Life Sciences Commons^™

Engineering Mesothelin-Binding Proteins As Targeted Cancer Diagnostics And Therapeutics, Allison Rita Sirois

Doctoral Dissertations

Cancer is a significant global health concern; and traditional therapies, including chemotherapeutics, are often simultaneously toxic yet ineffective. There is a critical need to develop targeted cancer therapeutics which specifically inhibit molecules or molecular pathways essential for tumor growth and maintenance. Furthermore, a targeted therapy is only effective when a patient's tumor expresses the molecular target; therefore, companion diagnostics, including molecular imaging agents, are a necessary counterpart of targeted therapies. Mesothelin (MSLN) is a cell surface protein overexpressed in numerous cancers, including triple-negative breast, pancreatic, ovarian, liver, and lung, with limited expression in normal tissues. Aberrant MSLN expression promotes tumor …

Origin Of Gene Specificity In The Nitrogen-Fixing Symbiosis, Christina Marie Stonoha-Arther

Doctoral Dissertations

Many legumes form a symbiosis with nitrogen-fixing bacteria found in the soil. This relationship is beneficial to both the plant and the bacteria; the plant receives nitrogen that is otherwise limited, and the bacteria receive fixed carbon. Upon sensing the bacteria, the plant forms a new organ (the nodule) where the bacteria are housed within the cells. Many genes are required for the proper formation and function of nodules; this dissertation is broadly focused on how genes required for nitrogen-fixing symbiosis are co-opted from other cellular processes and how they are specialized for symbiosis. Protein trafficking from the plant to …

Physiology Of A Basal Vertebrate, The Sea Lamprey (Petromyzon Marinus): Osmoregulation And Corticosteroid Action, Ciaran A. S. Shaughnessy

Doctoral Dissertations

Lamprey represent the most basal living example of a vertebrate animal which regulates its internal fluid and ion homeostasis. This phylogenetic position among vertebrates makes lamprey an important model organism for understanding the basal state, and thus the evolution, of physiological systems such as the mechanisms of osmo- and ionoregulation and the endocrine factors controlling them. Sea lamprey (Petromyzon marinus) are an anadromous fish, migrating from freshwater (FW) to seawater (SW) as juveniles, then returning back upstream as mature adults to spawn. Surviving this transition from a solute-poor FW environment to a solute-concentrated SW environment requires many changes …

Improved Molecular Diagnostics For Soil-Transmitted Helminths, Nils Pilotte

Doctoral Dissertations

Current World Health Organization recommendations for the diagnosis of soil-transmitted helminths (STH) rely on antiquated microscopy-based techniques that lack both diagnostic sensitivity and specificity. While sufficient for providing rough estimates of infection frequency and intensity within high prevalence settings, these techniques lack the capacity to effectively estimate infection levels following successful intervention efforts, as worm burdens decline and community prevalences decrease. Furthermore, an expanding body of evidence is suggesting that microscopy-based misdiagnosis of infection is likely a larger concern then previously believed. As such, with an increase in programmatic support for transmission interruption and an escalating belief in the possibility …

Tpr-Containing Proteins Control Protein Organization And Homeostasis For The Endoplasmic Reticulum, Jill Bradley-Graham

Doctoral Dissertations

The endoplasmic reticulum (ER) is a complex, multifunctional organelle comprised of a continuous membrane and lumen that is organized into several functional regions. It plays various roles including protein translocation, folding, quality control, secretion, calcium signaling, and lipid biogenesis. Cellular protein homeostasis is maintained by a complicated chaperone network, and the largest functional family within this network consists of proteins containing tetratricopeptide repeats (TPRs). TPRs are well-studied structural motifs that mediate intermolecular protein-protein interactions, supporting interactions with a wide range of ligands or substrates. Nine TPR-containing proteins have been shown to localize to the ER and control protein organization and …

De-Coding The Impact Of Evolved Changes In Gene Expression And Cellular Phenotype On Primate Evolution, Trisha Zintel

Doctoral Dissertations

The goal of the dissertation work outlined here was to investigate the influence of proximal processes contributing to evolutionary differences in phenotypes among primate species. There are numerous previous comparative analyses of gene expression between primate brain regions. However, primate brain tissue samples are relatively rare, and my results have contributed to the pre-existing data on more well-studied primates (i.e. humans, chimpanzees, macaques, marmosets) as well as produced information on more rarely-studied primates (i.e. patas monkey, siamang, spider monkey). Additionally, the primary visual cortex has not previously been as extensively studied at the level of gene expression as other brain …

Improving Growth And Survival Of Cultured Yellow Lampmussel (Lampsilis Cariosa) For Restoring Populations, Virginia Martell

Masters Theses

In North America 72% of freshwater mussel species are endangered, threatened, or of special concern due to factors such as habitat loss and degradation, biological invasion, and land use change. Propagation of freshwater mussels has been considered a necessary conservation strategy for population restoration where threats have been mitigated but small population sizes limit population viability. Yellow lampmussel is a species of freshwater mussel that is endangered, threatened, or imperiled throughout its range; therefore, I evaluated laboratory techniques (probiotic supplements and secondary rearing designs) to improve culture of yellow lampmussel for population restoration. Several aquaculture facilities commonly use probiotics; thus, …

Engineering Of An Antibody-Conjugated Nanogel Platform For Targeted Drug Delivery To T Lymphocytes, Mine Canakci

Doctoral Dissertations

In an ideal chemotherapy, cytotoxic drugs travel through the bloodstream, reach cells all over the body and preferentially kill abnormal cells. Yet, the hydrophilic or lipophilic property of the small-molecule drugs affects their ability to reach cells from the bloodstream. So, only a small portion of the drug reaches to the diseased tissue. A selective cell killing approach for cancer therapy gained momentum after the realization that cancer cells carry unique set of molecular markers on their cell surface. The development of antibody drug conjugates (ADC) revolutionized the targeted approach for drug delivery. ADCs are composed of cytotoxic agents covalently …

Characterizing The Interaction Between Non-Pathogenic Fusarium Oxysporum And Arabidopsis Thaliana To Determine Beneficial Effects Conferred To The Model Plant Host, Kathryn Isabelle Vescio

Masters Theses

Fusarium oxysporum (Fo) is a soil-borne fungal pathogen that causes vascular wilt disease on a broad range of plants, including agricultural crops and the model plant Arabidopsis thaliana. There are non-pathogenic members of the Fo species complex that confer defense benefits against other pathogens to the host plant, however alteration to the host’s physiology through interaction with one of these strains, Fo47, have not been described. In this study, we aimed to establish the Fo47-A. thaliana interaction and determine if Fo47 reduces disease severity of a pathogenic Fo isolate, Fo5176. Additionally, we sought to use bioinformatics to mine …

Investigating The Genetic Basis Of And Plasticity In Ecologically Relevant Phenotypes In African Cichlids, Dina Navon

Doctoral Dissertations

Understanding the generation of phenotypic variation by linking it to genetic variation has long been a focus of evolutionary biology; this framework has successfully been implemented in a variety of studies across the tree of life^1,2. However, our understanding of the phenotype remains incomplete until we account for a myriad of interactions that influence the genotype-phenotype map, including interactions between traits (TxT), interactions between genes and the environment (GxE), as well as the ways in which various types of interactions are nested within and build upon one another (e.g., (TxT)xG). My dissertation aims to contribute to filling this …

Reimagining The One-Shot - A Student-Centered Approach For Introducing First-Year Students To The Library, Alissa Link

New England Library Instruction Group

This session explored how a traditional library instruction session was adapted to give students a richer and more interactive learning experience leading to the expansion of a collaboration between an introductory biology class and the library. The session detailed the adaption of an existing lesson plan, creation of an asynchronous scavenger hunt, and addition of a student-centered, hands-on assignment.

To encourage self-driven learning, the library instruction session was redesigned to include hands-on, in-class components and an asynchronous scavenger hunt. Both changes were enthusiastically received by the course faculty.

The end result of the adapted curriculum for the introductory biology course …

Visual Attention In Jumping Spiders, Margaret Bruce

Masters Theses

The different ways that animals extract and analyze visual information from their environment is of interest to sensory ecologists. Jumping spiders, well-known for visually guided mating and hunting behavior, are an interesting model for the study of visual attention because they quickly and efficiently integrate information from eight eyes with a small brain. Stimuli in front of the spider are examined by two functionally and morphologically distinct pairs of forward-facing eyes. The principal eyes discern fine details and have small retinas and thus a small visual field. However, their position at the back of moveable tubes within the cephalothorax expands …

2019 Patterns Around Us Handout, Benjamin Davidovitch, Narayanan Menon, Wayne Kermenski, Jennifer Welborn

Patterns Around Us

This is a FREE two-day program designed for Middle and High School General Science, Biology, Physics, Technology/Engineering teachers. It is funded by the National Science Foundation.Space is limited, so apply soon! Some limited funding is available for overnight stay.

“Science may be described as the attempt to give good accounts of the patterns in nature. The result of scientific investigation is an understanding of natural processes.... Overall, the key criterion of science is that it provides a clear, rational, and succinct account of a pattern in nature....” Massachusetts State Frameworks for Science and Technology.

Participants will explore the processes of …

Microtubule Plus-Ends Act As Physical Signaling Hubs To Activate Rhoa During Cytokinesis, Vikash Verma, Thomas J. Maresca

Biology Department Faculty Publication Series

Microtubules (MTs) are essential for cleavage furrow positioning during cytokinesis, but the mechanisms by which MT-derived signals spatially define regions of cortical contractility are unresolved. In this study cytokinesis regulators visualized in Drosophila melanogaster (Dm) cells were found to localize to and track MT plus-ends during cytokinesis. The RhoA GEF Pebble (Dm ECT2) did not evidently tip-track, but rather localized rapidly to cortical sites contacted by MT plus-tips, resulting in RhoA activation and enrichment of myosin-regulatory light chain. The MT plus-end localization of centralspindlin was compromised following EB1 depletion, which resulted in a higher incidence of cytokinesis …

Cardiovascular Disease Risk And Menopause: Effects Of Cardiorespiratory Fitness, Exercise, And Follicle Stimulating Hormone, Corinna Serviente

Doctoral Dissertations

Menopause is associated with adverse changes in cardiovascular disease risk factors. A reduction in estrogens is most commonly associated with changing cardiovascular disease risk; however, recent observations suggest that the increase in follicle stimulating hormone that accompanies menopause may also influence risk, potentially through its influence on lipid levels. The changes in cardiovascular disease risk factors may adversely affect endothelial cell function, a pre-clinical marker for cardiovascular disease. Whether cardiorespiratory fitness is protective of endothelial health in this population, thereby mitigating the changes in risk that accompany menopause, is unclear. This dissertation evaluated differences in endothelial health and endothelial responses …

An Integrative Approach To Understanding Morphological Novelties: Anatomy, Development, Genetics, And Evolution Of An Extreme Craniofacial Trait In East African Cichlids, Moira R. Conith

Doctoral Dissertations

Phenotypic novelties are an important but poorly understood category of morphological diversity that are often associated with elevated rates of diversification and/or ecological success. The aim of this dissertation is to explore a phenotypic novelty at many levels to contribute to our understanding of how these unique traits can arise (e.g., genetically, developmentally, and evolutionarily) as well as their ecological consequences (e.g., trait function). The extreme snout of the Lake Malawi cichlid fish Labeotropheus is used as a case study. The first chapter establishes the Labeotropheus snout as a model of phenotypic novelty by characterizing the gross morphology, genetic architecture, …

Plants, Parasites, And Pollinators: The Effects Of Medicinal Pollens On A Common Gut Parasite In Bumble Bees, George Locascio

Masters Theses

Declines in several pollinator species are due to a variety of factors, including pathogens. Incorporating pollinator-friendly plant species into wild and agricultural habitats could reduce the stress of pathogens if food sources act medicinally against pathogens. Previous research demonstrated one domesticated sunflower cultivar (Helianthus annuus) can dramatically reduce a gut pathogen (Crithidia bombi) of the common eastern bumble bee, Bombus impatiens. To ascertain the breadth of this medicinal trait, we tested whether pollen from several H. annuus cultivars and four relatives could also reduce C. bombi infections in B. impatiens. We also investigated whether …

Characterization Of She1 Spindle Role Using Ceullular, Biochemical, And Biophysical Methods, Yili Zhu

Doctoral Dissertations

During development, metaphase spindles undergo large movement and/or rotation to determine the cell division axis. While it has been shown that spindle translocation is achieved by astral microtubules pulling and/or pushing the cortex, how metaphase spindle stability is maintained during translocation remains not fully understood. In budding yeast, our lab has previously proposed a model for spindle orientation wherein the mitotic spindle protein She1 promotes spindle translocation across the bud neck by polarizing cortical dynein pulling activity on the astral microtubules. Intriguingly, She1 exhibits dominant spindle localization throughout the cell cycle. However, whether She1 has any additional role on the …

Canonical Notch Signaling Positively Regulates Mir-155 Transcription In A Nfκb-Dependent Manner, Joe Torres

Doctoral Dissertations

MicroRNA-155 (miR-155) is an important pro-inflammatory molecule that controls immune responses in both physiological and pathological settings. Although miR-155 is well studied, little is known about its transcriptional regulation in T cells. We sought to further understand the mechanisms by which miR-155 transcription is induced following T cell activation. We found that miR-155 transcription is dependent on the activity of the Notch and NFkB signaling pathways. It was determined that the canonical Notch signaling pathway was involved in this regulation and that it was dependent upon the activation of NFkB. Additional work confirmed that both NFkB and Notch1 directly bind …

Microenvironment Regulates Fusion Of Breast Cancer Cells, Peiran Zhu

Masters Theses

Fusion of cancer cells has been observed in tumors for more than a century and is thought to contribute to tumor development and drug resistance. The low frequency of cell fusion events and the instability of fused cells have hindered our ability to understand the molecular mechanisms that govern cell fusion. We have developed a patterned gel system that can isolate cell fusion events and we demonstrate that several breast cancer cell lines can fuse into multinucleated giant cells in vitro, and the initiation and longevity of fused cells can be regulated solely by biophysical factors. Dynamically tuning the adhesive …

Transposable Elements In Fusarium Oxysporum & Growth Inhibition Of Fusarium Oxysporum Using Pepper Extracts, Taylor Aguiar

Masters Theses

The following contains two projects focused on the fungal pathogen, Fusarium oxysporum. The first project was purely computational in the examination of transposable elements (TEs), which are mobile sequences with the ability to multiply and move in their host genome. In F. oxysporum, TEs such as miniature impala elements are associated with the secreted in xylem gene that are related to its virulence over its host. The F. oxysporum species complex can be utilized as a model system for the examination of TE content and TE expression during the infection cycle. To find whether TEs play a role …

Effects Of Floral Phytochemicals On Growth And Evolution Of A Parasite Of Bumble Bees, Evan Palmer-Young

Doctoral Dissertations

Background: Nectar and pollen are rich in phytochemicals, some of which can reduce disease in pollinators, including agriculturally important honey and bumble bees. Floral phytochemicals could influence the ecological and evolutionary relationships between plants, their pollinators, and parasites that cause pollinator disease. Antiparasitic effects of phytochemicals could be exploited to ameliorate pollinator disease and decline, and thereby sustain pollinator-dependent agricultural production. However, prior studies showed variable effects of phytochemicals on infection in live bees, where differences in bee genotype, abiotic conditions, and parasite strain could influence results. Approach: I used cell cultures of the intestinal trypanosome parasite of bumble bees, …

Effects Of The Floral Phytochemical Eugenol On Parasite Evolution And Bumble Bee Infection And Preference, Evan C. Palmer-Young, Austin C. Calhoun, Anastasiya Mirzayeva, Benn M. Sadd

Organismic and Evolutionary Biology Graduate Student Publication Series

Ecological and evolutionary pressures on hosts and parasites jointly determine infection success. In pollinators, parasite exposure to floral phytochemicals may influence between-host transmission and within-host replication. In the bumble bee parasite Crithidia bombi, strains vary in phytochemical resistance, and resistance increases under in vitro selection, implying that resistance/infectivity trade-offs could maintain intraspecific variation in resistance. We assessed costs and benefits of in vitro selection for resistance to the floral phytochemical eugenol on C. bombi infection in Bombus impatiens fed eugenol-rich and eugenol-free diets. We also assessed infection-induced changes in host preferences for eugenol. In vitro, eugenol-exposed cells initially …

The Role Of Standing Variation In The Evolution Of Weedines Traits In South Asian Weedy Rice (Oryza Spp.), Zhongyung Huang, Shannon Kelly, Rika Matsuo, Lin-Feng Li, Yaling Li, Kenneth M. Olsen, Yulin Jia, Ana L. Caicedo

Biology Department Faculty Publication Series

Weedy rice (Oryza spp.) is a problematic weed of cultivated rice (O. sativa) around the world. Recent studies have established multiple independent evolutionary origins of weedy rice, raising questions about the traits and genes that are essential for the evolution of this weed. Among world regions, South Asia stands out due to the heterogeneity of its weedy rice populations, which can be traced to at least three origins: two through de-domestication from distinct cultivated rice varieties, and one from local wild rice (O. rufipogon/O. nivara). Here we examine five traits considered typical of …

Characterization Of Calcium Homeostasis Parameters In Trpv3 And Cav3.2 Double Null Mice, Aujan Mehregan

Masters Theses

In mammals, calcium influx is required for oocyte maturation and egg activation, as it supports the persistent calcium oscillations induced by fertilization. These oscillations are required for the initiation of embryo development. The molecular identities of the plasma membrane calcium-permeant channels that underlie calcium influx are not established. Among these channels, Transient Receptor Potential Vanilloid, member 3 (TRPV3) allows divalent cations, namely strontium (Sr²⁺) and calcium (Ca²⁺) with high permeability, into cells, and its expression pattern seems to predict an essential role in the initiation of development. Another channel that was identified to be expressed in …

Uncovering Tasselsheath3. A Genomic And Phenotypic Analysis Of A Maize Floral Mutant., Thompson Zhang

Masters Theses

In the modern era, maize has become the most successful crop grown in the United States. According to the USDA over 90 million acres of land are planted to corn and 96.2% of the U.S feed grain production is made up of the cereal. Part of the success of maize is due to its floral architecture, and its pollination technique in which the flower opens, exposing stamens containing pollen into the air. A unique organ called the lodicule functions as a release mechanism, forcing the flower to open. Lodicules from grasses and eudicot petals are homologous, yet there is little …

The Effect Of Pericyte Cell Therapy On Postischemic Neovascularization In Wild Type And Type 2 Diabetic Mice, Katherine E. Hayes

Doctoral Dissertations

Peripheral artery disease is an atherosclerotic disease that causes limb ischemia and has few effective treatments. Stem cell therapy is a promising treatment option, but concomitant diabetes may limit its effectiveness. The purpose of this study was to evaluate the therapeutic potential of skeletal muscle pericytes to augment postischemic neovascularization following the induction of limb ischemia in wild type and type 2 diabetic (T2DM) mice. The hypothesis was that diabetes impairs the ability of skeletal muscle pericytes to augment postischemic neovascularization and differentiate in vivo. Pericytes were isolated via fluorescence activated cell sorting for CD45^-CD34^-CD146 …

The Effects Of Anthropogenic Stress On Nitrogen-Cycling Microbial Communities In Temperate And Tropical Soils, George S. Hamaoui Jr.

Doctoral Dissertations

In this dissertation several research studies are discussed that characterize the effects of anthropogenic, or human-induced, stress on both ammonia-oxidizing and total bacterial soil microbial communities. The disturbances of land-use change in tropical, South American rainforests and artificial warming and nitrogen (N) fertilization in temperate, North American forests were investigated as these disturbances represent past and current disturbances caused by human landscape alteration and climate change. Initially, the response of soil ammonia-oxidizing microbial communities to land-use change from primary rainforest to pasture and, finally, back to secondary forest was determined. Next, these analyses of land-use change effects were expanded to …

Potential Enhancement Of Dietary Isothiocyanates Combination On Biological Activities, Kanyasiri Rakariyatham

Doctoral Dissertations

Isothiocyanates (ITCs) such as allyl isothiocyanate (AIT) and sulforaphane (SFN) are well-known bioactives with wide range of beneficial properties, which may be consumed simultaneously through diets containing cruciferous vegetables. However, biological activities of ITCs in combinations had not been well defined. The present study evaluated the potential efficacy of AIT, SFN and their combinations on three important biological properties: anticancer, anti-inflammation and antioxidant. Our results showed that the combination between AIT and SFN led to a stronger growth inhibition on A549 non-small cell lung cancer cells than treatments with the individual compounds. The enhanced effect was proved to be synergistic …

The Role Of Phenotypic Integration In Mammalian Tooth Function And Jaw Morphological Diversity, Andrew Conith

Doctoral Dissertations

Here I investigate how two major components of the mammalian feeding system, teeth and jaws, are influenced by functional, environment, and developmental factors. First, I build physical models of the molars from two early mammals, Morganucodon and Kuehneotherium, and compare their ability to process a proxy food item. Early mammals were under strong selection to reduce metabolic costs, so any savings in energy during feeding would be advantageous. I tested the ability of both mammals to process a hard and soft food item with material properties similar to that of the insects they would have likely consumed. Morganucodon was …