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Mary M. Allen Go
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Mary M. Allen - Microbial physiology, biochemistry and ultrastructure (email Professor Allen)
Research Group - Summer 1998 Studies on the effects of environmental change on the physiology and biochemistry of cyanobacteria are being carried out in collaboration with undergraduate students. Structured granules (cyanophycin granules) have been isolated and purified from cyanobacteria and studies are underway on the physiology and control of their formation. Cyanophycin granules accumulate in cells which are nutrient starved or grown under conditions of protein synthesis inhibition. Fine structural analysis (negatively stained, sectioned, and freeze-fractured preparations) of both purified granules and those developing in cells has been done, radioisotopic and heavy isotope incorporation experiments are in progress with analysis by liquid scintillation counting, GC/MS, and NMR. A protease hydrolyzing them is being analyzed and purified. One and two dimensional electrophoresis and immunoblotting have been used to characterize proteins from cells grown under different conditions. Uptake and transport studies involved in nitrogen uptake and limitation are planned in conjunction with analysis of enzymes and control mechanisms for nitrate metabolism and photosynthesis. Nitrogen metabolism is being studied by 15N incorporation followed by analysis with NMR spectrometry.
electron micrograph of cyanbacterium Recent Student Projects: 1) Metabolic control in a heterotrophic cyanobacterium using enzyme assays, purification, and kinetics, radioisotopic incorporation, thin layer and column chromatography. 2) Protease isolation, purification and kinetics using enzyme assays, isotope incorporation, and protein purification techniques. 3) Analysis of cyanophycin granule formation from protein breakdown studied by 15N labeling,isotope incorporation, cell fractionation, chemical, NMR and GC/MS analysis. 4) Analysis of heat and pH shock proteins by pulse-labeling, gel electrophoresis and immunoblotting. Return to Biological Sciences Faculty List
Barbara S. Beltz - Developmental Neurobiology My laboratory is primarily concerned with four goals: to understand (1) the development of chemical transmitter systems in neurons; (2) the ontogenesis of behavior; and (3) the physiological and behavioral actions of amines and peptides (substances that are contained in neurons and are known to be biologically active); 4) the morphogenic effects of transmitters during development. In studying the developmental acquisition of transmitter, we are particularly interested in neurons that show "plasticity," or change in transmitter properties between developmental and adult lives. The differentiation of a cell often commits it to a particular fate for the rest of its life. In contrast, some neurons are able to alter their morphological, physiological, or biochemical properties after their initial differentiation. We have been examining the timing of acquisition of amine and peptide transmitters in the nervous system of the lobster during embryonic and larval development. Particular neurons, by virtue of their prematurely large size or transient immunocytochemical staining properties, appear to play interesting developmental roles. We would like to define the functions of such cells, and in particular study the period in these neurons' lives when their biochemical properties are changing. We are also attempting to manipulate the developmental fates for specific neurons by use of trophic factors and toxins. We ultimately hope to correlate the acquisition of transmitter in identified neurons with the acquisition of particular behaviors during development, to define the physiological actions of amines and peptides involved in those behaviors, and to understand how transmitters may play a role as developmental "architects" during embryogenesis.
Student Projects: A variety of projects are available to students, depending upon their personal interests. We utilize a number of anatomical (immunocytochemistry; anterograde and retrograde dye filling of neurons; electron microscopy; autoradiography), physiological (extracellular and intracellular recording from lobster neurons), and biochemical (radioimmunoassay) methods. The most popular projects have been the analysis and mapping of neural antigens using immunocytochemical methods in embryonic, larval, and adult lobsters, in order to define the timing of acquisition of the antigen. Some students have also proposed behavioral and physiological experiments. They have looked at the behavioral effects of administering particular transmitters at different developmental stages, or have assayed electrophysiologically for effects of those substances on other neurons or on peripheral targets. Return to Biological Sciences Faculty List
Joanne Berger-Sweeney - Behavioral Neurobiology My laboratory is concerned with understanding the role the basal forebrain structures play in the development of learning and memory. Basal forebrain neurons provide the primary cholinergic projections to the cerebral cortex and hippocampus in the rodent. In adulthood, loss of the cholinergic projections to cortex results in severe relational memory deficits. During development, these projections appear to influence the morphogenesis of the particular layers of the cerebral cortex. However, it is not known, how or if, these morphogenic changes in the cortex lead to alterations in cognition in adulthood. We are using as a model system, mice that receive basal forebrain lesions on postnatal day one and are allowed to grow to adulthood to test the effects of early cholinergic deafferentation on the performance of cognitive tasks in adult mice. Currently, the primary focus of the laboratory is to determine: 1) whether loss of cholinergic projections to the cortex during development results in cognitive deficits in adulthood, 2) whether these cognitive deficits could be correlated with neurochemical changes in the cortex, 3) Whether these cognitive deficits could be attenuated by pharmacological interventions, and 4) whether these deficits could be correlated with electrophysiological changes in the cortex. We ultimately hope to gain a better understanding of the mechanisms involved in cortical development and cognitive functions. Student Projects: A variety of projects are available to students, depending upon their personal interests. We are currently utilizing a number of behavioral, pharmacological and neurochemical techniques. Specifically, mice and rats are run in water maze tasks and their spatial learning patterns are analyzed with and without various drug interventions. Following the behavioral experiments, cholinergic enzymatic activity is being assayed in cortical tissue. In the near future, we will be setting up stations to conduct extracellular recordings in behaving animals. Return to Biological Sciences Faculty List
Beverly Blazar - Epstein-Barr Virus Immunology Epstein-Barr Virus (EBV) infection enables B lymphocytes to grow continuously in cell culture. The cellular alterations and molecular basis of this transformation, however, are not understood. EBV is carried latently by cells in the majority of Burkitt's lymphomas, but the relationship of virus to the oncogenic process has not yet been determined. Studies by our laboratory and others suggest that EBV infection causes an autostimulatory cycle in B lymphocytes because the virus transformed cells produce factor sto which they respond by proliferating. The ongoing research in the laboratory is designed to gain information about the role of growth enhancing factors in the growth of immortalized B lymphocytes. We have found that these autostimulatory factors have Interleukin activity in immune assays. Our studies will determine whether the production of and/or response to autostimulatory factors is universal to all normal and neoplastic B cells or is only a property of EBV transformed lymphocytes, evaluate the role of EBV in inducing this phenomenon, compare the activities of this factor by molecular cloning to other identified factors, characterize one molecule isolated from cell culture supernatants by our laboratory, and determine the molecular events that affect autostimulation in immortalized B lymphocytes. Student Projects: 1) Cell culture projects evaluating EBV-carrying cells for the production of growth factors and for the presence of a membrane bound form of these factors; 2) biochemical studies of factors produced by EBV-carrying cells; 3) functional assays to determine expression of growth factors during the cell cycle. Return to Biological Sciences Faculty List
Emily Buchholtz - Paleobiology, Paleoneurology (mail Professor Buchholtz) My interests include a wide range of topics in comparative vertebrate anatomy and paleontology. In recent years both my field collection and museum/lab work has centered on swimming vertebrates and the history of their transitions from terrestrial to aquatic environments. Although seals, whales, seacows, and ichthyosaurs have all returned to the sea, each transition started with a different terrestrial anatomy and took a different path to an obligate marine lifestyle. I have used both paleoneurological and osteological approaches to my work. My paleoneurological projects have used the analysis of the neural canal to reconstruct gross anatomy of the postcranial nervous system and to study neural supply to the limbs. My comparative osteological work documents vertebral column anatomy and swimming style in living vertebrates, and applies the observed relationships to the study of extinct vertebrates whose swimming style cannot be observed.
During my recent sabbatical semester in the spring of 1999, I studied the postcranial anatomy of Jurassic ichthyosaurs. Previous projects include swimming styles in living whales, posture in dinosaurs, forelimb use in theropod dinosaurs, preference of limb use in the swimming patterns of seals and walruses, and flight ability in birds. Student projects: Recent projects include: Regional vertebral variation and swimming style in the ichthyosaur Baptanodon Ontogenetic variation in spinal cord anatomy in living and fossil hominids. Functional implications of neural canal antomy in Primates, Paleoecology of the Early Cretaceous Muddy Formation of the Big Horn Basin, Wyoming, Chondrichthyans of the Muddy Formation, Big Horn Basin, Wyoming, Limb Use and Disuse in Ratites. Return to Biological Sciences Faculty List
John S. Cameron - Comparative Vertebrate Physiology (email Professor Cameron) My research is concerned with the cardiovascular physiology of ectothermic ('cold-blooded') animals| in particular, I am interested in the ionic mechanisms that promote tolerance of low-oxygen and low temperature conditions in vertebrates. Within the past few years, my students and I have been using glass microelectrodes to investigate the cellular electrophysiology of isolated cardiac muscle tissue and individual heart cells. We are particularly interested in the cellular mechanisms underlying tolerance to hypoxia and hypothermia in 'lower' verte- brates. Many fish and amphibians, for example, can withstand prolonged exposure to environmental conditions of cold and low oxygen that would prove lethal to mammals, or even to other fish. The difference between tolerant species and those sensitive to hypoxia and hypothermia may reflect, in part, alterations in the activity of specific ion channels in the cell membrane of essential organs. Tolerant tissues might respond, for example, with a reduction in the density and/or rate of activation of such channels, thus reducing membrane permeability and compensating for decreased ATP-dependent ion pumping capacity in the face of low oxygen or cold environments. Student Projects: In the coming year, I expect that there will be numerous opportunities for a student to initiate projects in line with her own interests. We are currently using intracellular and single-channel, patch-clamp recording techniques to characterize the activity of individual ion channels (ie., K+, Ca++, etc.) on the surface of living heart muscle cells. Cardiac muscle cells are isolated from species thought to be highly tolerant of enviromental extremes, or from individuals acclimated at a variety of different temperatures. One hypothesis on which we expect to focus in the coming year is that cardiac ATP-sensitive K+ channels are activated during metabolically stressful conditions in a manner that provides increased tolerance of low oxygen. Return to Biological Sciences Faculty List
Mary Downey Coyne - Endocrinology (Biochemistry, Electrophysiology) (email Professor Coyne) Project Description My primary interest is endocrinology. In the past I have concentrated on investigating the response of calcium channels to hormonal stimulation. Recently I have also initiated studies on temperature regulation in women. More particularly, we are investigating the effects of the sex hormones released during the menstrual cycle on the diurnal pattern of core body temperature and heat loss via the skin. Because of the two types of projects, investigations in both cellular and systemic physiology are available in the lab. Menstrual Cycle and Temperature Regulation - When core temperature is perturbed by either exercise, or heat or cold stress, appropriate heat loss or conservation mechanisms are activated. However, these systems respond differently in women depending on the phase of the menstrual cycle. In some situations, the variation in core body temperature makes acute adaptation to environmental extremes less effective. For example, in the luteal phase of the cycle, core body temperature must be higher before sweating is initiated during exercise. Women have a different problem in adapting to cold due to their greater surface area in relation to mass, which increases the rate of heat loss. This is demonstrated by the fact that women have colder skin and core temperatures than men in similar conditions despite exercising at similar intensities. This implies that cold tolerance is reduced in women. Additionally, reports suggest that the female reproductive hormones alter the 24-hour rhythm of core body temperature producing greater heat retention in the second half of the menstrual cycle versus the first. While most evidence supports the idea that these monthly and daily changes in core body temperature are regulated by adjusting the brain temperature "set-point", it is also possible that the reproductive hormones act locally at the cutaneous blood vessels to modify skin blood flow and thereby adjust heat loss or gain through the skin. We propose to study how reproductive hormones affect the daily pattern of core body temperature and heat loss via the cutaneous vasculature at several points in the menstrual cycle. This project involves working with human subjects and sophisticated mathematical analysis of the resulting data. Calcium Channels - We have also have a cooperative research project with John Cameron, Ph.D. and Judith Gwathmey, DVM to study the differential response of fish hearts to hypoxia. In our lab we are using the perforated patch clamp technique to study the calcium currents in ventricular myocytes. Calcium currents are the sum of the action of the total population of calcium channels in the membrane of a single cell. We plan on continuing this cooperative project by looking at the response of calcium currents to hypoxia and by correlating these changes with the form of the action potential (Cameron's lab) and ventricular contraction (Gwathmey's lab). We will be using two species of fish, one that is very sensitive to oxygen deprivation (trout) and one relatively insensitive (goldfish). Student Projects: Menstrual Cycle and Temperature Regulation - Investigated skin temperatures as indicators of peripheral vasodilation during different phases of the menstrual cycle. The major thrust of the research in the lab will be continuation of a physiological study with the U.S. Army Institute of Environmental Medicine on thermoregulation in women. The work will involve interacting with human subjects, coordinating all aspects of the research and analyzing the large sets of data. Calcium Channels - Investigated effects of temperature on calcium channels in myocytes from trout hearts. Used the perforated patch clamp techniques to monitor calcium currents in single cells. A paper describing this work has been submitted, i.e. "Calcium currents in rainbow trout, Oncorhynchus mykiss, using the perforated patch clamp, and their response to different temperatures in vitro." An additional paper, done in conjuction with Cameron & Gwarthmey, on the "Effect of temperature and calcium availability on the physiology of ventricular myocardium from rainbow trout, Oncorhynchus mykiss" has also been submitted. Return to Biological Sciences Faculty List
My principle research interest is photosynthesis. Currently I am interested in purifying and characterizing enzymes of the dark reactions of photosynthesis. I have also recently initiated some cytological and biochemical investigations into the nature of the association of the actin cytoskeleton and the chloroplast. Student Projects: 1. Purification of phosphoriboisomerase 2. The actin cytoskeleton in corn bundle sheath cells Return to Biological Sciences Faculty List
Marianne V. Moore - Aquatic Ecology Global climate warming models predict that surface water temperatures of New England lakes may rise as much as 40C by mid-next century. Summer heat waves, however, occur now and are predicted to increase in frequency with climatic warming. Such events of elevated water temperature (>250C) affect feeding rates of fish and grazing rates of zooplankton. The outcome of these altered species interactions on water quality (e.g. water clarity) is unknown. Likewise, interactive effects of warmer temperatures and sublethal toxicant concentrations on zooplankton behavior and demography are poorly understood. This information is critical for evaluating current water quality standards which were established using results of zooplankton reproduction tests conducted at cooler temperatures. Experiments designed to assess the interactive effects of these 2 abiotic stressors (warm temperatures and a toxicant) on zooplankton reproduction, survival, and behavior will involve a combination of field and laboratory work. Student projects: 1) assessing effects of maximum summer and winter temperatures predicted from global warming models on predator-prey interactions in pelagic lake communities, 2) assessing interactive effects of warmer water temperatures and sublethal toxicant concentrations on zooplankton behavior and reproduction. Return to Biological Sciences Faculty List
T. Kaye Peterman - Plant Molecular and Developmental Biology My research interests are focused on the molecular genetics and developmental biology of the higher plant Arabidopsis thaliana. Arabidopsis, a member of the mustard family, possesses a number of characteristics which make it an excellent model system for the study of plant biology. Some of these are: small plant size, short generation time, prolific seed production and a small simply organized genome.
The specific long term goal of my research is to elucidate the physiological functions of lipoxygenase (LOX) in higher plants, using a combination of molecular biological, genetic and biochemical approaches. While the physiological roles of LOX in plants have not been well-defined, it is clear that the enzyme is involved in a number of essential processes, including growth and development and the response to biotic and abiotic stresses. Furthermore, the primary products of the LOX reaction, fatty acid hydroperoxides, are precursors to regulatory molecules in both plant and animal cells. Jasmonates, the best characterized of these in plants, are phytohormones which have been shown to effect a number of physiological processes including the regulation of gene expression. Jasmonates have also been implicated as signal transduction molecules in the response of plants to pathogen attack and wounding. The plants in which LOX has been studied to date have large numbers of LOX genes and isozymes that have complicated analysis of it's physiological function. In order to utilize a simpler system I have initiated a molecular physiological study of LOX in the model crucifer, Arabidopsis thaliana. The work of my laboratory and that of my collaborators, Drs. Erin Bell and John Mullet, indicates that Arabidopsis contains two LOX genes and is in fact much simpler than other plants in this regard. In my laboratory we have isolated and characterized cDNA and genomic clones for the LOX1 gene of Arabidopsis. We have demonstrated that this gene is induced in response to bacterial pathogen attack and by the phytohormones, methyl jasmonate and abscisic acid. In addition we have shown that LOX activity and LOX1 expression peak during seed germination, consistent with a role in early development. Finally, to facilitate analysis of LOX protein levels, a LOX1-maltose binding fusion protein was produced in E. coli and used to produce polyclonal antibodies. I now have in hand all of the molecular tools required to analyze and manipulate the expression of the LOX1 gene in Arabidopsis. I am presently using these tools to study the role of the LOX1 gene in the defense response to bacterial pathogens and in seed germination. I am also exploring the use of the LOX1 induction by ABA and methyl jasmonate as a system for genetic analysis of phytohormone action in plants. Return to Biological Sciences Faculty List
Nicholas L. Rodenhouse - Terrestrial Ecology Research being conducted by myself and Wellesley students focuses on the foraging behavior and reproductive ecology of birds. We are particularly interested in how weather influences parental care and reproductive success of House Finches that nest in the gothic street lamps of Wellesely College campus. This readily accessible population is ideal for testing hypotheses about how climatic changes, such as those predicted due to the "greenhouse effect," might influence bird populations. In conjunction with our experimental work in the field, we are developing simulation models that use behavioral and reproductive data to predict changes in bird populations. Student projects: Student projects could be carried out in the field or laboratory. Potential field projects include: 1) testing hypotheses about avian parental care in relation to various environmental factors; 2) investigating bird foraging patterns by documenting and/or manipulating availability of food; or 3) growth studies of nestling birds in relation to weather conditions. Laboratory studies might include modelling the reproductive success of a House Finch population. Past student projects have focused on a wide variety of study systems in addition to avian ecology. These included: 1) testing hypotheses about plant allocation of biomass to leaves, stems, and roots, 2) modelling the effect of density dependence on the probability of population extinction, 3) studying dispersal of chromium from lead chromate deposits northwest of Lake Waban, 4) examining temperature dependence of the predatory activity of beetles dwelling in leaf litter, 5) testing whether pheromones were the basis of sexual selection in flour beetles, 6) examining the process of self-thinning in a plant population, and 7) modeling the resilience of coral populations stressed by frequent storm damage or pollution. No doubt, there is a testable idea among your interests. Return to Biological Sciences Faculty List
Dennis M. Smith - Histology, Cytology, Electron Microscopy The general area of my research interest is the structure and function of the mammalian lung, with emphasis on alveolar structure and function. The alveoli of the lung are the tiny, thin walled sacs where the exchange of gases actually occurs. My research focuses on several aspects of these alveoli, including the connective tissue which supports them, and the epithelial cells which cover their surfaces. We are currently studying the effects of the drug propranolol on the cells and other structures of the lung alveoli. This drug is widely prescribed as Inderal, and our studies indicate that it may have a deleterious effect on alveolar structure. We are looking at this effect in fetal, young adult and aging rats. The methods used in my laboratory include electron microscopy, which demonstrates structural features of the lung, various biochemical determinations, and cell culture. Student Projects: Previous honors students have worked on various aspects of lung structural-functional relationships. Two students utilized electron microscopy to study the reactions of adult type II cells to pilocarpine, an agent which mimics the action of the parasympathetic nervous system. Two other students localized autonomic binding sites in the lung by autoradiography. Other students have utilized electron microscopy in various projects, including one who studied the effects of fibroblastic growth factor on myocardial infarcts. Current projects in the lab focus on the effects of propranolol on adult and fetal lung, and on possible mediators of the injury response. Return to Biological Sciences Faculty List
Andrew C. Webb - Developmental and Molecular Biology Over the past few years, my research effort has been directed towards the molecular cloning of human genes that are of biomedical interest. First, in collaboration with labs at MIT and Tufts New England Medical Center, we were the first to obtain a cDNA clone for the monocyte-derived immunomodulator known as interleukin-1 (IL-1). IL-1 mediates a vast array of host responses to infection and disease, including fever, initiation of the immune reaction and the complex metabolic changes collectively referred to as the "acute phase response." In addition to direct anti-tumor activity, IL-1 has been demonstrated to stimulate bone-marrow reconstitution following both radiation and chemotherapy. Over-production of IL-1 is associated with arthritis. Our present work is focussed on understanding the molecular mechanisms that activate IL-1 genes. Isolation of the genomic sequence for human IL-1 from chromosome 2 has allowed us to embark on an experimental evaluation of IL-1 gene control. This project is supported by funds from NIH and is carried out in collaboration with labs at MGH East in Charlestown, MIT and the Joint Center for Radiation Therapy in Boston. Largely as a result of the efforts of past Wellesley students (BioSci 316, 350, 370), we were able to characterize a cDNA clone for another important monocyte product; an inhibitor of urokinase. Urokinase-type plasminogen activator (uPA) belongs to the group of enzymes known as serine proteases that bring about tissue destruction at sites of both inflammation and tumor growth, as well as being intimately involved in the process of blood clotting. These potent enzymes are controlled by specific inhibitors which block their action. The cDNA clone isolated at Wellesley was for a specific uPA inhibitor referred to as PAI-2 synthesized primarily by human monocytes. Work on isolation of the DNA sequences on chromosome 18 that code for and control the transcription of the PAI-2 gene has just been completed. Future experiments will focus on the factors that regulate human PAI-2 gene expression. The PAI-2 protein has therapeutic utility in the control of fibrinolysis in thromboembolic disease and the control of tumor cell metastasis. Newly initiated work with the Brigham and Women's Hospital Respiratory Division is directed at elucidating a molecular mechanism for activation of proteases (eg. cathepsins) by being macrophage in response to cigarette smoking. The large-scale production of recombinant human IL-1 and PAI-2 proteins for use as potential therapeutic agents is being performed in insect cells using the baculovirus expression system. A project to evaluate the efficacy of the human PAI-2 protein to prevent or reduce the metastasis of melanoma in a mouse model was recently funded by a Brachman Hoffman Grant. This work will be carried out entirely at Wellesley over the next two years. Mutated forms of IL-1 that bind to their receptors as effectively as the wild-type molecule, but elicit no cellular responses are being evaluated both as IL-1 antagonists, and also as reagents to determine the molecular mechanisms involved in trans-membrane signal transduction. Much of this latter IL-1 work is being carried out in collaboration with the MIT and Charlestown labs. Student Projects: * regulation of IL-1 and PAI-2 gene expression in human cell lines * purification of recombinant human IL-1 and PAI-2 using the baculovirus expression system * isolation and characterization of cathepsin gene regulatory elements Return to Biological Sciences Faculty List
Jennifer Hood-DeGrenier - Yeast genetics and cell biology, nuclear transport and cell cycle regulation (e-mail Professor Hood-DeGrenier) The principle feature of the eukaryotic
cell is the compartmentalization of its various life processes into
specialized organelles. This spatial segregation creates a powerful
potential for regulation that is not available to prokaryotes. My primary
research interest lies in understanding the mechanisms by which proteins
are targeted to discrete subcellular locations and the functional consequences
of this targeting. One focus of my lab is the process by which proteins
are transported between the nucleus and the cytoplasm through specialized
channels called nuclear pore complexes. I am also interested in how
regulated nuclear transport can be used to control the cell division
cycle. Current research in my lab seeks to understand how the localization
of a particular cell cycle regulatory protein to several distinct subcellular
sites impacts its ability to perform multiple functions related to cell
division. Student Projects: Return to Biological Sciences Faculty List
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