Life Sciences Commons^™

Discovery And Characterization Of A Novel Class Of Metabolic Regulators In The Malaria Parasite Plasmodium Falciparum, Ann Marie Guggisberg

Arts & Sciences Electronic Theses and Dissertations

The malaria parasite, Plasmodium falciparum, infects hundreds of millions of people per year and causes hundreds of thousands of deaths. Within the host red blood cell, the parasite relies on glycolysis for energy and synthesis of essential biomolecules. One such anabolic fate of glucose is the synthesis of isoprenoids, a broad and essential class of compounds that participate in a variety of cellular functions. In the face of ever-evolving drug resistance, new inhibitors and better understanding of parasite metabolism are required. The antibiotic fosmidomycin (FSM) targets the methylerythritol phosphate pathway for isoprenoid synthesis and is a well-validated inhibitor of P. …

Genetic Mechanisms For The Maintenance Of Behavioral Mating Barriers In Drosophila, Kathleen M. Mortland

Arts & Sciences Electronic Theses and Dissertations

One of the most successful and diverse systems involved in the maintenance of behavioral barriers between closely related animal species is pheromonal communication. In the fruit fly, contact chemosensation input is especially important during sexual decision-making as it allows for the sensing of sex and species-specific non-volatile cuticular hydrocarbons (CHCs), which function as insect pheromones. However, how pheromonal systems support the maintenance of mating barriers is puzzling since any change in either pheromone ligands or their cognate receptors would carry a fitness cost, which should be eliminated by stabilizing selection. To resolve this evolutionary conundrum I hypothesized that pleiotropic genes …

Epigenomics Of Cell Fate In Development And Disease, Rebecca Faith Lowdon

Arts & Sciences Electronic Theses and Dissertations

Epigenetic features at regulatory elements provide instructive cues for transcriptional regulation during development. However, the particular epigenetic alterations necessary for proper cell fate acquisition and differentiation are not well understood. This dissertation explores the epigenetic dynamics of regulatory elements during development and uses epigenome annotations to document inappropriate transcriptional regulation in disease. First, I summarize my contributions to developing a new algorithm for detecting differential DNA methylation, M&M. I report the application of the M&M algorithm to identify distinct classes of DNA methylation dynamics in surface ectoderm (SE) progenitor cells and SE-derived lineages: epigenome alterations, and differential DNA methylation in …

Kin Selection And Its Discontents, David C. Queller

Biology Faculty Publications & Presentations

Kin selection is a core aspect of social evolution theory, but a small number of critics have recently challenged it. Here I address these criticisms and show that kin selection remains an important explanation for much (though not all) social evolution. I show how many of the criticisms rest on historical idiosyncrasies of the way the field happened to develop, rather than on the real logic and evidence.

The Promise And Pitfalls Of Β-Diversity In Ecology And Conservation, Jonathan A. Myers, Joseph A. Lamanna

Biology Faculty Publications & Presentations

A key challenge in ecology and conservation is to determine how processes at different scales create variation in community composition (β-diversity). In this issue, Oldén & Halme show that grazers increase β-diversity through multiple processes at different scales. We discuss how β-diversity can elucidate fundamental processes of community assembly, challenges in linking processes to patterns, and unresolved questions across scales.

Problems Of Multi-Species Organisms: Endosymbionts To Holobionts, David C. Queller, Joan E. Strassmann

Biology Faculty Publications & Presentations

The organism is one of the fundamental concepts of biology and has been at the center of many discussions about biological individuality, yet what exactly it is can be confusing. The definition that we find generally useful is that an organism is a unit in which all the subunits have evolved to be highly cooperative, with very little conflict. We focus on how often organisms evolve from two or more formerly independent organisms. Two canonical transitions of this type—replicators clustered in cells and endosymbiotic organelles within host cells—demonstrate the reality of this kind of evolutionary transition and suggest conditions that …

Phytochrome B Integrates Light And Temperature Signals In Arabidopsis, Martina Legris, Cornelia Klose, E Sethe Burgie, Cecilia Costigliolo Rojas Rojas, Maximiliano Neme, Andreas Hiltbrunner, Philip A. Wigge, Eberhard Schäfer, Richard D. Vierstra, Jorge J. Casal

Biology Faculty Publications & Presentations

Ambient temperature regulates many aspects of plant growth and development, but its sensors are unknown. Here, we demonstrate that the phytochrome B (phyB) photoreceptor participates in temperature perception through its temperature-dependent reversion from the active Pfr state to the inactive Pr state. Increased rates of thermal reversion upon exposing Arabidopsis seedlings to warm environments reduce both the abundance of the biologically active Pfr-Pfr dimer pool of phyB and the size of the associated nuclear bodies, even in daylight. Mathematical analysis of stem growth for seedlings expressing wild-type phyB or thermally stable variants under various combinations of light and temperature revealed …

Msl1 Is A Mechanosensitive Ion Channel That Dissipates Mitochondrial Membrane Potential And Maintains Redox Homeostasis In Mitochondria During Abiotic Stress, Chun Pong Lee, Grigory Maksaev, Gregory S. Jensen, Monika W. Murcha, Margaret E. Wilson, Mark Fricker, Ruediger Hell, Elizabeth S. Haswell, A Harvey Millar, Lee J. Sweetlove

Biology Faculty Publications & Presentations

Mitochondria must maintain tight control over the electrochemical gradient across their inner membrane to allow ATP synthesis while maintaining a redox-balanced electron transport chain and avoiding excessive reactive oxygen species production. However, there is a scarcity of knowledge about the ion transporters in the inner mitochondrial membrane that contribute to control of membrane potential. We show that loss of MSL1, a member of a family of mechanosensitive ion channels related to the bacterial channel MscS, leads to increased membrane potential of Arabidopsis mitochondria under specific bioenergetic states. We demonstrate that MSL1 localises to the inner mitochondrial membrane. When expressed in …

Purification Of 26s Proteasomes And Their Subcomplexes From Plants, Richard S. Marshall, David C. Gemperline, Richard D. Vierstra

Biology Faculty Publications & Presentations

The 26S proteasome is a highly dynamic, multisubunit, ATP-dependent protease that plays a central role in cellular housekeeping and many aspects of plant growth and development by degrading aberrant polypeptides and key cellular regulators that are first modified by ubiquitin. Although the 26S proteasome was originally enriched from plants over 30 years ago, only recently have significant advances been made in our ability to isolate and study the plant particle. Here, we describe two robust methods for purifying the 26S proteasome and its subcomplexes from Arabidopsis thaliana; one that involves conventional chromatography techniques to isolate the complex from wild-type …

Plastid Osmotic Stress Influences Cell Differentiation At The Plant Shoot Apex, Margaret E. Wilson, Matthew Mixdorf, R Howard Berg, Elizabeth S. Haswell

Biology Faculty Publications & Presentations

The balance between proliferation and differentiation in the plant shoot apical meristem is controlled by regulatory loops involving the phytohormone cytokinin and stem cell identity genes. Concurrently, cellular differentiation in the developing shoot is coordinated with the environmental and developmental status of plastids within those cells. Here, we employ an Arabidopsis thaliana mutant exhibiting constitutive plastid osmotic stress to investigate the molecular and genetic pathways connecting plastid osmotic stress with cell differentiation at the shoot apex. msl2 msl3 mutants exhibit dramatically enlarged and deformed plastids in the shoot apical meristem, and develop a mass of callus tissue at the shoot …

The Role Of Epidermal Enhancer 923 In The Chromatin Architecture And Transcriptional Regulation Of The Epidermal Differentiation Complex, Inez Oh

Arts & Sciences Electronic Theses and Dissertations

The epidermis covers the surface of the skin and provides a functional barrier across the entire body. Epidermal cells or keratinocytes proliferate in the innermost basal layer and migrate upwards into the suprabasal spinous and granular layers as they differentiate, and finally into the terminally differentiated outermost stratum corneum. Keratinocytes undergoing terminal differentiation are marked by tissue-specific concomitant expression of genes encoded in the Epidermal Differentiation Complex (EDC) locus. The EDC genes are organized into four gene families - S100, Sprr, Lce, and Flg-like, which are coordinately expressed upon activation of the terminal differentiation program in keratinocytes. The molecular mechanisms …

Use Of Proteomics To Probe Dynamic Changes In Cyanobacteria, Amelia Yen Nguyen

Arts & Sciences Electronic Theses and Dissertations

Cyanobacteria are unicellular photosynthetic microorganisms that capture and convert light energy to chemical energy, which is the precursor for feed, fuel, and food. These oxygenic phototrophs appear blue-green in color due to the blue bilin pigments in their phycobilisomes and green chlorophyll pigments in their photosystems. They also have diverse morphologies, and thrive in terrestrial, marine water, fresh water, as well as extreme environments. Cyanobacteria have developed a number of protective mechanisms and adaptive responses that allow the photosynthetic process to operate optimally under diverse and extreme conditions. Prolonged deprivation of essential nutrients, such as nitrogen and sulfur, commonly found …

Mechanisms Of Extracellular Vesicle Biogenesis, Charles Eldon Jackson

Arts & Sciences Electronic Theses and Dissertations

Extracellular vesicles (EVs) are important mediators of intercellular communication. Different types of EVs are released from cells by either fusion of late endsomal multivesicular bodies with the plasma membrane (exosomes) or direct budding from the plasma membrane (ectosomes). Topologically equivalent processes including intralumenal vesicle formation for degradation in the endosomal pathway and virus budding from the plasma membrane depend on the ATPase VPS4 and its Endosomal Sorting Complex Required for Transport (ESCRT)-III substrates for membrane fission and release. Whether this machinery is generally required for EV biogenesis has, however, been the subject of debate. Studies of the EV proteome from …

Regulation Of Transcription And Stress Response By Card In Mycobacteria, Ashley Louise Garner

Arts & Sciences Electronic Theses and Dissertations

Mycobacterium tuberculosis, the causative agent of Tuberculosis, infects over one third of the world's population. To control this epidemic, we must develop new chemotherapeutic strategies for treatment, which requires further insight into the physiology of this bacterium. Previous studies have identified CarD as a transcriptional regulator essential during both acute and persistent infection. Depletion of CarD sensitizes strains to a diverse panel of stresses and deregulates several hundred genes and ribosomal RNA (rRNA) which suggested that CarD may be a transcriptional regulator. Chromatin immunoprecipitation sequencing experiments showed that CarD was localized to promoters throughout the genome, suggesting that CarD regulates …

Theory Of Inclusive Fitness, David C. Queller

Biology Faculty Publications & Presentations

A review of Social Evolution and Inclusive Fitness Theory: An Introduction. By James A. R. Marshall. Princeton (New Jersey): Princeton University Press. $39.95. xix + 195 p.; ill.; index. ISBN: 978-0-691-16156-3. 2015.

Autophagic Turnover Of Inactive 26s Proteasomes In Yeast Is Directed By The Ubiquitin Receptor Cue5 And The Hsp42 Chaperone, Richard S. Marshall, Fionn Mcloughlin, Richard D. Vierstra

Biology Faculty Publications & Presentations

Highlights

• The yeast 26S proteasome is degraded by Atg8-mediated autophagy
• Nitrogen starvation and inactivation stimulate proteaphagy via distinct pathways
• Proteasome inhibition is accompanied by extensive ubiquitylation of the complex
• Proteaphagy engages the Cue5 autophagy receptor and the Hsp42 chaperone

Summary

The autophagic clearance of 26S proteasomes (proteaphagy) is an important homeostatic mechanism within the ubiquitin system that modulates proteolytic capacity and eliminates damaged particles. Here, we define two proteaphagy routes in yeast that respond to either nitrogen starvation or particle inactivation. Whereas the core autophagic machineries required for Atg8 lipidation and vesiculation are essential for both routes, the upstream Atg1 …

D-Place: A Global Database Of Cultural, Linguistic And Environmental Diversity, Kathryn R. Kirby, Russell D. Gray, Simon J. Greenhill, Fiona M. Jordan, Stephanie Gomes-Ng, Hans-Jörg Bibiko, Damián E. Blasi, Carlos A. Botero, Claire Bowern, Carol R. Ember, Dan Leehr, Bobbi S. Low, Joe Mccarter, William Divale, Michael C. Gavin

Biology Faculty Publications & Presentations

From the foods we eat and the houses we construct, to our religious practices and political organization, to who we can marry and the types of games we teach our children, the diversity of cultural practices in the world is astounding. Yet, our ability to visualize and understand this diversity is limited by the ways it has been documented and shared: on a culture-by-culture basis, in locally-told stories or difficult-to-access repositories. In this paper we introduce D-PLACE, the Database of Places, Language, Culture, and Environment. This expandable and open-access database (accessible at https://d-place.org) brings together a dispersed corpus of …

A Quantitative Genetic Analysis Of Craniofacial Variation In Baboons, Jessica Lynn Joganic

Arts & Sciences Electronic Theses and Dissertations

This dissertation is an explication of baboon craniofacial variation and its genetic basis. Intraspecific variation is the result of input from and complex interactions among genetic information, functional demands, and developmental processes. The relative effect of each of these on craniofacial variation, as well as the degree of inter-trait covariance, determines whether traits can respond to selection and what that response might look like. Using a sample of pedigreed baboons, I quantify craniofacial variation to address specific questions regarding the distribution and magnitude of phenotypic, genetic, and environmental variation patterns. In addition, I identify regions of the genome containing genetic …

Development And Application Of Comparative Gene Co-Expression Network Methods In Brachypodium Distachyon, Henry David Priest

Arts & Sciences Electronic Theses and Dissertations

Gene discovery and characterization is a long and labor-intensive process. Gene co-expression network analysis is a long-standing powerful approach that can strongly enrich signals within gene expression datasets to predict genes critical for many cellular functions. Leveraging this approach with a large number of transcriptome datasets does not yield a concomitant increase in network granularity. Independently generated datasets that describe gene expression in various tissues, developmental stages, times of day, and environments can carry conflicting co-expression signals. The gene expression responses of the model C3 grass Brachypodium distachyon to abiotic stress is characterized by a co-expression-based analysis, identifying 22 modules …

The Molecular And Cellular Basis For Cold Sensation, Daniel Brenner

Arts & Sciences Electronic Theses and Dissertations

The ability to sense changes in temperature is crucial to surviving harsh environments. Over the last decade several ion channels that have been proposed to be cold sensitive have been identified, most notably TRPM8 and TRPA1. Although these molecules have been extensively studied in vitro, their exact roles in cold sensation in vivo are still debated. This uncertainty is in large part due to problems with the standard methods of testing cold sensitivity in vivo, which often rely on subjective measures of cold responsiveness. Experiments using these subjective measures have been repeated by different groups and have yielded conflicting results, …

Granulocyte-Colony Stimulating Factor Reprograms The Bone Marrow Microenvironment To Suppress B Lymphopoiesis, Ryan Brent Day

Arts & Sciences Electronic Theses and Dissertations

The production of hematopoietic cells in the bone marrow is tightly and dynamically regulated in response to environmental stimuli. In response to infection, the bone marrow increases granulopoiesis at the expense of lymphopoiesis. The mechanisms mediating this shift are poorly understood. We show that treatment with granulocyte-colony stimulating factor (G-CSF), which is often induced during infection, results in marked decline of B lymphocytes at multiple stages of bone marrow B cell development. Transgenic mouse models show that G-CSF acts in a non-cell intrinsic fashion through cells of the monocyte-macrophage lineage to suppress B lymphopoiesis by downregulating important B trophic factors …

Engineering Cre Recombinase For Genome Engineering, Chi Zhang

Arts & Sciences Electronic Theses and Dissertations

Cre recombinase recombines its DNA target, loxP sites, without help of accessory proteins or DNA repair systems. The simplicity of Cre-lox system has been widely utilized for genome editing, especially in mouse genetics. The goal of this dissertation is to constructCrerecombinase variants that will operate uponrecombination target sites (RTs) present within the genome, instead of perturbing the genome by inserting wildtype RTs for subsequent genome engineering. In general, the desired RTs native to the genome are asymmetric. However, the loxP sequence is pseudo-palindromic, requiring a homotetrameric formation of Cre recombinase. As a first step, I broke the symmetry of Cre …

Discrete But Variable Structure Of Animal Societies Leads To The False Perception Of A Social Continuum, Dustin R. Rubenstein, Carlos A. Botero, Eileen A. Lacey

Biology Faculty Publications & Presentations

Animal societies are typically divided into those in which reproduction within a group is monopolized by a single female versus those in which it is shared among multiple females. It remains controversial, however, whether these two forms of social structure represent distinct evolutionary outcomes or endpoints along a continuum of reproductive options. To address this issue and to determine whether vertebrates and insects exhibit the same patterns of variation in social structure, we examined the demographic and reproductive structures of 293 species of wasps, ants, birds and mammals. Using phylogenetically informed comparative analyses, we found strong evidence indicating that not …

Tree-Mycorrhizal Associations Detected Remotely From Canopy Spectral Properties, Joshua B. Fisher, Sean Sweeney, Edward R. Brzostek, Tom P. Evans, Daniel J. Johnson, Jonathan A. Myers, Norman A. Bourg, Amy T. Wolf, Robert W. Howe, Richard P. Philllips

Biology Faculty Publications & Presentations

A central challenge in global ecology is the identification of key functional processes in ecosystems that scale, but do not require, data for individual species across landscapes. Given that nearly all tree species form symbiotic relationships with one of two types of mycorrhizal fungi – arbuscular mycorrhizal (AM) and ectomycorrhizal (ECM) fungi – and that AM- and ECM-dominated forests often have distinct nutrient economies, the detection and mapping of mycorrhizae over large areas could provide valuable insights about fundamental ecosystem processes such as nutrient cycling, species interactions, and overall forest productivity. We explored remotely sensed tree canopy spectral properties to …

Sex Ratio And Gamete Size Across Eastern North America In Dictyostelium Discoideum, A Social Amoeba With Three Sexes, Tracy Edwards Douglas, Joan E. Strassmann, David C. Queller

Biology Faculty Publications & Presentations

Theory indicates that numbers of mating types should tend towards infinity or remain at two. The social amoeba, Dictyostelium discoideum, however, has three mating types. It is therefore a mystery how this species has broken the threshold of two mating types, but has not increased towards a much higher number. Frequency-dependent selection on rare types in combination with isogamy, a form of reproduction involving gametes similar in size, could explain the evolution of multiple mating types in this system. Other factors, such as drift, may be preventing the evolution of more than three. We first looked for evidence of …

The Coursesource Bioinformatics Learning Framework, Sarah C.R. Elgin, Anne Rosenwald, Mark A. Pauley, Lonnie Welch, Robin Wright, Jessamina Blum

Biology Faculty Publications & Presentations

No abstract provided.

Fine-Scale Spatial Ecology Drives Kin Selection Relatedness Among Cooperating Amoebae, Jeff Smith, Joan E. Strassmann, David C. Queller

Biology Faculty Publications & Presentations

Cooperation among microbes is important for traits as diverse as antibiotic resistance, pathogen virulence, and sporulation. The evolutionary stability of cooperation against “cheater” mutants depends critically on the extent to which microbes interact with genetically similar individuals. The causes of this genetic social structure in natural microbial systems, however, are unknown. Here, we show that social structure among cooperative Dictyostelium amoebae is driven by the population ecology of colonization, growth, and dispersal acting at spatial scales as small as fruiting bodies themselves. Despite the fact that amoebae disperse while grazing, all it takes to create substantial genetic clonality within multicellular …

Kin Discrimination In Dictyostelium Social Amoebae, Joan E. Strassmann

Biology Faculty Publications & Presentations

Presentation delivered at the symposium Evidence of Taxa, Clone, and Kin Discrimination in Protists: Ecological and Evolutionary Implications, VII European Congress of Protistology, University of Seville, 5–10 September 2015, Seville Spain.

Evolved cooperation is stable only when the benefactor is compensated, either directly or through its relatives. Social amoebae cooperate by forming a mobile multicellular body in which, about 20% of participants ultimately die to form a stalk. This benefits the remaining individuals that become hardy spores at the top of the stalk, together making up the fruiting body. In studied species with stalked migration, P. violaceum, D. purpureum, and …

A Parallel G Quadruplex-Binding Protein Regulates The Boundaries Of Dna Elimination Events Of Tetrahymena Thermophila, Christine M. Carle, Hani S. Zaher, Douglas L. Chalker

Biology Faculty Publications & Presentations

Guanine (G)-rich DNA readily forms four-stranded quadruplexes in vitro, but evidence for their participation in genome regulation is limited. We have identified a quadruplex-binding protein, Lia3, that controls the boundaries of germline-limited, internal eliminated sequences (IESs) of Tetrahymena thermophila. Differentiation of this ciliate’s somatic genome requires excision of thousands of IESs, targeted for removal by small-RNA-directed heterochromatin formation. In cells lacking LIA3 (ΔLIA3), the excision of IESs bounded by specific G-rich polypurine tracts was impaired and imprecise, whereas the removal of IESs without such controlling sequences was unaffected. We found that oligonucleotides containing these polypurine tracts formed …

Crystal Structure Of Deinococcus Phytochrome In The Photoactivated State Reveals A Cascade Of Structural Rearrangements During Photoconversion, E Sethe Burgie, Junrui Zhang, Richard D. Vierstra

Biology Faculty Publications & Presentations

Phytochromes are photochromic photoreceptors responsible for a myriad of red/far-red light-dependent processes in plants and microorganisms. Interconversion is initially driven by photoreversible isomerization of bilin, but how this alteration directs the photostate-dependent changes within the protein to actuate signaling is poorly understood. Here, we describe the structure of the Deinococcus phytochrome photosensory module in its near complete far-red light-absorbing Pfr state. In addition to confirming the 180° rotation of the D-pyrrole ring, the dimeric structure clearly identifies downstream rearrangements that trigger large-scale conformational differences between the dark-adapted and photoactivated states. Mutational analyses verified the importance of residues surrounding the bilin …