Biology Commons^™

Genetic Explanations: Sense And Nonsense, Garland E. Allen

Biology Faculty Research

Book review of Sheldon Krimsky; Jeremy Gruber (Editors). Genetic Explanations: Sense and Nonsense. xi + 368 pp., index. Cambridge, Mass.: Harvard University Press, 2013. $45 (cloth).

Joint Phenotypes, Evolutionary Conflict And The Fundamental Theorem Of Natural Selection, David C. Queller

Biology Faculty Research

Multiple organisms can sometimes affect a common phenotype. For example, the portion of a leaf eaten by an insect is a joint phenotype of the plant and insect and the amount of food obtained by an offspring can be a joint trait with its mother. Here, I describe the evolution of joint phenotypes in quantitative genetic terms. A joint phenotype for multiple species evolves as the sum of additive genetic variances in each species, weighted by the selection on each species. Selective conflict between the interactants occurs when selection takes opposite signs on the joint phenotype. The mean fitness of …

Fruiting Bodies Of The Social Amoeba Dictyostelium Discoideum Increase Spore Transport By Drosophila, Jeff Smith, David C. Queller, Joan E. Strassmann

Biology Faculty Research

Background: Many microbial phenotypes are the product of cooperative interactions among cells, but their putative fitness benefits are often not well understood. In the cellular slime mold Dictyostelium discoideum , unicellular amoebae aggregate when starved and form multicellular fruiting bodies in which stress-resistant spores are held aloft by dead stalk cells. Fruiting bodies are thought to be adaptations for dispersing spores to new feeding sites, but this has not been directly tested. Here we experimentally test whether fruiting bodies increase the rate at which spores are acquired by passing invertebrates.
Results: Drosophila melanogaster accumulate spores on their surfaces more quickly …

A Course-Based Research Experience: How Benefits Change With Increased Investment In Instructional Time, Christopher Shaffer, Consuleo Alvarez, April Bednarski, David Dunbar, Anya Goodman, Catherine Reinke, Anne Rosenwald, Michael Wolyniak, Cheryl Bailey, Daron Barnard, Christopher Bazinet, Dale Beach, James Bedard, Satish Bhalla, John Braverman, Martin Burg, Vidya Chandrasekaran, Hui-Min Chung, Kari Clase, Randall Dejong, Justin Diangelo, Chunguang Du, Todd Echdahl, Heather Eisler, Julia Emerson, Amy Frary, Donald Frohlich, Yuying Gosser, Shubha Govind, Adam Haberman, Amy Hark, Charles Hauser, Arlene Hoogewerf, Laura Hoopes, Carina Howell, Diana Johnson, Christopher Jones, Lisa Kadlec, Marian Kaehler, Catherine Silver-Key, Adam Kleinschmit, Nighat Kokan, Olga Kopp, Gary Kuleck, Judith Leatherman, Jane Lopilato, Christy Mackinnon, Juan Carlos Martinez-Cruzado, Gerard Mcneil, Stephanie Mel, Hemlata Mistry, Alexis Nagengast, Paul Overvoorde, Don Paetkau, Susan Parrish, Celeste Peterson, Mary Preuss, Laura Reed, Dennis Revie, Srebrenka Robic, Jennifer Roecklein-Canfield, Michael Rubin, Kenneth Saville, Stephanie Schroeder, Karim Sharif, Mary Shaw, Gary Skuse, Christopher Smith, Mary Smith, Sheryl Smith, Eric Spana, Mary Spratt, Aparna Sreenivasan, Joyce Stamm, Paul Szauter, Jeffrey Thompson, Matthew Wawersik, James Youngblom, Leming Zhou, Elaine Mardis, Jeremy Buhler, Wilson Leung, David Lopatto, Sarah C.R. Elgin

Biology Faculty Research

There is widespread agreement that science, technology, engineering, and mathematics programs should provide undergraduates with research experience. Practical issues and limited resources, however, make this a challenge. We have developed a bioinformatics project that provides a course-based research experience for students at a diverse group of schools and offers the opportunity to tailor this experience to local curriculum and institution-specific student needs. We assessed both attitude and knowledge gains, looking for insights into how students respond given this wide range of curricular and institutional variables. While different approaches all appear to result in learning gains, we find that a significant …

Hp1a: A Structural Chromosomal Protein Regulating Transcription, Joel Eissenberg, Sarah C.R. Elgin

Biology Faculty Research

Heterochromatin protein 1 (HP1a in Drosophila) is a conserved eukaryotic chromosomal protein that is prominently associated with pericentric heterochromatin and mediates the concomitant gene silencing. Mechanistic studies implicate HP1 family proteins as 'hub proteins,' able to interact with a variety of chromosomal proteins through the chromo-shadow domain (CSD), as well as to recognize key histone modification sites [primarily histone H3 di/trimethyl Lys9 (H3K9me2/3)] through the chromodomain (CD). Consequently, HP1 has many important roles in chromatin architecture and impacts both gene expression and gene silencing, utilizing a variety of mechanisms. Clearly, HP1 function is altered by context, and potentially by post-translational …

A Broadly Implementable Research Course In Phage Discovery And Genomics For First-Year Undergraduate Students, Tuajuanda Jordan, Sandra Burnett, Susan Carson, Steven Caruso, Kari Clase, Randall Dejong, John Dennehy, Dee Denver, David Dunbar, Sarah C.R. Elgin, Ann Findley, Chris Gissendanner, Urszula Golebiewska, Nancy Guild, Grant Hartzog, Wendy Grillo, Gail Hollowell, Lee Hughes, Allison Johnson, Rodney King, Lynn Lewis, Wei Li, Frank Rosenzweig, Michael Rubin, Margaret Saha, James Sandoz, Christopher Shaffer, Barbara Taylor, Louise Temple, Edwin Vazquez, Vassie Ware, Lucia Barker, Kevin Bradley, Deborah Jacobs-Sera, Welkin Pope, Daniel Russell, Steven Cresawn, David Lopatto, Cherly Bailey, Graham Hatfull

Biology Faculty Research

Engaging large numbers of undergraduates in authentic scientific discovery is desirable but difficult to achieve. We have developed a general model in which faculty and teaching assistants from diverse academic institutions are trained to teach a research course for first-year undergraduate students focused on bacteriophage discovery and genomics. The course is situated within a broader scientific context aimed at understanding viral diversity, such that faculty and students are collaborators with established researchers in the field. The Howard Hughes Medical Institute (HHMI) Science Education Alliance Phage Hunters Advancing Genomics and Evolutionary Science (SEA-PHAGES) course has been widely implemented and has been …

A Distinct Type Of Heterochromatin At The Telomeric Region Of The Drosophila Melanogaster Y Chromosome, Ruth Nan, Sidney Wang, Maria Accardo, Monica F. Sentmanat, Patrizio Dimitri, Sarah C.R. Elgin

Biology Faculty Research

Heterochromatin assembly and its associated phenotype, position effect variegation (PEV), provide an informative system to study chromatin structure and genome packaging. In the fruit fly Drosophila melanogaster, the Y chromosome is entirely heterochromatic in all cell types except the male germline; as such, Y chromosome dosage is a potent modifier of PEV. However, neither Y heterochromatin composition, nor its assembly, has been carefully studied. Here, we report the mapping and characterization of eight reporter lines that show male-specific PEV. In all eight cases, the reporter insertion sites lie in the telomeric transposon array (HeT-A and TART-B2 homologous repeats) of the …

Tribute To Tinbergen: The Place Of Animal Behavior In Biology, Joan E. Strassmann

Biology Faculty Research

Tinbergen is famous for emphasizing behavioral fieldwork and experimentation under natural circumstances, for founding the field of ethology, for getting a Nobel Prize, and for mentoring Richard Dawkins. He is known for dividing behavior studies into physiology, development, natural selection, and evolutionary history. In the decades since Tinbergen was active, some of the best research in animal behavior fuses Tinbergen's questions, connecting genes to behavioral phenotypes, for example. Behavior is the most synthetic of the life sciences, because observing the actions of an organism can tell us what all those physical and physiological traits are for. Insights from behavior tell …

Origins Of The Classical Gene Concept, 1900–1950: Genetics, Mechanistic, Philosophy, And The Capitalization Of Agriculture, Garland E. Allen

Biology Faculty Research

In the period of “classical genetics” (roughly 1915–1950), the common view of the gene was mechanistic—that is, genes were seen as individual, atomistic units, as material components of the chromosomes. Although it was recognized early on that genes could interact and influence each other’s expression, they were still regarded as individually functioning units, much like the chemists’ atoms or molecules. Although geneticists in particular knew the story was more complex, the atomistic gene remained the central view for a variety of reasons. It fit the growing philosophy of mechanistic materialism in the life sciences, as biologists tried to make their …

Arabidopsis Msl10 Has A Regulated Cell Death Signaling Activity That Is Separable From Its Mechanosensitive Ion Channel Activity, Kira M. Veley, Grigory Maksaev, Elizabeth M. Frick, Emma January, Sarah C. Kloepper, Elizabeth S. Haswell

Biology Faculty Research

Members of the MscS superfamily of mechanosensitive ion channels function as osmotic safety valves, releasing osmolytes under increased membrane tension. MscS homologs exhibit diverse topology and domain structure, and it has been proposed that the more complex members of the family might have novel regulatory mechanisms or molecular functions. Here, we present a study of MscS-Like (MSL)10 from Arabidopsis thaliana that supports these ideas. High-level expression of MSL10-GFP in Arabidopsis induced small stature, hydrogen peroxide accumulation, ectopic cell death, and reactive oxygen species- and cell death-associated gene expression. Phosphomimetic mutations in the MSL10 N-terminal domain prevented these phenotypes. The phosphorylation …

A Central Support System Can Facilitate Implementation And Sustainability Of A Classroom-Based Undergraduate Research Experience (Cure) In Genomics, Jeremy Buhler, Elaine Mardis, Wilson Leung, Christopher Shaffer, Jennifer Threlfall, Sarah C.R. Elgin, David Lopatto, Charles Hauser, Christopher Jones, Don Paetkau, Vidya Chandrasekaran, David Dunbar, Christy Mackinnon, Joyce Stamm, Consuelo Alvarez, Daron Barnard, James Bedard, April Bednarski, Satish Bhalla, John Braverman, Martin Burg, Hui-Min Chung, Randall Dejong, Justin Diangelo, Chunguang Du, Todd Eckdahl, Julia Emerson, Amy Frary, Donald Frohlich, Anya Goodman, Yuying Gosser, Shubha Govind, Adam Haberman, Amy Hark, Arlene Hoogewerf, Diana Johnson, Lisa Kadlec, Marian Kaehler, Catherine Silver-Key, Nighat Kokan, Olga Kopp, Gary Kuleck, Jane Lopilato, Juan Martinez-Cruzado, Gerard Mcneil, Stephanie Mel, Alexis Nagengast, Paul Overvoorde, Susan Parrish, Mary Preuss, Laura Reed, Gloria Regisford, Dennis Revie, Srebrenka Robic, Jennifer Roecklien-Canfield, Anne Rosenwald, Michael Rubin, Kenneth Saville, Stephanie Schroeder, Karim Sharif, Mary Shaw, Gary Skuse, Christopher Smith, Mary Smith, Sheryl Smith, Eric Spana, Mary Spratt, Aparna Sreenivasan, Jeffrey Thompson, Matthew Wawersik, Michael Wolyniak, James Youngblom, Leming Zhou

Biology Faculty Research

In their 2012 report, the President's Council of Advisors on Science and Technology advocated "replacing standard science laboratory courses with discovery-based research courses"-a challenging proposition that presents practical and pedagogical difficulties. In this paper, we describe our collective experiences working with the Genomics Education Partnership, a nationwide faculty consortium that aims to provide undergraduates with a research experience in genomics through a scheduled course (a classroom-based undergraduate research experience, or CURE). We examine the common barriers encountered in implementing a CURE, program elements of most value to faculty, ways in which a shared core support system can help, and the …

The Genetic Architecture And Evolution Of Brain Cortical Folding In A Pedigreed Primate Population, Elizabeth Grace Atkinson

Arts & Sciences Graduate Student Theses and Dissertations

Elevated neurological faculty, related to the dramatic increase in brain volume, is a hallmark of the primates. Cognitive capacity, the processing power and speed of the brain, is directly related to the number of neurons in the cerebral cortex and the connectivity network underlying information processing in the brain. Increased cortical folding (gyrification) allows for more neurons to be contained within the volume of the braincase and the arrangement of folds and ridges across the cerebral cortex is an indication of the underlying neural network connecting regions. The goal of this dissertation is to develop a better understanding of the …

A Seasonal, Density-Dependent Model For The Management Of An Invasive Weed, Esther Shyu, Eleanor A. Pardini, Tiffany M. Knight, Hal Caswell

Biology Faculty Research

The population effects of harvest depend on complex interactions between density dependence, seasonality, stage structure, and management timing. Here we present a periodic nonlinear matrix population model that incorporates seasonal density dependence with stage-selective and seasonally selective harvest. To this model, we apply newly developed perturbation analyses to determine how population densities respond to changes in harvest and demographic parameters. We use the model to examine the effects of popular control strategies and demographic perturbations on the invasive weed garlic mustard (Alliaria petiolata). We find that seasonality is a major factor in harvest outcomes, because population dynamics may …

Mechanisms For Regulation Of Plant Kinesins, Anindya Ganguly, Ram Dixit

Biology Faculty Research

Throughout the eukaryotic world, kinesins serve as molecular motors for the directional transport of cellular cargo along microtubule tracks. Plants contain a large number of kinesins that have conserved as well as specialized functions. These functions depend on mechanisms that regulate when, where and what kinesins transport. In this review, we highlight recent studies that have revealed conserved modes of regulation between plant kinesins and their non-photosynthetic counterparts. These findings lay the groundwork for understanding how plant kinesins are differentially engaged in various cellular processes that underlie plant growth and development.

Microtubule Severing At Crossover Sites By Katanin Generates Ordered Cortical Microtubule Arrays In Arabidopsis, Quan Zhang, Erica Fishel, Tyler Bertroche, Ram Dixit

Biology Faculty Research

Highlights

• Severing primarily depolymerizes the overlying CMT at crossover sites
• Severing probability increases nonlinearly with crossover time
• Katanin localizes to crossover sites and is required for severing
• Loss of katanin activity prevents the formation of coaligned CMT arrays

Summary
The noncentrosomal cortical microtubules (CMTs) of land plants form highly ordered parallel arrays that mediate cell morphogenesis by orienting cellulose deposition [1, 2 and 3]. Since new CMTs initiate from dispersed cortical sites at random orientations [4], parallel array organization is hypothesized to require selective pruning of CMTs that are not in the dominant orientation. Severing of CMTs at crossover sites …

Mscs-Like Mechanosensitive Channels In Plants And Microbes, Margaret E. Wilson, Grigory Maksaev, Elizabeth S. Haswell

Biology Faculty Research

The challenge of osmotic stress is something all living organisms must face as a result of environmental dynamics. Over the past three decades, innovative research and cooperation across disciplines have irrefutably established that cells utilize mechanically gated ion channels to release osmolytes and prevent cell lysis during hypoosmotic stress. Early electrophysiological analysis of the inner membrane of Escherichia coli identified the presence of three distinct mechanosensitive activities. The subsequent discoveries of the genes responsible for two of these activities, the mechanosensitive channels of large (MscL) and small (MscS) conductance, led to the identification of two diverse families of mechanosensitive channels. …

The Uropathogenic Escherichia Coli Effector Ybcl Modulates The Innate Immune Response In The Urinary Tract, Megan Elizabeth Lau

Arts & Sciences Graduate Student Theses and Dissertations

Uropathogenic Escherichia coli (UPEC) are the primary etiology of urinary tract infections (UTIs), one of the most common bacterial infections afflicting the human population. While UPEC cause disease throughout the urinary tract, bladder infection, or cystitis, is most prevalent. A key aspect of UPEC pathogenesis in the bladder is the modulation of the host inflammatory response. At acute time points, UPEC delay the arrival of immune cells, such as neutrophils, to the bladder. The lack of neutrophils in the bladder lumen enables UPEC to replicate freely in the urine and invade the bladder epithelium, a requirement for bacterial persistence, in …

The Natural Variants Of The Streptococcus Nad+-Glycohydrolase Spn Modulate Divergent Host Cell Signaling Pathways And Death, Sukantha Chandrasekaran

Arts & Sciences Graduate Student Theses and Dissertations

Streptococcus pyogenes has an arsenal of virulence factors that promote its ability to cause a broad range of diseases and fight host defenses. One of these factors is the S. pyogenes NAD+-glycohydrolase (SPN), which is secreted from the bacterial cell and translocated into the host cell cytosol where it contributes to cell death. Every strain examined to date has SPN and recent studies suggest that SPN is continuing to evolve diverging into two variants that correlate with tissue tropism, one of which lacks the signature NADase activity. SPN's roles in both cytotoxicity and niche selection are unknown. To gain insight …

Type 1 Diabetes And The Male Reproductive Axis, Erica Schoeller

Arts & Sciences Graduate Student Theses and Dissertations

Glucose regulation is important in both spermatogenesis as well as mature sperm function. The impact of diabetes on sperm function is becoming increasingly clear, though much work is still needed to elucidate the mechanism by which diabetes impairs spermatogenesis. Diabetes causes disruptions in the hypothalamic pituitary gonadal (HPG) axis, the regulatory system that controls reproduction. The HPG axis functions by secreting GnRH pulses from the hypothalamus, which bind to receptors on the pituitary and cause secretion of follicle stimulating hormone and luteinizing hormone, which then bind to receptors in the testes and facilitate spermatogenesis. Type 1 diabetes can severely impact …

Dysfunctional Gene Regulation Of The Meiotic Program In An Interspecific Yeast Hybrid, Devjanee Swain Lenz

Arts & Sciences Graduate Student Theses and Dissertations

Speciation, the evolutionary process by which species arise, is a fundamental biological concept. One of the major goals of evolutionary genetics is to understand the genetic basis of reproductive isolation (RI), a collection of barriers that prevents two species from forming viable or fertile hybrids. Given the lack of viable or fertile hybrid progeny, identifying genes that impact RI as well as their functions has been difficult. Thus we lack a view of the total genetic contribution to RI. Recently the budding yeast Saccharomyces has served as an evolutionary model, as abundant sequence, expression, and phenotypic data exist for the …

Development Of Polarizable Force Field Models For Transition Metal Ions, Jin Yu Xiang

Arts & Sciences Graduate Student Theses and Dissertations

This dissertation focuses on the development of polarizable molecular mechanics (MM) force field models for the third-row transition metal (TM) ions. These TM ions perform important structural and chemical functions in a wide range of organic and biological environments because of the unique properties of the 3d orbitals. Being able study these systems in silico can provide a tremendous amount of information that is difficult to obtain through experiments. However, the standard treatment of ions in traditional MM models has shown to be insufficient for describing the d-shell electronic effects. In this work, empirical models for TM electronic effects are …

Quantification Of Conformational Heterogeneity And Its Role In Protein Aggregation And Unfolding, Nicholas J. Lyle

Arts & Sciences Graduate Student Theses and Dissertations

Proteins can exhibit significant conformational heterogeneity either under denaturing conditions or in aqueous solutions. The latter is true for a class of proteins whose sequences predispose them to form heterogeneous ensembles of conformations. Characterization of conformational heterogeneity in a protein ensemble requires the quantification of the amplitudes of spontaneous fluctuations in conjunction with information regarding coarse grain measures that report on the average sizes, shapes, and densities. This often demands multiplexed experimental approaches whose readouts are interpreted or annotated using ensembles drawn from atomistic or coarse grain computational simulations. Efforts to characterize conformational heterogeneity contribute directly to our understanding of …

Post-Translational Regulation Of Fas-Mediated Pparα Activation, Anne Patricia Louise Jensen-Urstad

Arts & Sciences Graduate Student Theses and Dissertations

The liver is a central organ to whole-body metabolism and mediates many of the adaptive responses to changes in nutrient availability, such that the appropriate energy sources are used and blood glucose levels maintained, whether directly after a meal or after a twelve-hour fast. The adaptive responses to fasting in liver are largely mediated by the nuclear receptor peroxisome proliferator-activated receptor α, or PPARα. PPARα can be activated by a de novo synthesized lipid ligand—16:0/18:1- glycerophosphocholine (16:0/18:1-GPC)—the synthesis of which is dependent on fatty acid synthase (FAS), but little is known about the regulation of this pathway. My thesis focused …

Heterochromatin Protein 1a (Hp1a) Partner Specificity Is Determined By Critical Amino Acids In The Chromo Shadow Domain And C-Terminal Extension, Deanna Lynn Mendez, Rebecca Mandt, Sarah C.R. Elgin

Biology Faculty Research

Drosophila melanogaster Heterochromatin Protein 1a (HP1a) is an essential protein critical for heterochromatin assembly and regulation. Its chromo shadow domain (CSD) homodimerizes, a requirement for binding protein partners that contain a PXVXL motif. How does HP1a select among its many different PXVXL-containing partners? HP1a binds tightly to Heterochromatin Protein 2 (HP2), but weakly to PIWI. We investigated differences in homodimerization and the impact of the C-terminal extension (CTE) by contrasting HP1a to its paralogue, HP1b. HP1a and HP1b differ in the dimerization interface, with HP1a having an Arg at position 188 rather than Glu. We find that while this substitution …

A Force Of Nature: Molecular Mechanisms Of Mechanoperception In Plants, Gabriele B. Monshausen, Elizabeth S. Haswell

Biology Faculty Research

The ability to sense and respond to a wide variety of mechanical stimuli-gravity, touch, osmotic pressure, or the resistance of the cell wall-is a critical feature of every plant cell, whether or not it is specialized for mechanotransduction. Mechanoperceptive events are an essential part of plant life, required for normal growth and development at the cell, tissue, and whole-plant level and for the proper response to an array of biotic and abiotic stresses. One current challenge for plant mechanobiologists is to link these physiological responses to specific mechanoreceptors and signal transduction pathways. Here, we describe recent progress in the identification …

The Rate And Effects Of Spontaneous Mutation On Fitness Traits In The Social Amoeba, Dictyostelium Discoideum, David W. Hall, Sara Fox, Jennie J. Kuzdzal-Fick, Joan E. Strassmann, David C. Queller

Biology Faculty Research

We performed a mutation accumulation (MA) experiment in the social amoeba Dictyostelium discoideum to estimate the rate and distribution of effects of spontaneous mutations affecting eight putative fitness traits. We found that the per-generation mutation rate for most fitness components is 0.0019 mutations per haploid genome per generation or larger. This rate is an order of magnitude higher than estimates for fitness components in the unicellular eukaryote Saccharomyces cerevisiae, even though the base-pair substitution rate is two orders of magnitude lower. The high rate of fitness-altering mutations observed in this species may be partially explained by a large mutational target …

Role Of Nucleation In Cortical Microtubule Array Organization: Variations On A Theme, Erica A. Fishel, Ram Dixit

Biology Faculty Research

The interphase cortical microtubules (CMTs) of plant cells form strikingly ordered arrays in the absence of a dedicated microtubule-organizing center. Considerable research effort has focused on activities such as bundling and severing that occur after CMT nucleation and are thought to be important for generating and maintaining ordered arrays. In this review, we focus on how nucleation affects CMT array organization. The bulk of CMTs are initiated from γ-tubulin-containing nucleation complexes localized to the lateral walls of pre-existing CMTs. These CMTs grow either at an acute angle or parallel to the pre-existing CMT. Although the impact of microtubule-dependent nucleation is …

Plant Cytoskeleton: Della Connects Gibberellins To Microtubules, Ram Dixit

Biology Faculty Research

A new study reveals that DELLA proteins directly interact with the prefoldin complex, thus regulating tubulin subunit availability in a gibberellin-dependent manner. This finding provides a mechanistic link between the growth-promoting plant hormone gibberellin and cortical microtubule organization.

Targeting Heterochromatin Formation To Transposable Elements In Drosophila: Potential Roles Of The Pirna System, Monica F. Sentmanat, Sh Wang, Sarah C.R. Elgin

Biology Faculty Research

Successful heterochromatin formation is critical for genome stability in eukaryotes, both to maintain structures needed for mitosis and meiosis and to silence potentially harmful transposable elements. Conversely, inappropriate heterochromatin assembly can lead to inappropriate silencing and other deleterious effects. Hence targeting heterochromatin assembly to appropriate regions of the genome is of utmost importance. Here we focus on heterochromatin assembly in Drosophila melanogaster, the model organism in which variegation, or cell-to-cell variable gene expression resulting from heterochromatin formation, was first described. In particular, we review the potential role of transposable elements as genetic determinants of the chromatin state and examine how …

Urine Trouble: A Molecular And Anatomical Examination Of Bladder Pain, Lara Wiley Crock

Arts & Sciences Graduate Student Theses and Dissertations

Interstitial cystitis or painful bladder syndrome (IC/PBS) is a chronic pain syndrome affecting 3-6% of women in the US. Some evidence suggests urothelial injury may cause some cases of IC/PBS. To examine how urothelial injury modulates bladder pain, three injury models were used: Infection with uropathogenic Escherichia coli (UPEC, inflammatory), Protamine sulfate (PS, non-inflammatory chemical), and lipopolysaccharide (LPS, non-infectious and inflammatory) treatment. Surprisingly, injury with PS decreased, while UPEC alone increased the pain response to bladder distention. These data suggest that changes in the urothelium may modulate some forms of IC/PBS. However, in most cases, patients with IC/PBS have no …