FALL 2010 ASA GRAY BIOLOGICAL SOCIETY SEMINAR SERIES
September 13th, 2010
“Estrogen Signaling and Regulation of Primordial Follicle Formation”
Melissa Pepling, Ph.D.
Department of Biology, Syracuse University
In mammals, the pool of primordial follicles present at birth represents the total population of germ cells available to a female during her entire reproductive life. Oocytes develop as clusters of interconnected cells called germ cell cysts in embryonic mouse ovaries. During the perinatal period, oocyte cysts break apart and granulosa cells surround individual oocytes to form primordial follicles. As the cysts break down, some oocytes in each cyst die with only a third of the initial number surviving. Mechanisms regulating cyst breakdown and follicle assembly to establish the pool of primordial follicles are not well understood. In addition, it is unclear why some oocytes die during cyst breakdown. Recent work from several groups suggests that estrogens may inhibit cyst breakdown. Treatment of neonatal mice with natural or synthetic estrogens results in abnormal multiple oocyte follicles in adult ovaries. Neonatal estrogen treatment inhibits cyst breakdown suggesting multiple oocyte follicles are cysts that did not break apart. Estrogen works through nuclear hormone receptors, estrogen receptor (ER) α and ERβ. To understand how estrogen signals in neonatal ovaries, three approaches were taken. First, we examined the expression of ERs in neonatal mouse ovaries and detected ERα in granulosa cells and ERβ in oocyte nuclei. Second, ovaries in organ culture were treated with ER selective agonists. We found that ERα and ERβ agonists inhibited cyst breakdown, suggesting that estrogen can signal through either receptor in the developing ovary. Third, we examined oocyte development in mice lacking either ERα or ERβ. Surprisingly, cyst breakdown and follicle assembly was normal in both mutant strains suggesting that one receptor could compensate for the other. Cyst breakdown was only slightly altered ER mutants lacking both receptors implying that another receptor may be involved. Supporting this, estradiol modified so that it can only exert effects at the membrane, was able to inhibit cyst breakdown, implying that estrogen can also function through a novel membrane bound estrogen receptor. Understanding how oocytes develop will give insight into premature ovarian failure, reproductive lifespan, menopause and ovarian cancer and contribute to potential treatments of female infertility.
October 25, 2010
“Many variations on a few themes: A broad look at structure and development of insect scales and bristles.”
H. Ghiradella, Ph.D.
Professor of Biology, The University at Albany
The arthropod integument is noted for its outgrowths, in particular, its hairs, bristles and scales. These start as hollow cuticular projections templated on projections (microvilli or filopodia for hairs and larger projections for scales and bristles) from parent epidermal cells. Bristles and scales in particular are usually noted for their complex architecture, study of whose development yields insights into more general mechanisms of cellular pattern formation.
We will consider what is known of these developmental mechanisms, in particular those that appear to be guided by two cellular systems, the actin cytoskeleton and the smooth endoplasmic reticulum (SER), which appear multitalented to the extreme in their ability to orchestrate very different structures and functions in what would seem to be otherwise unremarkable cells.
November 8, 2010
“Polysaccharide-Based Strategies for Improving the Therapeutic Efficacy of Disease-Modifying Anti-Rheumatic Drugs”
Rebecca A. Bader, Ph.D.
Biomedical & Chemical Engineering, Syracuse Biomaterials Institute, Syracuse University
Historically, rheumatoid arthritis (RA) has been treated with gold salts that have anti-rheumatic properties, such as auranofin, immunosuppressants that are typically used following organ transplantation, including cyclosporine A, or with cytotoxic cancer therapeutics that have immunosuppressive side effects, particularly methotrexate. These so called disease-modifying anti-rheumatic drugs (DMARDs) have severe, potentially life threatening, consequences due to non-specific targeting and impaired immune function. In recent years, paradigms have shifted towards combining toxic drugs with molecular vehicles intended to promote delivery exclusively to the diseased region, thereby increasing efficacy and reducing side effects. To further enhance this specificity, the carrier systems are often combined with targeting moieties such as antibodies, small peptides, and natural ligands. This talk will describe our approaches towards improving the delivery of both hydrophilic and hydrophobic DMARDs to the inflamed joint tissue. We use polysaccharide-based materials for direct conjugation or encapsulation of common drugs used in the treatment of rheumatoid arthritis. Recent studies have focused on the use of polysialic acid and hyaluronic acid to improve circulatory stability and/or actively target cells within the diseased region. This talk will also highlight in vitro methods used to assess the efficacy of drug delivery systems. In sum, the work described provides insight into how drug delivery technology can be used to improve the lives of those that suffer from rheumatoid arthritis.
November 22, 2010
“Secondary Bacterial Infections as the Cause of Death from Influenza”
Dennis Metzger, Ph.D.
Professor and Theobald Smith Alumni Chair Director
Center for Immunology and Microbial Disease, Albany Medical College
Dr. Metzger's research program concentrates on examining new approaches for immune protection in the respiratory tract. The mechanisms responsible for viral-bacterial synergy in the lung are of particular interest. It is well known that secondary bacterial infection often follows pulmonary virus infection and is a major cause of severe disease, especially during influenza pandemics in humans, including the 1918 Spanish flu pandemic that killed over 50 million people worldwide. Combined infection with a highly virulent influenza virus and a bacterial strain such as pneumococcus can create a “perfect storm” that leads to very high rates of mortality. However, the reasons for this are only poorly understood. Dr. Metzger's laboratory has now demonstrated that pulmonary interferon (IFN)-gamma produced during T cell responses to influenza infection inhibits scavenger receptor expression by alveolar macrophages and hence, bacterial clearance from the lung. This suppression of phagocytosis then leads to enhanced susceptibility to secondary bacterial infection, which can be prevented by IFN-gamma neutralization following influenza infection Thus, the hypothesis of the work is that induction of an adaptive immune response against an intracellular pathogen in the lung (virus) results in significant impairment of innate alveolar macrophage-mediated protection against extracellular pathogens (bacteria). Current work is focused on characterizing functional changes in alveolar macrophages induced by influenza virus infection and determining the mechanisms responsible for the inhibition of alveolar macrophage-mediated bacterial clearance. The ultimate goal is to develop novel, safe and efficacious strategies for biodefense against potential pandemic threats.
December 6, 2010
“Smart material substrates for cell culture”
James Henderson, Ph.D.
Department of Biomedical and Chemical Engineering, Syracuse University
Living cells are remarkably complex, dynamic, and versatile systems, but the material substrates currently used to culture them are not. Although properties of the material substrate, such as surface geometry and stiffness, can direct cell lineage specification, cell growth kinetics, cell orientation, cell migration, and cell traction, the polymeric materials commonly used in cell culture, such as polystyrene, offer attached cells only a 2D surface of unchanging properties. This physical stasis of current cell culture materials severely limits our ability to control cell-material interactions during cell culture and, therefore, our ability to advance understanding of fundamental cell processes. This seminar will present current work in which we are developing “active” cell culture technologies that allow dynamic control of cell-material interactions. The potential for these approaches to control cell-material interactions during 2D cell culture for biological and bioengineering research and applications will be discussed.
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"Without any doubt in my mind, one of the only reasons that I was able to complete my education and successfully enter my current position as a Ph.D. candidate in genetics was due to the constant support and guidance that I received at UC." "Without any doubt in my mind, one of the only reasons that I was able to complete my education and successfully enter my current position as a Ph.D. candidate in genetics was due to the constant support and guidance that I received at UC."
Susan A. Zullo '92
National Center for Human Genome Research
National Center for Human Genome Research