco

This project is investigating how primate social systems are shaped by ecological and social conditions. More specifically, it is exploring the contributions that males and females make to the maintenance and evolution of a monogamous social system in owl monkeys (Aotus azarai) from the Argentinean Chaco. In this project, we are combining long-term behavioral and demographic data with molecular genetic data to examine the genetic structure of the population, as well as the evolution and functioning of socially monogamous groups. We are presently characterizing maternal genetic variation and female transfer (mitochondrial DNA), and analyzing the kinship structure of monogamous groups and the sub-population (microsatellite analysis). In the next step, we will test whether a socially monogamous relationship implies genetic monogamy, i.e., paternity assessment, through the analysis of Y-chromosome markers. For the Y-chromosome analysis, which will be conducted by a student from the PURM program, we will analyze single nucleotide polymorphisms (SNPs) on the Y-chromosome. Using the primers employed by Aitken et al. (2004) to target specific genes on the Y-chromosome, samples will be PCR amplified, sequenced and read on an ABI 3130XL Gene Analyzer in the Laboratory of Molecular Anthropology at Penn. This approach will identify SNPs present in the non-recombining region of this chromosome that are likely to reveal paternal lineages within this species. We will also employ the protocol of Moreira (2002) to identify SNPs in the sex determination region (SRY) gene for the same purpose. Given the nature of this project, the PURM student should have a background in biology and genetics, and hopefully also some laboratory experience prior to beginning the project.

Analysis of mtDNA variation in archival hair samples from Native American populations

At the turn of the 20th century, Franz Boas and his colleagues in the Jesup North Pacific Expedition collected extensive biological and cultural data from native Siberian and Native American populations from North America. Included amongst the samples obtained during this twenty-year study are hair samples from thousands of individuals belonging to dozens of different tribes. These hairs are currently being stored in the Department of Physical Anthropology at the American Museum of Natural History in New York City. I have submitted a request to analyze these samples for genetic variation at Penn, and anticipate receiving permission to do so and access to the samples within 1-2 month’s time. The data from these individuals will greatly expand our understanding of Native American population variation and history, and complement my laboratory’s on-going research with contemporary tribes in North America. Furthermore, because the hairs were collected from individuals from whom physical trait measures were also collected by Boas and his colleagues, we will have an unprecedented opportunity to compare patterns of population diversity based on both anthropometric and genetic evidence from the same populations, some of which may no longer exist today. To undertake this study, we will try and obtain 4-7 hairs per person for analysis, due the fact that not all hairs will contain the same amount of DNA, and then extract genomic DNA from them. Ideally, all of the hairs will contain a root and a shaft, as the DNA tends to be concentrated in the root, but this may not always be the case. We will also request hairs from between 30-50 individuals per tribe, perhaps more if the tribe is large, to ensure that we have obtained a representative sample from each populations. Under my guidance, the student from the PURM program would extract DNA from these hairs and then analyze mtDNA variation present in the samples through direct sequencing and single nucleotide polymorphism (SNP) typing carried out in the Laboratory of Molecular Anthropology at Penn Given the nature of this project, the PURM student should have a background in biology and genetics, and hopefully also some laboratory experience prior to beginning the project.

Brian Spooner

Globalization Research Tool

A student research assistant is required for collaborative work on the development of a research tool for the study of globalization. This project is co-directed by Lee Cassanelli (History), Mauro Guillen (Management), and Brian Spooner (Anthropology) and designed to support, coordinate and promote interdisciplinary research in this field. The most visible product is a website (at www.globalizationstudies.upenn.edu) that apart from providing classified links to a wide range of globalization-research projects, both on and off campus, provides access to several hundred databases, and demonstrates ways to use them in research involving the indexing, assessment and theoretical discussion of various aspects of the overall globalization process. The project interrelates quantitative with qualitative data, and with evolving opinion.
The student will assist on a daily basis in collection and classification of data. Each participant is assigned a particular geographical area or thematic sector and is mentored closely by a participating faculty member. Working group meetings are held weekly throughout the summer, in which participating faculty and graduate as well as undergraduate students report on their work, and participate in the development of research methods, testing of hypotheses, and theoretical discussion. Social-science background is preferred, but history, music, linguistics and comparative literature are also possible fields.

Claudia Valeggia

Monitoring reproductive hormones of human and non-human primates

This laboratory experience will take place in the Reproductive Ecology Laboratory of the Department of Anthropology. We are currently working with several assays for reproductive hormones (estrogen, progesterone, testosterone) that will help us monitor the reproductive status of male and female titi and owl monkeys in the field. In our laboratory, we analyze fecal samples from these monogamous monkey species to evaluate the hormonal changes that occur during their reproductive cycle. In particular, we are interested in investigating changes during the mating season and before and after the birth of infants. The lab also uses enzyme-immunoassays for the analysis of hormones in women and men in different populations. We are interested in investigating how different ecological contexts and subsistence activities may be reflected in hormonal profiles. For example, we are monitoring the reproductive physiology of women of indigenous groups in South America who are going through a dramatic change in lifestyle.Student duties: The student will join the laboratory team in all the steps involved in assay set up and running, from processing of fecal and urinary samples to reading results of the assays. She/he will also participate in data entry and analysis, and supporting activities such as laboratory maintenance and organization, and bibliographic searches. Opportunities for developing senior theses and independent projects are possible. Any type of lab experience would be helpful, though not essential.

Hormonal correlates of puberty in a population of Toba girls in northern Argentina

This study is part of the Chaco Area Reproductive Ecology (C.A.R.E.) Research Program. The C.A.R.E. Program studies the interrelationships between the physical and social environment and reproductive biology of men and women of the Gran Chaco area in northern Argentina. This study focuses on puberty, a key transition in human life history that marks a shift in allocation of metabolic energy from growth and development to reproductive function. We are investigating how changes in energy allocation are effected during puberty and how the mechanisms underlying these allocation changes are linked to reproductive maturation. The study population, the Toba of Namqom, is located in the province of Formosa, Argentina. We are collecting the following data: life history (through interviews), anthropometrics (weight, height, % fat), and urine samples for the measurement of C-peptide of insulin, growth hormone, and ovarian hormones (estrogen and progesterone). Student responsibilities: The student(s) will travel to the field site during the summer and assist in all steps of the study. Activities include interviewing girls, collecting urine samples and anthropometric data, organizing daily and weekly research schedules, interacting with local assistants, socializing with the local population, processing urine samples, data entry, and team meetings. Requisites: Well-developed cultural sensitivity, a good command of Spanish (fluency a big plus!), and tolerance for simple living and extreme weather conditions. There are opportunities for developing independent projects or senior theses stemming from this study.

Jason Burdick

The Polymeric Biomaterials Laboratory (PBL) investigates the design of novel materials with unique properties towards the development of translational therapeutics or for fundamental studies of cellular behavior. One area that my laboratory is exploring is the development of water-swollen networks (hydrogels) that incorporate o-nitrobenzyl groups into the network crosslinks so that network crosslinking can be controlled with light exposure. O-nitrobenzyl groups photo-rearrange when exposed to various wavelengths of light to yield a free alcohol or amine and an o-nitrosobenzyl aldehyde or ketone. There are only a few examples where these groups have been used in biomaterials, despite their many potential advantages. The use of photo-rearranging groups presents opportunities to spatially (with photomasks and light exposure) and temporally (with intermittent light exposure) control polymer structures. We are investigating this tool towards the engineering of advanced scaffolds for tissue regeneration and to control adult stem cell) behavior. This project will investigate spatial control over cell migration by designing hydrogels with multiple types of crosslinks, where sacrificial crosslinks can be cleaved with light exposure to provide an environment permissive to migration. From a design standing, parameters such as initial crosslinking density, ratios of the different crosslinks, type of pattern, and hydrogel dimensions will play a role in material development. The undergraduate student will work closely with laboratory members on the synthesis and polymerization of these hydrogels, characterization of the interactions of the stem cells with the hydrogels, and imaging and quantifying stem cell migration in the materials.

Ravi Radhakrishnan

Molecular Systems Biology via Multiscale Modeling and High-Performance Computing -1

The penny dropped after the human genome was sequenced and it was realized that simply knowing the sequence wasn't going to answer many of the biological questions. There has been a growing effort to figure out in a concerted way, underlying mechanisms of biological processes, by theoretical, computational, and experimental means, and to ask questions that enables us to gain an unprecedented level of understanding and where precise prediction, control, and design are feasible. We are involved in developing and applying multiscale algorithms that enable predictive modeling of complex system behavior across multiple scales encompassing enzyme catalysis, protein conformational changes, single molecule manipulations, and intracellular signal transduction. The objective of the SysB (systems biology) focus group (mostly consisting of undergraduate students) I lead is to explore signaling networks at the subcellular level, their dynamic behavior, robustness, sensitivity to mutations in individual enzymes etc. The applications are largely synergistic with the rest of our research program. For example, in one application, we are applying network analysis of delineate differences in signaling between normal and cancer cells. In another application, we are exploring the cooperativity between cellular membranes and membrane-bound curvature inducing proteins to mechanistically describe the intracellular internalization process known as endocytosis. This latter project has overlap with our drug delivery as well as our cancer therapeutics initiatives. Students interested in being part of the SysB group need to have a solid mathematics and physical sciences background in addition to knowing basic cell biology. Familiarity with computing is a plus.

Molecular Systems Biology via Multiscale Modeling and High-Performance Computing- 2

Because the therapeutic effects of many drugs are accompanied by serious toxicity and severe side effects, new experimental methods of targeted drug delivery are under development. Drug carrier binding can be increased selectively by incorporating membrane specific molecules that adhere to receptors or ligands that are uniquely expressed or overexpressed within diseased tissue relative to normal tissue. We propose to develop a multiscale model of transvascular drug delivery using nanocarriers initially delivered into the vasculature. The carrier is deformable and laden with a diffusible drug (e.g., antineoplastic, antiarrythmic) and its surface is also coated with ligands specific for receptors preferentially expressed on the luminal surface of endothelium. Our models will account for motion of the nanocarrier within sufficient proximity of the endothelial surface for binding to occur. Because of the interdependency of the coupled transport events occurring between the flowing blood and the endothelial surface, the modeling will incorporate and bridge multiple scales (e.g., continuum mechanics, molecular mechanics and molecular dynamics, stochastic methods). This novel work will serve two major purposes. First, it will provide important results for application to intelligent design of drug delivery systems for the targeted treatment of diseases where no integrative modeling of the multiple micro- and macro-scale mechanics currently exists. Second, it will provide important new computational methods for modeling of biofluid dynamics and biotransport systems integrating multiple length and time scales. This project is ideally suited for undergraduate students with inclination for mathematics, physical sciences, and cell biology; familiarity with computing is a plus.

Molecular Systems Biology via Multiscale Modeling and High-Performance Computing- 3

High accuracy synthesis in DNA replication and repair is a prerequisite for the integrity of our genome. This venerable surveillance job of accurate duplication despite occasional DNA damage falls in large part on DNA polymerases which, during DNA replication and repair, incorporate nucleotides to the primer strand complementary to the template bases. Since mutations stemming from polymerase errors can result in permanent genomic change that may lead to human diseases like colon, skin, or lung cancer and premature aging, understanding fidelity mechanisms is of great scientific and biomedical importance. The fidelity of DNA polymerases refers to their ability to choose correct nucleotides from a pool of structurally similar molecules. Across the many known polymerases, fidelity varies from one to nearly one-million base errors per one-million nucleotides synthesized. Our prior molecular simulation studies on polymerases have suggested a richly orchestrated set of molecular events that are essential to the nucleotide incorporation process. We plan to extend these studies to scenarios in which the polymerases incorporate mismatches and carcinogens. Our modeling platform is expected to establish a new paradigm to view molecular carcinogenesis and establish a scale for genotoxicity of carcinogens. Such information will help better understand the processes by which damaged DNA gets incorrectly processed eventually leading to mutations and human diseases. Our studies have immediate applications development of polymerase inhibitors which are in use in treatments for combating HIV, cancer, and premature aging. Undergraduate students will gain hands-on modeling experience and experience high-performance computing and scientific visualization.

Casim Sarkar

Design of ‘smart’ peptides through directed evolution

The Molecular Cell Engineering Laboratory (http://www.seas.upenn.edu/~caslab/) seeks a highly motivated student with keen interest in developing novel biomolecular therapeutics. The summer project will entail the screening of engineered peptide libraries in order to isolate novel amino acid sequences that are capable of sensing changes in environmental pH, salt, or temperature. These ‘smart’ peptides will have direct utility in drug delivery, biomaterial design, and biosensing applications. Using modern techniques in molecular biology, we can mimic the process of Darwinian natural selection in the laboratory (on a much more rapid timescale) to evolve the amino acid composition of individual peptides or proteins for specific biochemical or biophysical properties. This approach, known as directed evolution, can be applied to generate and screen over 1 trillion unique variants in only a few weeks by using a powerful platform: ribosome display. The student will learn the basic technique of ribosome display and will perform vital preliminary experiments with a designed peptide library to isolate desired sequences. The student will also have the opportunity to learn the experimental methods for mimicking natural selection in the laboratory. A basic understanding of transcription and translation is necessary. Any type of lab experience would be helpful, though not essential. There is also the possibility to continue working on the project beyond the summer.

Diana Zuckerman

Health Policy: A Capitol Hill Experience

This project involves research to compare and contrast federal legislative initiatives involving health policy, including health care reform proposals, SCHIP (the State Children’s Health Insurance Program), and other efforts to improve health care. Diana Zuckerman, Ph.D., who worked in the U.S. Senate, House of Representatives, and White House, will mentor the student. In addition to research and writing, the student will also attend Congressional hearings and strategy sessions of a coalition of nonprofit organizations working to improve health policies. The student should have excellent oral and written communication skills and be able to work independently and as part of a team. An interest in public policy is important, and course work in government or public health is preferred but not required. Applicants should have the maturity to work with policy professionals as well as other interns.

Consumer Product Safety Commission: Safe Toys and Safe Products

This project involves research on proposed legislation to improve the Consumer Product Safety Commission, a small federal agency responsible for the safety of toys, bicycles, and other children’s products; car seats; and many other products used by adults and children. Diana Zuckerman, PhD, who worked in the U.S. Senate, House of Representatives, and White House, will mentor the student. In addition to research and writing, the student will also attend Congressional hearings and strategy sessions of a coalition of nonprofit organizations working to improve the Consumer Product Safety Commission. Student should have excellent oral and written communication skills and be able to work independently and as part of a team. An interest in public policy is important, and course work in government, public health, and statistics, is preferred but not required. Applicants should have the maturity to work with policy professionals as well as other interns.

Are Medical Products Safe for People of Color? For children?

This project involves reviewing and summarizing research that was previously conducted on drugs, medical devices, and vaccines that were reviewed by the Food and Drug Administration (FDA). The FDA makes decisions about whether to approve medical products based on research conducted by the companies that make those products. Although encouraged to include diverse populations in these studies, the companies are not required to do so. As a result, some medical products are approved for all adults based on studies of white men and women. Some medical products are used for children, despite being studied only on adults. The student will review dozens of studies conducted in the last 9 years and calculate the number of people representing different racial, ethnic, and age groups who were included in the clinical trials provided to the FDA. The student will also review documents regarding whether racial, ethnic, or age differences could be relevant to safety or effectiveness of the specific product. Dr. Diana Zuckerman, who worked in the U.S. Senate, House of Representatives, and White House, and who is a nationally-recognized expert on the FDA, will mentor the student. In addition to research and writing, the student will also attend Congressional hearings, FDA Advisory Committee meetings, and strategy sessions of the Patient and Consumer Coalition, which is a coalition of nonprofit organizations working to improve the FDA. Student should have excellent oral and written communication skills and be able to work independently and as part of a team. Knowledge of basic statistics is required. Course work in government or public health is preferred but not required.

Ted Abel

Molecular Mechanisms of Long-Term Memory Storage

One of the hallmarks of long-term memory storage is that it requires the synthesis of new genes and new proteins, which act to alter the strength of synaptic connections within appropriate neuronal circuits in the brain. Indeed, experiments first carried out over forty years ago have shown that protein synthesis and transcription inhibitors selectively block long-term memory in a variety of organisms and a number of behavioral tasks. The challenge has been to define the molecular mechanisms by which gene regulation occurs and to identify how these biochemical changes act within specific neural circuits to alter behavior. Initial work examined the role of individual transcription factors, with a focus on those transcriptional regulatory proteins that are modified by cellular signaling pathways activated by neuronal activity and neurotransmitter receptors.

Mechanisms of transcriptional regulation during memory storage

How are the various signals acting on a neuron integrated to give rise to appropriate changes in gene expression? How are changes in gene expression maintained to sustain memories for days, months and even years? Our work has revealed that transcriptional coactivators, such as CREB-binding protein (CBP) represent the critical molecular switches that integrate signals via multiple signaling pathways and multiple transcriptional regulatory proteins. Further, CBP is a histone acetyltransferase capable of the epigenetic modification of chromatin. These epigenetic marks act to stable alter the expression of specific sets of genes during the consolidation of long-term memory. We have been taking a genetic approach to define the role of CBP and a related coactivator p300 in long-term memory storage. Our work has revealed long-term memory deficits in genetically modified mice in which CBP function has been impaired by transgenic expression of an inhibitory form of CBP or in mice that carry a mutant form of CBP unable to be recruited to DNA by the transcription factor CREB. Using pharmacological approaches, we have transiently increased histone acetylation in the hippocampus during memory consolidation using HDAC inhibitors. This pharmacological increase in histone acetylation results in enhanced memory storage and increased synaptic strength. Thus, our work suggests that epigenetic mechanisms of chromatin modifications mediate the storage of memory in neuronal circuits within the brain. A critical question now is to identify the genes whose expression is coordinately regulated by epigenetic during the consolidation of long-term memory. These experiments are currently underway using quantitative PCR, microarray analysis and chromatin immunoprecipitation

Where is the cAMP/PKA signaling pathway activated within neurons during memory storage?

One of the challenges in the study of signal transduction pathways in neurons is how the synapse specificity of synaptic plasticity is maintained in the face of diffusible second messengers, such as cAMP, and diffusible proteins, such as the catalytic subunit of PKA. This is especially true for long-lasting forms of synaptic plasticity and long-term memory storage that involve changes in gene expression, for there is only a single nucleus even though a neuron may have thousands of individual synapses. One way in which neurons solve this problem is to restrict PKA to specific subcellular locations via interactions between PKA and A-kinase anchoring proteins (AKAPs). Therefore, we are addressing the role of PKA anchoring in hippocampal synaptic plasticity and memory storage using genetic and pharmacological approaches. Our initial studies have revealed that PKA activity and PKA anchoring is required for synaptic tagging, the process by which plasticity-related proteins are “captured” by activated synapses. We are now investigating which AKAP signaling complexes are crucial for these processes and defining the behavioral role of PKA anchoring. This analysis will be extended to identify the substrates of PKA targeted by anchored kinase, enabling us to determine the pool of AKAP complexes and PKA substrates that are required for synaptic tagging and capture.

Fevzi Daldal

Cytochrome c maturation in living organism

The long-term goals of this project are to define the nature, mechanism of function and biogenesis of cytochromes (cyt). Cyts are ubiquitous hemoproteins that are key electron carriers in energy and signal transduction pathways essential for cellular processes spanning from ATP production (chemical energy) to cell death induction (apoptosis). We seek a mechanistic understanding of energy transduction pathways, including photosynthesis (Ps) and respiration (Res), using the facultative phototrophic bacteria of Rhodobacter species, which provide excellent experimental models for these studies. We aim to understand how cells make c-type cyts (cyt c maturation, CCM), and how these proteins are assembled into functional membrane complexes (cyt c biogenesis). This is an important biological process, and our work uncovered the R. capsulatus CcmI, CcmE, CcdA and DsbA-DsbB components of CCM. Ongoing work focuses on the interactions between the CcdA-CcmG-DsbA proteins of the periplasmic thio-redox loop, and on the putative CcmHFI heme ligation core complex. CCM studies are of general interest as many of the components are involved in other cellular functions, including protein translocation, extracytoplasmic protein folding and degradation, redox homeostasis and metal trafficking. Immediate goals include characterization of the interactions between the periplasmic thio-redox loop components (CcdA, CcmG and CcmH) of CCM and apocyt c. We also probe whether the CcmH, CcmF and CcmI form a heme ligation core complex, and molecular genetic and biochemical characterization of the postulated CcmHFI core complex is pursued to probe its occurrence and interactions with other CCM partners. We use molecular genetic and genomic/proteomic as well as biochemical/biophysical approaches to probe whether this loop ensures efficient capture of, and stereo-selective heme ligation to, the apocyts. As an excellent preparation for graduate school application, the student involved with this project will learn how to produce and characterize informative mutants. Techniques of protein purification and characterization, as well as immunological probing of protein-protein interactions and use of proteomic and mass spectrometry to seek novel components will be used.

Human sideroblastic anemia

The objective of our work is to identify mitochondrial protein biomarkers for bone marrow failure (myelodysplastic syndromes), including sideroblastic anemia, Fredrich’s ataxia and secondary acute myelogenous leukemia. The frequency of myelodysplasia increases dramatically with age, ranging from 4 per 100,000 in children to over 30 per 100,000 in older adults. About 15-20% of myelodysplastic patients exhibit a blood disease called sideroblastic anemia. Patients with this disease exhibit iron accumulation in mitochondria of bone marrow red cell precursors. Generally, signs and symptoms of this disease are those of anemia with pallor and fatigue. Progression to myelogenous leukemia occurs in about 10% of cases. Molecular and biochemical bases for myelodysplasia are unknown, but iron accumulation in the mitochondria of sideroblastic anemia cells suggests a connection to iron metabolism and mitochondrial dysfunction. Hence, to investigate these connections, we study mitochondria from blood cells of patients with myelodysplasia. We were the first to undertake a proteomic approach to identify proteomic and functional differences that underlie myelodysplasia. Initial focus is on proteins and processes related to iron metabolism in mitochondria, and ongoing works involve purification of different mitochondria-containing cells from peripheral blood (platelets, neutrophils, lymphocytes and reticulocytes) and analysis of their protein contents using 1D and 2D gel electrophoresis, coupled to mass spectrometry (nLC-ESI-MS/MS) and other proteomic and genomic approaches. Giemsa or Methylene Blue staining, FACS analysis and fluorescence microscopy are used for assessing the purity of cell preparations. Of special interest are the proteins that are abnormal in patient reticulocyte, platelet, mononuclear cell and neutrophil mitochondria but normal in lymphocyte mitochondria, as these proteins may represent disease biomarkers. As an excellent preparation for medical school application, the student involved with this project will learn how to work with human blood to purify appropriate cells, isolate their mitochondria and participate in their analyses. Identified proteins from normal healthy volunteers (ie the investigators) will be compared with those from diseased patients as molecular biomarkers. The proteins and their corresponding genes will be studied in patients under treatment to monitor the progression of disease and the patient’s response to treatments, and eventually, will be used for development of specific clinical diagnostic tools for these diseases.

Doris Wagner

Genomic Investigation Of Transcriptional Regulation

One research program in my lab focuses on the switch from vegetative to reproductive development in the plant model system Arabidopsis thaliana. This is a vital developmental transition. One master transcription factor is sufficient to trigger this switch. It does so by reprogramming cells that will give rise to the relevant structures. We have used a genomic approach to find the direct targets of this transcription factor. Identification and characterization of these targets will reveal how the transcription factor regulates the switch to reproductive development. Briefly we used a method called chromatin immunoprecipitation (ChIP) coupled with whole genome microarray hybridization to find the regions in the genome bound by the transcription factor. We are looking for a highly motivated undergraduate to join in the computational and molecular analysis of the large-scale genomic dataset we generated. The project will focus on verification of the bound regions and thus genes regulated by the transcription factor, coupled with monitoring expression changes in these genes in response to activation of the transcription factor. Laboratory techniques to be employed include state-of-the-art molecular approaches such as chromatin immunoprecipitation (ChIP), real-time PCR, and expression studies (microarray-based) as well as computational analysis of the datasets generated. Computational approaches to be employed will include motif and sequence analysis and statistical analysis of the microarray data. The ideal undergraduate researcher would be interested in both wet and dry lab activities and have strong programming skills, including fluency in Python or PERL. Research can be continued in the lab as independent study (BIOL399/499) if desired.

Function And Recruitment Of Chromatin Remodeling Activities

Another research area in my lab focuses on how transcription factors and other proteins that need to contact DNA in the nucleus of eukaryotes can access DNA compacted into chromatin. In recent years it has become clear that regions of the DNA are made accessible by relieving chromatin compaction in response to environmental signals or in a tissue and stage specific fashion. Specialized activities open up the chromatin to allow proteins to access DNA. One of these activities is chromatin remodeling. We study chromatin remodeling in the plant model system Arabidopsis thaliana. The critical role of chromatin remodeling is highlighted by the finding that chromatin remodelers are tumor suppressors in mammals. Two projects are available on this topic. One examines the biological role of two as yet uncharacterized chromatin remodelers using phenotype analysis of mutants, genetic interaction studies and expression studies using a reporter system. The other project investigates the recruitment of these activities to the region of the genome where they are required. This is of central importance, because this will decide which genomic region will be “readable”. Techniques involved in this project include protein interaction studies in yeast (yeast two-hybrid assays) and in plant cells (using Bimolecular Fluorescence Complementation), as well as co-purification of the interacting proteins expressed in E. Coli followed by Western hybridization. Research can be continued in the lab as independent study (BIOL399/499) if desired.

Marisa Bartolomei

Analysis of the Epigenetic Modifications at the MECP2 locus

Rett Syndrome (RS), which is an autism spectrum disorder, is primarily caused by mutations in the X-linked gene encoding the methyl binding domain protein MECP2. This syndrome exhibits considerable phenotypic variation, which is partially attributed to the effect of X chromosome inactivation. Females with RS are typically heterozygous for the mutation. That is, all cells undergoing X inactivation in the female are functionally hemizygous for MECP2. If the mutant allele is on the active X chromosome in a given cell then that cell will have no wild-type MECP2. Recent work has shown that the effects of loss of MECP2 can be reversed in the mouse, suggesting that restoring expression of MECP2 in affected human patients can also reverse the detrimental phenotype. Whereas the mutations in the mouse were genetically induced and reversed and cannot be applied as such to humans, other therapeutic options such as drugs that target epigenetic modifications, siRNAs or small molecules could be used to activate the copy of the gene that is on the inactive X chromosome. Genes on the inactive X chromosome are stably silenced through a variety of epigenetic modifications. Nevertheless, it is possible that certain genes may be more easily activated given the observation that the human X chromosome harbors a number of genes that escape X inactivation in females. Our goal is to investigate the epigenetic modifications within the MECP2 locus in cells lines from individuals with RS and compare these modifications with other inactivated genes on the human X chromosome. The outcome of these experiments could help guide therapies for RS patients.

Wen K. Shieh

Ethanol Tolerance of Yeast Strain Candida

The production of ethanol from lignocellulosic biomass has attracted widespread interests because of the concerns about dwindling fossil fuel supplies and soaring carbon emissions. Yeasts are by far the most popular agents used in bio-ethanol productions because of their abilities to carry out near-stoichiometric conversions of sugars to ethanol. A wild-type yeast strain, Candida tropicalis, is found to be capable of producing ethanol from various sugars (e.g., xylose and glucose), a highly desirable property in bio-ethanol productions, especially when heterogenous and recalcitrant biomass is used as the feedstock. Since ethanol tolerance (or ethanol inhibition) is a major obstacle in all yeast-mediated fermentation reactions, it is a critical issue that needs to be addressed properly in order to ensure the competitiveness of biomass ethanol productions. This project will attempt to model the phenomena of ethanol tolerance of C. tropicalis when using xylose, glucose, and mixtures of xylose/glucose as the substrates. The student will perform batch fermentation experiments in the laboratory and generate the experimental data using a variety of laboratory instruments. Various ethanol inhibition models reported in literature will be used to fit the experimental data. The models will be ranked using the appropriate statistical techniques to determine the best-fit model that will be useful in fermentor design and control. The pre-requisites include: MATH 114, CHEM 101, and CBE 160/230. A course in statistics is preferred but not required.

Feng Gai

The Gai research group in the Department of Chemistry is primarily interested in how proteins and peptides fold, aggregate and polymerize. A wide variety of biophysical and biological techniques, including laser spectroscopy and single-molecule microscopy, are used to study various aspects of these problems. For a detailed list of the current research projects, please visit our website (http://gailab4.chem.upenn.edu/). Since the Gai group has a long-standing tradition of involving undergraduates in research, those that participate in our research activities will have an opportunity to not only learn new technical skills, but also to build self-confidence in exploring the real world and develop scientific way of thinking.

Madeleine Joullie

Towards the total synthesis of Phomopsin A

The natural product phomopsin A is a hexapeptide mycotoxin found in post harvest lupin stalks and seeds infected with the fungus Phomopsis leptostromiformis. Phomopsin A and its analogues have shown to be potent microtubule polymerization inhibitors of tubulin which cause mitotic arrest (antimitotic agents) and hence can be utilized in cancer chemotherapy, as tubulin is an established chemotherapeutic target. Currently our research group has an expedient route to the formation of the unusual ether linkage contained in the macrocyclic core of the natural product ustiloxin, isolated from the fungus Ustilaginoidea virens, via nucleophilc ring opening of a trisubstituted aziridine ring. This proven methodology can be utilized to form the similar phomopsin A macrocylic core. The biological mode of action of phomopsin A at the tubulin receptor is relatively unknown although it is known to compete for the binding site of dolastatin 10 another potent antimitotic agent. The cytotoxicity of the former is dramatically lower than that of dolastatin 10. Hence the total synthesis of phomopsin A would allow for receptor mapping and determination of the biological functions within cells.
The student’s primary duties will lie in the synthesis of intermediates that can be utilized in the construction of the macrocyclic core and tripeptide sidechain of phomposin A. This will include carrying out a variety of organic reactions, purification via chromatographic methods and structure determination via spectroscopic means. The student will gain a thorough understanding of synthetic organic techniques, in particular organo-peptide chemistry and experience working as a team within an active research laboratory.

A novel approach to the Ustiloxin A.

The ustiloxins are a natural class of macrocylic peptides closely resembling the phomopsin family of peptides that were first isolated from the parasitic growths on the rice plant caused by Ustilaginoidea virens. They also exhibit mitotic arrest and hence cytotoxcity within cells. Our group has successfully completed the total synthesis of ustiloxins D and F utilizing an intermolecular nucleophilic aziridine ring opening reaction. As yet the synthesis of ustiloxin A has not been completed and the proven methodology to the other ustiloxin analogues would present a direct entry into the total synthesis of ustiloxin A. Previous synthetic endeavours completed the macrocylic ring via a peptide coupling reaction; an alternative would be to close the macrocycle via an intramolecular nucleophilic aziridine ring opening reaction. Although an unusual method of macrocycle formation in this case, it does represent a novel route to the macrocyclic core of ustiloxin A. This project will give the student first hand experience in preparative synthetic organic chemistry, with emphasis on methodology. As with the first project, the student will be exposed to a variety of reactions, purification techniques and identification of chemical structure via spectroscopic methods. The student will take an active role within the research group contributing to daily running of the laboratory and weekly group meetings.

Amy Hillier

Mapping the Du Bois Philadelphia Negro

We are recreating the foot survey W.E.B. Du Bois conducted of downtown Philadelphia in 1896 using historical census data and geographic information systems (GIS). The original survey served as the basis for Du Bois’s classic work of urban history, The Philadelphia Negro. The data we have collected will serve as the basis for an online interactive mapping application to support high school and college teaching as well as research. We hope this project will generate productive conversations about race and racism as it impacts Philadelphia today. This summer, we will continue work on developing a MySpace-like profiles section (students develop the profile of an historical person based on primary source research), board game, documentary, and after-school program related to The Philadelphia Negro and the historical data we have collected. We will also continue collecting and analyzing historical health data. Students with an interest in Du Bois, mapping, archival research, developing curriculum, or filming and editing video would be appropriate, regardless of prior experience or skill level.

Food and Exercise Diaries for Urban Places (FED-UP)

Kids who live in the city frequently stop on the way to and from school to buy junk food at corner stores, but does this impact their likelihood of being overweight or obese? Researchers have not looked carefully at the food purchasing and eating behaviors of children outside school or home, so we just don’t know the answer. We are developing a game-like instrument for collecting data about where kids buy food that we call “FED-UP” (Food and Exercise Diaries for Urban Places). FED-UP will allow kids to show the route they take to and from school using a map interface (perhaps GoogleMaps or GoogleMaps Street View). They will click on the corner stores where they stop, then identify the specific foods they purchase. We are in the process of purchasing and photographing every junk food item we can find in the corners stores and developing a database with the nutrition content information. Students with computer programming skills would be especially valuable as we develop this game, but those with an interest in children’s health and the food environment could also help us with data collection and conceptualizing the game.

System for Observing Play and Recreation in Communities (SOPARC)

This is a large, five-city study led by the Rand Corporation that involves systematically observing people in urban parks to determine their level of physical activity. The tool for collecting the data has already been tested in Los Angeles, so the goal of this study is to determine if it works in other places (that aren’t so warm) as well as to determine what aspects of parks—particular facilities or programming—are most likely to encourage physical activity. This study may start this spring or summer. Students could participate in the training to learn how to conduct the observations, conduct the observations, and help clean data. This requires no special skills, only an interest in urban parks and public health.

Michael Nairn and Domenic Vitiello

Community Gardens and the Local Food System

Urban food security is becoming an increasingly important issue. While many inner city residents lack access to fresh food, the issue is gaining more attention due to sharply rising food and energy costs as well as public health problems of nutrition and diabetes. Alternative food supply and distribution networks are growing in Philadelphia and most cities, evidenced by the rise of urban farms, community gardens, and farmers markets in many areas of the city. This project focuses on the roles of community gardens in these alternative networks. Community gardens exist in wealthy and poor communities alike, on every type of vacant land imaginable. There is, however, no comprehensive survey of them. Thus, researchers and practitioners have limited understanding of how gardens fit into the local food system. Working with the Pennsylvania Horticultural Society, this project entails designing and implementing a survey of Philadelphia’s approximately 500 community gardens. Using aerial photos, data, and maps from the Neighborhood Information System and other sources, the survey will map community gardens throughout the city and list such attributes as size, the number of families served, the income range of the surrounding community, and the whether the gardens are primarily ornamental or producing food. The student will work along with the primary researchers in developing the survey. S/he will have responsibility for basic computer mapping as well as verifying the information in the field through site visits. Some experience with Geographic Information Systems is preferred, but not required.

Food Security and the Impacts of Community Gardens

Community gardening has long been recognized in Philadelphia as a tactic for building community. Yet food production has generally been viewed as a secondary goal. However, given current issues of food justice, sustainability, and rising prices for fuel and food, local food production has become a more critical issue and goal. Community gardens have helped stabilize many neighborhoods, yet gardens face threats to their preservation since many gardeners do not have site control. Researchers at Penn and in New York have found that gardens help raise local real estate values, which in turn fosters gentrification and has led to residential development on some gardens. Yet community gardens have economic impacts far beyond real estate values. In low wealth neighborhoods especially, they enhance access to fresh, nutritious produce while decreasing the demands on household budgets in a time of inflation. The goal of the project is to research the economic impacts of community gardens and establish their importance for household and neighborhood economies. This project entails surveying 6 gardens in different neighborhoods throughout Philadelphia in depth. The student will be responsible for working with faculty to select the gardens, conduct extensive interviews with gardeners, and collect data about the types and amounts of crops grown. S/he will work with gardeners to record the amount and types of food produced at each garden. S/he will work with the faculty to calculate the retail and nutritional values of this food as well as other measurable economic, health, and environmental impacts of the gardens.

Keith Hampton

How cell phones and other technologies have changed interactions in public

This very unique project examines the impact that cell phone use and other mobile technologies (music players, laptops, etc) have had on everyday interactions in public spaces (parks, plazas, markets, sidewalks, etc). The project is based on the qualitative analysis of an archive of Super 8 time lapse films of people in public spaces in the United States and around the world over the past 35 years (the films are of informal everyday activities, not documentaries). We are looking for a student with an interest in the study of new technologies (mobile phone’s, internet use, etc) and the urban environment. Working with a small research team, responsibilities will include assisting in the conversion of Super 8 film to digital, researching literature, and using software to identify and code activities captured on film. No experience necessary, but course work in sociology, social psychology, and sociology would be an asset.

Community Informatics

The i-Neighbors project is an ongoing investigation into the specific neighborhood contexts where Internet use affords local interactions and facilitates community involvement and political participation. We are currently looking for individuals with experience in Web development to assist in the ongoing redesign of the project website. The project website (i-neighbors.org) provides social networking services to the residents of 5,000+ neighborhoods in the United States and Canada. The appropriate candidate will work with the research team to brainstorm and design new services consistent with the project goals of facilitating community participation and helping people form local social ties. The candidate must have experience using PHP and be capable of working independently.

Susan Davidson

Managing Scientific Workflow Data

Due to the availability of large amounts of online data and analytical software tools, portions of scientific experiments are now conducted “in-silico” rather than in a wet lab. As such, they can be performed extremely rapidly and generate large amounts of intermediate and final data products. This data, as well as the workflows and the executions which produced them, must therefore be carefully managed so that questions of provenance (how did this data product come to be?) and differencing (how did the workflow executions that produced two different data products differ?) can be answered. The goal of the ZOOM*UserViews is to provide an environment in which questions of provenance and differencing can be answered at multiple levels of granularity, thereby focusing user attention on what is most important to them and hiding irrelevant information.
Project participants will learn about a variety of topics, including scientific workflow systems, databases, XML, differencing algorithms, and user interfaces. Knowledge of Java required (CSE 120/121 or equivalent). Participants will work as part of an interdisciplinary team.

Ben Taskar

Movie Mashup Studio

Common video authoring tools allow you to edit videos by inserting, deleting and moving frame sequences. Wouldn't it be great to insert or remove of individual characters and objects or changing the background in movies and make them look real? We envision a semi-automatic system in which the user specifies the individual objects to insert or remove from a searchable library of segmented video fragments, and the program takes care of the seamless integration. This project draws inspiration from a popular cartoon creation studio (http://www.lacartoonerie.com/) in which the user integrates customizable cartoon characters to form a play. We have developed techniques for automated structure extraction, segmentation and indexing in video and applied it to 50 hours of film and TV footage. This project will target several aspects of high-level editing within our current system. Requirements: strong proficiency in programming, interest in film.

Seamless Image Blending

Imagine flying through videos, in the same manner you navigate the world in Google Earth or MS Virtual Earth. We are building interactive tools that allow users to navigate very large 3D scenes that are extracted from real images and video. We are interested in the seamless blending of images to remove artifacts resulting from stitching images together. These artifacts, no matter how small, are immediately perceived by the human visual system and degrade the user experience. We have a 3D reconstruction system that produces geometrically accurate 3D models from images (http://www.seas.upenn.edu/~mordohai/research.html#us). Within this project, we will design flexible, automatic algorithms for selecting which image from the set will be used to color each part of a 3D model and for blending the selected images in a way that minimizes artifacts. Programming experience required, but knowledge of specialized math or camera geometry is not.

Max Cavitch

Richard Nisbett’s Privacy and Yours

The book I’m currently working on presents a number of research opportunities for a resourceful and diligent student interested in one or more (preferably more!) of the following areas: early American history and literature; outsider art and the art of the insane; contemporary privacy law and the history of privacy jurisprudence; privacy of the dead as an ethical problem for historical research; the history of psychiatry; psychoanalysis as critical theory for humanities scholars. The project is large and multifaceted, but at its center are the writings and paintings of an early-19th-century psychiatric patient in terminal confinement at the Pennsylvania Hospital. He left behind a small number of published and unpublished writings, including an epic poem about sea voyages and monsters, and a couple of watercolors, including an extremely detailed and fanciful map of the world. For one thing, I’d like help transcribing and annotating these works, especially the map and the long manuscript poem held by the Historical Society of Pennsylvania. The researcher would also spend time working in a more exploratory way in the archives of the Pennsylvania Hospital and the Library Company of Philadelphia. In addition, the researcher would help me extend my work with secondary sources, including the vast body of work on the concept of privacy. Contemporary legislation is of special concern, as the 2003 Privacy Rule of the Health Insurance Portability and Accountability Act presents serious and complex challenges for all researchers, in the sciences as well as the humanities. I’m looking for someone who would not only be an energetic and conscientious archival researcher, but also an engaged interlocutor—someone with whom to discuss informally the ideas and the stakes of the project from a variety of perspectives.

Simon Richter

Looking for Lola: Cinema, Sexuality, and the New Woman

This project concerns a corpus of twenty films featuring a woman character named Lola, typically a dancer, who represents a new archetype of female sexuality distinctly different from the common female types—femme fatale or virtuous victim. Beginning with Marlene Dietrich in the Weimar era film Blue Angel, the name Lola has attracted the attention of a stunning array of actresses and directors, right up to the present. This project is at an advanced stage, but some primary research remains to be done. Several films still need to be analyzed in detail; the screenplay for Bombshell (in the holdings of Indiana University Library) needs to be read; archival material at UCLA and the Academy of Motion Picture Arts and Sciences in Los Angeles has to be consulted; and the cultural context for a Chinese Lola film needs to be assembled. Student and professor will collaborate on film analysis and brainstorming about thematically organized chapters. Spin-off articles are a distinct possibility. Some familiarity with gender studies, women’s studies and cinema studies would be helpful.

This interdisciplinary project concerns the 1941 film The Devil and Daniel Webster directed by the German émigré director, Wilhelm Dieterle. Although Dieterle operated primarily as a B-movie director known for his bio-pics (on Pasteur, Zola, and Juarez), this film is unusual for the remarkable constellation of issues and personalities it brought together. The original story was by the patriotic writer Stephen Vincent Benet who had already adapted his story for theater and opera and was retained for the first version of the screenplay. Dan Totheroh, a playwright and veteran of the First World War, revised the screenplay along with Dieterle. At the same time, Totheroh’s brother was working as camera man for Chaplin in The Great Dictator. Bernhard Herrmann (composer for Orson Welles and Hitchcock) provided a subtle and avant-garde soundtrack. Dieterle discussed his screenplay with the German émigré philosopher and social critic Max Horkheimer. In the course of all this collaboration, the story of Daniel Webster was transformed from a patriotic legend into a critical historical engagement with the idea of America set against the backdrop of slavery and triangle trade, the Great Depression, and the Second World War, inflected by a tradition of German literature (Goethe’s Faust) and expressionist cinema (F. W. Murnau, with whom Dieterle had trained). Student researcher will work together with professor on historical material (Webster, Medford rum, triangle trade), archival work at UCLA and the Academy of Motion Pictures in Los Angeles, film analysis, and on planning for a short monograph on the film.

Jesus and Cinema

The recent furor over Mel Gibson’s Passion of the Christ is an indication of the fraught nature of any cinematic representation of Jesus. In this project, the student and professor will undertake an initial critical viewing of the major films about Jesus, from blockbuster epics such as Ben Hur and The Robe and the silent classics of D. W. Griffith (Intolerance) and Cecil B. DeMille (King of Kings) to the provocative interventions of Scorsese (Last Temptation of Christ), Pasolini (Gospel of Matthew), Buñuel (Milky Way), Godard (Hail Mary), and Denys Arcand (Jesus of Montreal) and the more pious efforts of Zefferelli’s Jesus of Nazareth and The Greatest Story Ever Told (with Max von Sydow as Jesus), as well as comic representations such as Monty Python’s Life of Brian. Concurrently, professor and student will be preparing to approach these films from a variety of disciplinary perspectives including Christology, the quest for the historical Jesus, Jewish studies, cinema studies, art history, literary studies, gender studies and the culture wars. Are there interesting congruencies between cinema and theology or cinema and belief? How do films about Jesus test the limits of cinema, faith, and the institutions of religion? This is a project where the student can get involved in an early phase of research and see the directions things take from there.

Marjorie Margolies

Hillary Clinton for President: Un-gendering or Re-gendering American Political Discourse

I have been approached by a publisher, because of my longstanding friendship with the President and Senator Clinton, to write another book on Women and Politics, this time using Hillary Clinton’s unprecedented presidential campaign as a backdrop. This project is unique because we will have access to the campaign, its staff, contributors, high-profile supporters, and the candidate herself. My previous book A Woman’s Place which investigated women in the U.S. House of Representatives, featured in depth interviews with Hillary Clinton as well as fellow members of the Women’s Caucus. My book this time will turn the focus to campaigning, and ask the crucial questions of what it means to campaign as a woman and how we can overcome the double standards imposed on woman politicians? I am looking for a motivated student to aid in this project, someone with a passion of politics, and interest in investigating politics through a gendered lens. I have access to the Clinton Presidential Library and we would likely use this as a resource. While not necessarily offered in conjunction with my course Dealing with the Media an ideal student would either have taken this or have a strong background in politics and political communication. A high priority would be given to a student with campaign experience. Work would include research, editing, and some travel, including a likely trip to the Democratic Convention in Denver, Colorado.

Woman and Leadership: Combating Malaria in Malawi

I am seeking a student suitable to work with a distinguished policymaker on a relevant real-world problem for their research and analysis. Malawi’s Minister of Health, Marjorie Ngaunje, has been confirmed as a co-mentor for the student throughout the course of this project and will guide the student in attacking a specific facet of the huge malaria problem facing her country. Through lectures, collective discussions and research, we will identify the best practices in prevention and treatment of malaria and the ways to empower women to lead these efforts. The student will have the opportunity to work with graduates and undergraduates from all over the world, thus educating each other while working collaboratively to prepare a comprehensive final report and presentation for the Minister of Health on the very specific problem they have been tasked with. After thoroughly investigating this problem, going to experts to seek out answers, and brainstorming solutions, the student will travel to Malawi and deliver his findings to the Minister in person and begin the process of implementing his academic research by working closely with local universities, NGOs and other stakeholders. This intersection of focused academic research and real-world implementation transforms the project from being merely a classroom-based intellectual exercise to actually creating a serious blueprint for affecting change in an area where it is desperately needed. The ability and motivation to work independently is critical.

Michael Zuckerman

I am launching on the writing of a book about Benjamin Franklin. It will not be a biography so much as an interpretation of his ideas and how they do or do not hang together. The notion that informs the project is that Franklin's autobiography is a sort of last will and testament to the American people, an instruction manual on the uses of the republic, but written in code. I have written half a dozen essays on Franklin already, but they are just probes around the perimeter. It is time to get serious about the shape of the book itself. I would be delighted to have a student who would work with me on a couple of the literatures in which I am especially interested: Franklin's religion and his science. I envision the student canvassing the literature on those subjects and working up an interpretation of each during the summer. Prior familiarity with Franklin and/or 18th-century religion and/or science would be a book but not a necessity.

David Barnes

Philadelphia’s Lazaretto, Forgotten Monument to a Hidden History

This project aims to uncover the lost history of a hidden gem: the oldest surviving quarantine station in North America, which lies dormant and ignored on the banks of the Delaware River just downstream from the Philadelphia International Airport. From 1799 to 1893, the Lazaretto acted as Philadelphia’s first line of defense against invasion from yellow fever, cholera, and other devastating epidemic diseases. Students’ research for this project will recover the hidden stories of slaves, immigrants, merchants, and physicians caught up in the struggle to settle and build a young nation while protecting it from disease. It will contribute to the description of everyday life, medical care, and death in ninteteenth-century America. It will also shed new light on the nation’s long and conflicted history of immigration and public health, and contribute to scholarly debates in the history of contagionism, quarantine policy, and public health. Moreover, unlike most historical research, this work will contribute to the documentation and preservation of the historic site, and will pave the way for its restoration as a museum or other historic attraction for visitors. Students will plunge headlong into the nineteenth century, visiting various archives and specialized libraries in Philadelphia and beyond, and finding rare original documents relating to the history of the Lazaretto and nineteenth-century life in Philadelphia. They will become comfortable deciphering nineteenth-century handwriting, and will be responsible for summarizing and analyzing the documents they find. Experience with historical research is desirable but not required.

Institute for Diabetes, Obesity and Metabolism

Doris Stoffers

Pdx1 targets in pancreatic islet beta cell development

Pdx1 is a human diabetes gene and transcription factor that plays critical roles in early pancreas development and in the later identity of the pancreatic beta cell, the cell that produces the insulin required to maintain normal blood sugar. When beta cells fail to develop properly or fail to compensate for increased demand imposed by obesity and insulin resistance, then diabetes results. Our goal is to use Pdx1 as a “hook” to learn about the molecular underpinnings of beta cell development and adult beta cell functions. We have developed a unique model of Pdx1 insufficiency that revealed a critical requirement for Pdx1 in the specification of the endocrine progenitor cells that later give rise to beta cells. A high throughput cDNA microarray was carried out and revealed a list of genes whose protein products may participate in the development of progenitor cells. This project will involve the validation of interesting target genes, using basic molecular techniques as well as histological approaches to define patterns of expression during embryonic pancreas development. Initial experiments will focus on basic skills, including accurate pipetting and the conduct of experiments involving PCR. New skills and expectations will be added according to the student’s motivation and as the student demonstrates competency in basic skills. Completion of basic lecture and lab coursework in Biology and Chemistry is desirable.

Pdx1 targets in pancreatic islet compensation in diabetes

Pdx1 is a human diabetes gene and transcription factor that plays critical roles in early pancreas development and in the later identity of the pancreatic beta cell, the cell that produces the insulin required to maintain normal blood sugar. When beta cells fail to develop properly or fail to compensate for increased demand imposed by obesity and insulin resistance, then diabetes results. Our goal is to use Pdx1 as a “hook” to learn about the molecular underpinnings of beta cell development and adult beta cell functions. We have determined that Pdx1 deficiency prevents pancreatic beta cells from expanding in the setting of insulin resistance imposed by a diet induced obesity. This is due to a failure of individual beta cells to increase in size (hypertrophy) as well as a decrease in the survival of beta cells. We have also carried out cDNA expression microarrays and high-throughput chromatin immunoprecipitation coupled to promoter microarray analysis, resulting in the identification of a large panel of downstream genes and direct Pdx1 targets. Current efforts are directed toward integrating these data with the biological roles of Pdx1 to generate models of the molecular basis of islet compensation. Such models will lead to the identification of new therapeutic targets and strategies for diabetes, a global epidemic whose incidence continues to rise. This project will involve the validation of interesting target genes, using basic molecular techniques as well as histological approaches to define patterns of expression during embryonic pancreas development. Initial experiments will focus on basic skills, including accurate pipetting and the conduct of experiments involving PCR. New skills and expectations will be added according to the student’s motivation and as the student demonstrates competency in basic skills. Completion of basic lecture and lab coursework in Biology and Chemistry is desirable.

Role of a ubiquitin ligase substrate adaptor in pancreatic development: links to diabetes and cancer

Pdx1 is a human diabetes gene and transcription factor that plays critical roles in early pancreas development and in the later identity of the pancreatic beta cell, the cell that produces the insulin required to maintain normal blood sugar. When beta cells fail to develop properly or fail to compensate for increased demand imposed by obesity and insulin resistance, then diabetes results. We are investigating a novel pathway that regulates the protein stability of Pdx1. Using a yeast two hybrid approach, we found a novel interacting partner protein, called PCIF1. We now understand that PCIF1 is a substrate adaptor that recruits Pdx1 for ubiquitination and subsequent targeting to the proteasome for degradation. Mice deficient for PCIF1 express higher levels of Pdx1, resulting in increased numbers of insulin producing beta cells and improved handling of glucose. Current efforts are focused on determining the specific aspects of beta cell formation and beta cell function that are modulated by PCIF1. Another focus is on other PCIF1 substrates, including the hedgehog signaling pathway and potential links to the progression of pancreatic cancer. This project will involve basic molecular techniques, histological approaches and participation in animal physiology experiments. Initial experiments will focus on basic skills, including accurate pipetting and the conduct of experiments involving PCR. New skills and expectations will be added according to the student’s motivation and as the student demonstrates competency in basic skills. Completion of basic lecture and lab coursework in Biology and Chemistry is desirable.

Eugene Buckley

The linguistic structure of writing systems

I am writing a book about the linguistic structure of the world’s writing systems, a wide-ranging project from the earliest Sumerian and Egyptian to modern Chinese character simplification and English spelling. A student interested in the way different scripts work could help me to research details of the systems, find relevant examples, and compare previous analyses. Basic training in the necessary linguistic concepts can be provided. The specific tasks would depend on the student’s interests and background. For example, someone with interest in the Arabic script could help compile a list of Ottoman Turkish spellings and analyze the way vowels are represented. Previous exposure to other scripts is helpful, as is (for some possible projects) reading knowledge of German or French; but the only essential prerequisite is a meticulous attention to detail and a fascination with written languages.

Analysis of the Alsea language

I have a long-term project to create a complete electronic record of Alsea, a Native American language of the Oregon coast that became extinct in 1951. I began work on the language as an undergraduate myself, and over the years have built up digitized versions of the published texts and manuscript notes. The goal for this summer is an interlinear analysis of the texts. Currently the text file consists of individual Alsea sentences with English translations. With the help of specialized software, the student would help to standardize the spellings of words and to create representations that identify the subparts of each word (the root, with prefixes and suffixes). There are many open questions about the function of particular words and prefixes/suffixes in the language, which could form the basis of more specific investigation. In the course of the work, the student would learn a great deal about the structure of a language quite different from English, as well as the culture and history of the Alsea as expressed in the myths and stories. A previous course in linguistics is useful, but high school grammar and an aptitude for thinking about language could substitute.

Yoram Wind

Future of Advertising

This is a project the SEI Center for Advanced Studies in Management at Wharton is doing in cooperation with the ARF. The advertising industry is in a period of unprecedented change. We see a need to chart a path forward. The ultimate output of the project is the development of a set of empirical generalizations about advertising and a number of scenarios on the future of advertising. The empirical generalizations will summarize what we learn from the numerous experiments being conducted around the world in the last few years on what works and does not work. These scenarios can lead to the development of a series of critical experiments that will shed light on how best to succeed under changing events and macro trends. The output of the project will include a book to be published by Wharton school publishing and an associated web site and wiki format that will encourage and capture the experience of the community as we go forward. I am seeking students who are interested in working on the project by conducting research on what experiments are available and participating in a meta analysis of the currently available research. The student will also be able to participate in a conference in the fall on empirical generalizations regarding advertising. Students passionate about advertising are encouraged to apply.

Lisa Bolton

Consumer perceptions of Traditional Chinese and Western Medicine

Traditional Chinese medicine (TCM) has existed for more than two thousand years and is well recognized as an important form of health practice in China and other Asian countries. In China, traditional Chinese and Western drugs have coexisted for more than 200 years, and both types of medication are licensed as patent medicine and widely sold at drug stores and hospitals. In the United States, consumption of Chinese medicine has been growing by 25% a year since the late 1990s (The Economist 2002). However, very little comparative research has been conducted regarding these two types of medicines. The current research project investigates consumer behavior regarding TCM and Western Medicine. Specifically, we seek to understand: a) consumer perceptions of the similarities and differences between Western and TCM medicine (focusing on herbal medicines); and b) consumer preference among Western and TCM medicine as a function of disease category. We will build on research by Wang, Bolton and Heah (ongoing) on perceptions of TCM and Western medicine among Chinese consumers. We seek to extend these findings to the United States market in order to better understand how consumers perceive and purchase these products. Acting as a Research Assistant, the student will be responsible for: a) reviewing published consumer behavior literature in area; b) designing studies to investigate consumer perceptions and preference for TCM and Western medicine in the US market; c) collecting data in appropriate local markets (e.g., Asian-American groups; “Chinatown” in Philadelphia, New York, etc.); d) analyzing data and writing a report of the findings. IMPORTANT: Ability to speak/write Chinese is required for this project. Ability to work independently is also critical. This project may particularly appeal to someone with an interest in health marketing, or in cross-cultural work, or someone contemplating business or medical school.

Marketing Success/Failure Case Development

This research project aims to develop a set of cases illustrating management decisions that lead to success and failure in marketing. Prior work has established myriad reasons why businesses and new products fail. The current work focuses on gaps in managers’ understanding of the customer – the types of gaps that matter, how these gaps can lead to failure, and how closing these gaps can lead to success. It will focus on identifying and developing rich material to illustrate our understanding of the gaps in managerial perceptions of consumers and the marketplace. Acting as a Research Assistant, the student will be responsible for: a) reviewing academic, business and popular press the area to identify relevant cases or examples to illustrate these gaps; and, b) writing up mini-cases to describe these gaps, drawing upon including additional source materials where available. This project will be a bit of a cross between academic research for research and teaching purposes – some of the cases will be used for research purposes, but others may also serve appropriate in future coursework offered by the professor. IMPORTANT: The ability to write well is a prerequisite for this project. Ability to work independently is also critical. This project may particularly appeal to someone contemplating or going to business school (either as an undergraduate or later as an MBA) or someone with an interest in becoming a writer for business media.

Peter Fader

Applications of Probability Models

A mandatory pre-requisite is my elective course MKTG 476, “Applied Probability Models in Marketing.” I’m willing to work with almost any student who has taken this course and is looking for creative new applications of the techniques covered in it. By no means is the range of applications limited to marketing (or business in general) – I’m open to any area that has relevant questions (and suitable data) for the kinds of individual-level timing, counting, and/or choice processes that students will have learned in the course. I have high expectations for my research assistants – I’m looking for work that could be publishable in a top-tier journal. But I give my students all the tools and guidance they’ll need to do a great job, and I expect it will be a very productive and enjoyable working experience for them.

Ritesh Agarwal

Nanowire Memory from Reversible Crystalline-to-Amorphous Phase Transitions

This project involves studying reversible crystalline-to-amorphous phase transition-based memory switching in Ge-Sb-Te nanowires at nanometer length-scales that are not accessible by conventional fabrication techniques. Chalcogenide materials (Ge-Sb-Te alloys) are important materials for the development of electrical memory systems for data storage. The underlying principle of memory storage in Ge-Sb-Te alloys is reversible joule-heating induced crystalline-to-amorphous phase transitions that are associated with significant changes in electrical-resistivity, with low resistance state (crystalline) acting as bit-1 and high resistance state (amorphous) as bit-0. However, lithography-based fabrication techniques are finding it challenging to scale down the size of chalcogenide memory cells below 100 nm due to etching-induced material damage. Self-assembled nanowires are attractive materials as they can be easily scaled down to sub 30 nm diameters and also provide a model system to study phase-transitions at the nanoscale. Fundamental understanding and exploitation of size-dependent effects in nanowire phase-change devices holds great promise to revolutionize ultradense, ultrafast and low-power consumption electronic memory systems. The research will focus on the synthesis and characterization of Ge-Sb-Te nanowires with accurate control over composition and dimension, assembly of memory devices and studying current-induced phase switching for non-volatile data storage. The student will be expected to synthesize compositionally-controlled Ge-Sb-Te nanowires using pulsed laser depostion method and assist in characterization of samples using electron-microscopy techniques. The student will also assist in fabrication of memory devices and will perform electrical measurements to characterize and program memory storage in these novel materials. No special skills required. Highly-motivated students with general interest in nanomaterials/nanodevices desired.

Nanoscale Spectrometer

The project involves assembling a nanowire-based optical spectrometer for chemical analysis. The spectrometer will be assembled in microfluidic channels using semiconducting nanowires configured to function as light emitting diodes (LEDs) and photodiodes in-tandem. The project involves growth and characterization of semiconducting nanowires (CdS/CdSe/ZnS) with band gaps in the visible region. These n-type semiconducting wires when assembled on p-silicon substrates form a pn-junction, which if forward-biased, emits light from the wires, and if reverse-biased, can detect light as photocurrent. After the wires are grown and characterized, another critical aspect of the project is the precise self-alignment of two nanowires: LED and a detector in close proximity to each other, separated by a gap through which analytes can flow. After the self-aligned gap is formed, electrical contacts will be made to the nanowire source-detector pair, and the device will be integrated with microfluidic technology. Finally analytes will be detected under pressure-driven flow; the detection is expected to result as a drop in photocurrent measured at the nanowire detector due to absorption of light by the analyte. These miniature, portable and cost-effective spectrometers will be relevant in applications in homeland security, medical diagnostics, and optoelectronics. The student is expected to synthesize CdS/ZnS nanowires, characterize them using laser-optical microscope, study the waveguiding properties of nanowires, and direct the assembly of nanowires in microfluidic channels. The student will then assist in device fabrication and characterization of device properties including LEDs and photodiodes. No special skills required, except that highly-motivated students with general interest in nanomaterials/nanodevices.

Mechanical Engineering and Applied Mechanics

Jonathan Fiene

Integrating CAD/CAM/CAE into the MEAM curriculum

Through a partnership with the PACE (Partners for the Advancement of Collaborative Engineering Education) foundation, a new advanced computer-aided design, manufacturing, and analysis lab was opened within the School of Engineering in November 2007. With high-performance simulation software including NX5, Nastran, Adams, and Fluent, students now have the opportunity to utilize many of the same cutting-edge tools used in the automotive and aerospace industry. To fully leverage this amazing resource, a series of projects and experiments need to be designed and integrated into various courses within the Mechanical Engineering and Applied Mechanics department curriculum. Working closely with the lab director and other faculty within the department, this position will include the development, testing, and documentation of a sequence of modular labs, including advanced solid modeling, an introduction to computational fluid dynamics, a primer on stress/strain analysis using finite-element methods, and the use of Adams to perform simulations for dynamic systems. Prior experience with CAD/CAM/CAE tools would be highly useful, but not a strict requirement.

Katherine Kuchenbecker

Tactile Sensor and Actuator Design for Dexterous Space Gloves

The American space program is currently undergoing a radical shift in focus toward human exploration of the moon, Mars, and beyond. The success of such missions will require significant functional improvements to the suits that protect astronauts from these harsh environments, most notably in glove design. The wearer of a space suit must be able to perform dexterous finger movements and use common hand tools in as natural a manner as possible. To this effect NASA has conducted a number of open competitions to improve glove technology (see http://centennialchallenges.nasa.gov/). Haptics research has firmly established that tactile information (sensations such as pressure, skin stretch, slip, and high-frequency vibration) plays a critical role in the human ability to manipulate objects. Even the most advanced space gloves under consideration today fail to transmit these important channels of information to the wearer. For comparison, imagine trying to pick up a small object, such as a matchstick, while wearing a thick pair of winter gloves. Significant advancements will be required in the area of glove-based tactile feedback to give future space explorers the sensory information that is necessary to complete their unpredictable array of tasks. We seek a student who can take the lead role in designing and prototyping a system of contact sensors for the outside of a glove, along with an interior actuator array to relay these sensations to the wearer’s fingertips. Interested students should have some familiarity with mechanical design and electronic systems.

Visual Navigation Aid for Minimally Invasive Surgery

The technique of Minimally Invasive Surgery (MIS) employs long thin tools and an endoscopic camera that are inserted into the patient’s body through small incisions. By watching the video camera feed and manipulating these tools from the outside, surgeons are able to perform complex surgeries that would otherwise require large incisions. This operative approach can lead to dramatic reductions in both recovery time and patient infection, but unfortunately, MIS is a relatively difficult skill for surgeons to learn. The aspect of MIS that is most difficult for surgeons to understand is the spatial relationship between the images shown by the video camera and their hand motions. This challenge stems from the fact that the camera is often moved to different positions and orientations over the course of a surgery to improve the quality of its view. New and experienced surgeons both cite this hand-camera relationship as a dangerous and challenging situation that they must continuously learn to adapt to. We seek a student who can take a leading role in alleviating this problem by developing a user interface system that provides natural visual orientation cues. We anticipate that this feat can be accomplished by sensing the orientation of a standard MIS camera, feeding the image information through a host computer for processing, and then showing a spatially transformed version of the video to the surgeon in an intuitive interface. Applicants should have experience in at least one of the following areas, and they should be eager to learn about the others: C programming, electromechanical systems, and medical device design.

Fran Barg

Guatemala Health Initiative

The Guatemala Health Initiative is an on-going interdisciplinary partnership between the University of Pennsylvania and the Hospitalito Atitlan in Santiago Atitlan, Guatemala. Students and faculty are engaged in participatory research addressing significant health issues that face this highland Mayan community. Most recently, we have focused on the very high infant and maternal mortality rate in Santiago, collecting data from families, biomedical practitioners, indigenous midwives, and government health officials. During the summer, 2008, we would like to work with a student to analyze these data and prepare them for publication. Responsibilities include: coding and analyzing ethnographic data, synthesizing existing literature on infant and maternal mortality among indigenous populations and cataloguing new data as it comes in from the field. This is an excellent opportunity for a student who is interested in global health, medical anthropology, Central America, or women’s health issues. The student will be eligible to travel to Guatemala in subsequent years to participate in data collection. The student will work directly with faculty from anthropology, family medicine and nursing (midwifery). No pre-requisites.

Shared Decision Making in ADHD

Attention Deficit Hyperactivity Disorder (ADHD) is the most common mental health condition among youth in the United States. ADHD can negatively impact academic achievement, self-esteem, and interpersonal relationships. Despite the high prevalence of ADHD and the proven efficacy of medication and behavioral therapy, parents are often either reluctant to seek care or may not adhere to or agree with treatment after care is sought. Understanding how best to elicit and address families’ treatment-related preferences, goals, and needs may ultimately improve satisfaction with care, adherence, and outcomes. The objective of this study is to explore the factors influencing treatment decisions by parents and clinicians of children with ADHD and to describe the parents’ range of treatment preferences, goals, and needs to promote shared decision making (SDM) and tailor health care for children with this condition. We are seeking a student to work with our team this summer to interview parents who are referred to the study and to assist with data coding and analysis. The student will work with an interdisciplinary team including Dr. Alexander Fiks, a pediatrician at CHOP and Dr. Fran Barg, a medical anthropologist. We will train the student to conduct semi-structured interviews, to utilize qualitative data analysis software, and to code and analyze the data. No prerequisites.

Scott Halpern

Is it ethical to pay people to be living kidney donors?

As the gap between the supply of and demand for transplantable organs continues to grow, there is tremendous need for new ways to increase the organ supply. For kidneys and livers, one promising approach is living organ donation. Although many people have donated kidneys to family members and close friends, anonymous living donation has not lived up to expectations due to insufficient incentives for people to do it. One proposal to increase living donor rates is to provide financial incentives. However, paying people to donate a kidney raises several ethical concerns. Is paying people an undue inducement because it blinds them to the risks of donation? Is it an unjust inducement because it will be particularly influential among poorer people? This study aims to answer these questions by surveying a representative sample of Americans using an innovative questionnaire that assesses people’s willingness as the payments offered and risks to donating are systematically varied. The student’s roles in this project would include administering the written questionnaire in the Philadelphia courthouse as people are waiting to serve jury duty, entering the results into an electronic database, and reviewing the literature on the ethics of paying people to donate organs or take other risks. If interested, students would also be taught how to analyze the data and prepare a scientific manuscript. Authorship would be possible. There are no prerequisites other than an inquisitive mind.

Sylvia Rosas

Project 1

We are evaluating the role of vascular calcifications in CKD. There is increasing evidence that perhaps alterations of bone and mineral metabolism (calcium, phosphorus) are culprits. We will be starting a clinical trial in the near future to evaluate if different treatments may affect the progression of coronary calcification in CKD. Our recruitment goal is 50 patients. Subjects will have study visits every 4 weeks x 48 weeks.

Project 2

In this NIH sponsored study, we are evaluating if progression of coronary calcifications in a cohort of 112 renal transplant recipients. Our previous work has shown that coronary calcification is common and progresses after renal transplantation. We are interested in evaluating if oxidative stress is responsible for the progression of coronary calcifications. Oxidative stress is elevated in patients with CKD. The student does not need to have research experience, but needs to be hard-working and responsible. Students will learn clinical research skills related to nephrology and cardiovascular research. They will participate in the divisional lectures including our weekly lab and biostatistician meetings. Good communication skills are important for project 1 as there will be significant patient contact. All majors are welcome.

Microbiology

Jun Zhu

Quorum signal-regulated gene expression in Vibrio cholerae

Vibrio cholerae is a Gram-negative, facultatively anaerobic bacterial pathogen and is the causative agent of cholera. Recent in vitro studies reveal that quorum sensing systems, which exist in many bacteria to help them monitor their population densities and regulate various cellular functions, control V. cholerae virulence gene expression. To demonstrate the significance of the relationships between quorum sensing and pathogenesis in V. cholerae, we propose to study V. cholerae quorum signal regulated gene expression using in vitro (bacteria grown outside a host) and in vivo (bacteria grown in a host) models. We will determine the signal transduction pathways involving quorum sensing regulation and to examine the physiological functions of the quorum sensing regulation of these genes in an infant mouse model.

Jon Lindstrom

Development of a Specific Immunosuppressive Therapy for Myasthenia Gravis

Myasthenia gravis (MG) is caused by an antibody mediated autoimmune response to nicotinic acetylcholine receptors (AChRs) in skeletal muscles which causes muscular weakness by impairing neuromuscular transmission. Experimental autoimmune MG (EAMG) is induced by immunizing rats with AChRs purified from the electric organs of Torpedo californica. As a model for specific immunosuppressive therapy of MG, we have been treating rats with EAMG with bacterially-expressed human muscle AChR subunits given intraperitoneally. This diverts or suppresses the pathological autoimmune response, but we are trying to perfect this approach. These experiments will involve treating rats with only the cytoplasmic domains of AChR subunits. The idea is that antibodies formed in response to these peptides could bind only to intracellular parts of AChRs and thus would not be pathologically significant, although these peptides might stimulate T lymphocytes which could either increase or suppress the ongoing autoimmune response to AChRs. We will investigate whether giving these peptides in adjuvant to increase the antibody response increases or decreases their effectiveness in suppressing EAMG. These studies will involve preparing AChR subunit peptides, monitoring rats with EAMG for weakness, assaying their antibody titers to native AChRs and to the bacterially expressed subunit fragments, and measuring the amounts of AChRs in the rats.

Assaying the Function of Human Alpha 7 Neuronal Nicotinic Receptors in a Transfected Cell Line

Alpha 7 AChRs only properly assemble when human embryonic kidney cells are transfected both with alpha 7 subunits and with ric-3, a specific chaperone protein. The function of AChRs in this cell line can be assayed using an indicator which fluoresces when calcium ions enter the cell. Using this assay, it is easy to see activation of alpha 7 AChRs by acetylcholine or nicotine, but only when an additional allosteric activating drug PNU-120596 is added. We want to determine what inhibits the normal alpha 7 responses. We think that this inhibition might come from bovine serum albumin in the culture medium. If and when we can figure out how to routinely assay alpha 7 AChR function, we will assay it’s sensitivity to activation and desensitization by acetylcholine and nicotine and compare this with alpha 4 beta 2 and alpha 3 beta 4 AChR subtypes expressed in other transfected cell lines. We expect that alpha 7 will have low sensitivity to activation by nicotine but high sensitivity to desensitization by the continued presence of nicotine. These studies are of interest for understanding the relative effects of nicotine on major AChR subtypes found on neurons and on tumors.

Characterization of a Transfected Cell Line Which Expresses Human Alpha 4 Alpha 6 Beta 2 Beta 3 AChRs

Addiction to nicotine and Parkinson’s disease both involve neurons which release dopamine and have in their nerve endings AChRs which can promote dopamine release. An unusually complex subtype of AChR is involved at these endings. It is composed of alpha 4 alpha 6 beta 2 and beta 3 subunits. Alpha 4 and beta 2 can assemble into AChRs alone or in combination with beta 3, and alpha 6 and beta 2 can also assemble alone or with beta 3. We want to know the sensitivity to activation and desensitization of alpha 4 alpha 6 beta 2 beta 3 AChRs as compared to their related subtypes. In the continued presence of nicotine both alpha 4 beta 2 and alpha 6 beta 2 AChRs are assembled more efficiently, but alpha 4 beta 2 is more sensitive to upregulation in this way. In whole brains nicotine increases the amount of alpha 4 beta 2 AChRs but decreases the amount of alpha 6 AChRs. We think that this is because alpha 4 out competes alpha 6 for assembly with beta 2. We want to test in the cell line whether low concentrations of nicotine selectively upregulate alpha 4 and down regulate alpha 6 AChRs, and whether at high nicotine concentrations both subtypes or their complex subtype is upregulated.

Sarah Kagan

Narratives of Cancer Survivorship for People and Their Pets

Growing interest in companion animals has generated interest in their benefits to people with cancer though study of the connection between people and animals such dogs and cats has previously only established some health benefits to older adults. The proposed project seeks to establish a preliminary, substantive theoretical understanding of the interpretation and biographical influence of cancer survivorship for people who have pets when the person, the pet, or both are cancer survivors.. We are specifically interested in interpreting biographical influences, resources, and context on cancer survivorship when one or more pets are owned by people living with or after cancer. The primary aims of the project will be achieved through interpretation of biographies drawn from narratives of people who are being treated for cancer and those who own companion animals being treated for cancer as we look for the intersections between pet ownership and cancer survivorship. The contrast between perceptions of personal cancer survivorship and that of pets who are survivors undergirds the secondary aim to explore the biography of human-companion animal relationships within the phenomenon of survivorship. The research question for the project then is: what is the biography of cancer survivorship when the person, a pet, or both are cancer survivors? The novice student who participates in the project will join at the earliest phase and will participate in Institutional Review Board approval, start up phase with participant enrollment, and data collection with opportunity to develop a self-directed component for subsequent mentored analysis and publication.

Identity and Biography Among Older Women Cancer Survivors

Interactions among age, gender, and cancer are poorly understood as they influence identity and biography for women who are menopausal and surviving rare cancers. The proposed project seeks to establish a preliminary, substantive theoretical understanding of the interpretation and biographical influence of cancer survivorship for women who are over 50 years of age (50+ women) and survivors of head and neck or gynecologic cancers. We are specifically interested in elucidating and interpreting biographical influences and resources related to age, gender, and the site of cancer. The primary aim of the project will be achieved through interpretation of biographies drawn from narratives of women who were diagnosed at age 50 or later with a head and neck or gynecologic cancer, the contrast between which we are using to highlight public and private identity in cancer survivorship. The research question for the project then is: what is nature of identity in the biographies of 50+ women surviving cancer? The novice student who participates in the project will join at the earliest phase and will participate in Institutional Review Board approval, start up phase with interdisciplinary team negotiations and participant enrollment, and data collection with opportunity to develop a self-directed component for subsequent mentored analysis and publication.

Terri Lipman

The Philadelphia Pediatric Diabetes Registry

Type 1 diabetes mellitus s the second most common chronic disease in childhood and affects 1 in 500 school aged children. The incidence of Type 2 diabetes in children is rapidly increasing, especially among African-American and Hispanic children, is strongly associated with obesity and is a severe public health problem. This project is a continuation of the Philadelphia Pediatric Diabetes Registry that has been ongoing since 1985; one of only 3 such registries in the country. In addition to data on type 1 diabetes, these data will include some of the only incidence data on type 2 diabetes in children. The student will obtain institutional review board approval as required. Once permission to review charts is obtained, the student will abstract charts for standard WHO diabetes registry data. Charts meeting the following criteria will be reviewed: (1) newly diagnosed diabetes; (2) ages 0- 19 years; (3) residing in the City of Philadelphia at the time of diagnosis; and (4) diagnosed after January 1, 2000. To capture children with diabetes who have not been admitted to the hospital, students will also review the outpatient hospital records meeting the same criteria. To clarify the typololgy of diabetes, additional information to be abstracted from the records will include: age, sex, family history of diabetes, maternal diabetes during pregnancy, race/ethnicity, birth weight, presenting symptoms or circumstances of the diagnosis, treatment with insulin or oral agents. The student will enter the data into an ACCESS database. Determining the epidemiology of pediatric diabetes is the mandatory first step enabling investigators to apply for funding for effective screening, intervention and therapeutic strategies for children affected with this serious chroni