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Articles 361 - 390 of 1126
Full-Text Articles in Biology
Overcoming Genetic Heterogeneity In Glioblastoma By Targeting Transcriptional Dependencies, Tatenda Mahlokozera
Overcoming Genetic Heterogeneity In Glioblastoma By Targeting Transcriptional Dependencies, Tatenda Mahlokozera
Arts & Sciences Graduate Student Theses and Dissertations
Glioblastoma (GBM) is the most common intrinsic central nervous system malignancy in adults, accounting for approximately 45% of such cancers. Despite advances in chemo- and radiotherapeutic approaches for various malignancies over the past decade, GBM remains an incurable disease with a dismal prognosis. Even after treatment with the current standard of care, which consists of maximal safe surgical resection, radiotherapy, and both concomitant and adjuvant chemotherapy with temozolomide, median survival is only approximately 17 months. Both treatment failure and difficulties in developing novel targeted therapies for GBM have partly been attributed to the molecular and cellular inter- and intra-tumoral heterogeneity …
Understanding The Role Of Involucrin In Skin Inflammation, Alina Schmidt
Understanding The Role Of Involucrin In Skin Inflammation, Alina Schmidt
Arts & Sciences Graduate Student Theses and Dissertations
Terminally differentiated keratinocytes are essential for skin barrier function and are surrounded by an involucrin (IVL)-rich cornified envelope. Increased IVL expression in the epidermis is associated with recent positive selection in European populations, yet the functional significance of this finding is unclear. An upstream enhancer of IVL, the 923 enhancer, regulates IVL expression, and the impact of IVL enhancer variants on involucrin expression in modifying the penetrance of filaggrin (FLG) loss-of-function variants associated with atopic dermatitis (AD) has not been explored. I hypothesize involucrin to modulate the environmentally sensitive Vitamin D receptor (Vdr) activity in the epidermis and involucrin enhancer …
Combining Computer Simulations And Deep Learning To Understand And Predict Protein Structural Dynamics, Michael D. Ward
Combining Computer Simulations And Deep Learning To Understand And Predict Protein Structural Dynamics, Michael D. Ward
Arts & Sciences Graduate Student Theses and Dissertations
Molecular dynamics simulations provide a means to characterize the ensemble of structures that a protein adopts in solution. These structural ensembles provide crucial information about how proteins function, and these ensembles also reveal potential drug binding sites that are not observable from static protein structures (i.e. cryptic pockets). However, analyzing these high- dimensional datasets to understand protein function remains challenging. Additionally, finding cryptic pockets using simulation data is slow and expensive, which makes the appeal of computationally screening for cryptic pockets limited to a narrow set of circumstances. In this thesis, I develop deep learning based methods to overcome these …
Functional And Anatomical Characterization Of Descending Periaqueductal Gray (Pag) Projections And Their Role In Pain Modulation, Jose Gabriel Grajales
Functional And Anatomical Characterization Of Descending Periaqueductal Gray (Pag) Projections And Their Role In Pain Modulation, Jose Gabriel Grajales
Arts & Sciences Graduate Student Theses and Dissertations
Endogenous analgesic pathways embody a potential target for the development for chronic pain therapies. Previous studies have demonstrated the role of the ventrolateral periaqueductal gray (vlPAG) in descending pain modulation. It has been proposed that tonic GABAergic neurotransmission at the level of the vlPAG serves to inhibit efferent excitatory projections that mediate descending analgesia. Disinhibition of these projection neurons allows subsequent activation of rostral ventromedial medulla (RVM) neurons that inhibit nociception at the level of the spinal cord. However, lack of cell-type specificity in these studies has prevented the determination of the role of specific subsets of vlPAG neurons in …
Candida Species And Bacterial Strains In The Vaginal Microbiome, Brett Tortelli
Candida Species And Bacterial Strains In The Vaginal Microbiome, Brett Tortelli
Arts & Sciences Graduate Student Theses and Dissertations
The vaginal environment is a dynamic ecosystem, hosting various microbial species from diverse taxa including bacteria, fungi and viruses. The composition of bacteria within the vaginal microbiome has gained a lot of recent attention and has been associated with reproductive health and disease. The vaginal microbiome of healthy reproductive-aged women is frequently dominated by Lactobacillus species and has low species diversity when compared to other anatomic sites. The composition of the bacterial community is often described in terms of five common community types. Four of the five community types are dominated by a single Lactobacillus species (L. crispatus, L. iners, …
Macrophage Proliferation Machinery Drives Immunosuppression And Pdac Progression (巨噬细胞增值机制抑制肿瘤免疫促进胰腺癌发展), Chong Zuo
Arts & Sciences Graduate Student Theses and Dissertations
Tumor-associated macrophages (TAMs) are abundant in near all solid tumors and are involved in many aspects of cancer progression. The presence of TAMs is negative prognostic indicator in several cancer types including pancreatic cancer. Attempts to target this population by limiting their number in PDAC tumors have not achieved promising results, as compensatory resistance pathways have already been defined. The heterogeneity of TAMs puts another barrier into this targeting strategy, given macrophage subsets are important in maintaining tissue homeostasis and some in performing anti-tumor functions. Previous studies have shown that TAMs in PDAC tumors have dual origins – HSC-derived and …
Molecular Characterization Of Integrase-Rna Interactions And Their Role In The Replication Of Hiv-1 And Other Retroviruses, Christian Shema Mugisha
Molecular Characterization Of Integrase-Rna Interactions And Their Role In The Replication Of Hiv-1 And Other Retroviruses, Christian Shema Mugisha
Arts & Sciences Graduate Student Theses and Dissertations
HIV-1 integrase (IN) enzyme has an emerging non-catalytic role in particle maturation, whichinvolves its binding to the viral genome in virions. Allosteric integrase inhibitors (ALLINIs) and class II integrase substitutions inhibit the binding of IN to the viral genome and cause formation of eccentric non-infectious HIV-1 particles. These viruses are characterized by the mislocalization of the viral ribonucleoprotein complexes between the translucent conical CA lattice and the viral lipid envelope. We have previously demonstrated that IN binding to the viral genome is mediated by basic residues within the C-terminal domain of IN. In the first chapter, we show how basic …
Characterizing The Role Of Interferons In Host-Microbe Interactions In Disseminated Murine Norovirus Infection And Steady-State Hematopoiesis, Forrest Walker
Characterizing The Role Of Interferons In Host-Microbe Interactions In Disseminated Murine Norovirus Infection And Steady-State Hematopoiesis, Forrest Walker
Arts & Sciences Graduate Student Theses and Dissertations
Interferons are critical cytokines responsible for regulating host-microbe interactions in the context of infectious disease as well as homeostatic interactions with the host’s native microbiota. Although significant knowledge regarding the role of interferons in these interactions has been gained in the past sixty years, the diversity of microbes with which the host interacts and the plethora of interferons (with over twenty distinct cytokines organized into three types, based on their receptor utilization) which the host uses in these responses leads to a significant number of interactions which remain to be characterized. Here, we further dissect the role of interferons in …
Antigen Presentation In Central Nervous System Antitumor Immunity, Jay Aaron Bowman-Kirigin
Antigen Presentation In Central Nervous System Antitumor Immunity, Jay Aaron Bowman-Kirigin
Arts & Sciences Graduate Student Theses and Dissertations
Glioblastoma multiforme (GBM) patients face limited treatment options and poor outcomes. The median survival is less than two years, and there are no FDA approved immune therapies. Although GBM itself is an immune-suppressive, heterogeneous tumor, the lack of FDA approved immune therapies might be in part because the cancer immunity cycle is less well understood for GBM than for other tumor types. My studies focused on developing mouse models of malignant glioma that more faithfully recapitulate human GBM from an immunologic perspective, and on defining the role of the conventional dendritic cell 1 subset (cDC1) and lymphatic drainage in central …
Regulation And Function Of Integrin Β3 In Bone-Metastatic Breast Cancer Cells In The Therapeutic Setting, Gregory Chandler Fox
Regulation And Function Of Integrin Β3 In Bone-Metastatic Breast Cancer Cells In The Therapeutic Setting, Gregory Chandler Fox
Arts & Sciences Graduate Student Theses and Dissertations
Breast cancer is the most common non-cutaneous malignancy in women, with over 250,000 patients diagnosed each year in the United States alone. The bone is the most common site of recurrence in breast cancer, affecting over two-thirds of patients with metastatic disease and presenting as the only evidence of distant spread in up to 30%. Clinically, breast cancer bone metastases manifest most often as profoundly osteolytic lesions that negatively impact survival and patient quality of life. Bone-targeted therapies such as bisphosphonates and the anti-RANKL monoclonal antibody denosumab have revolutionized the treatment of bone metastases through inhibition of osteoclast-mediated bone destruction; …
Dnmt3a Regulates Hematopoietic Stem Cells Via Dna Methylation-Independent Functions, Won Kyun Koh
Dnmt3a Regulates Hematopoietic Stem Cells Via Dna Methylation-Independent Functions, Won Kyun Koh
Arts & Sciences Graduate Student Theses and Dissertations
Hematopoiesis is strictly regulated to sustain blood production throughout adult life. De novo DNA methyltransferase 3-alpha (DNMT3A) is one of the major epigenetic regulators found to have an essential role in hematopoietic stem cell (HSC) differentiation. DNMT3A mutations are prevalent in myeloid diseases and malignancies that include acute myeloid leukemia (AML; ~22%), myelodysplastic syndrome (MDS; ~10%), and myeloproliferative neoplasm (MPN; ~8%). Importantly, DNMT3A mutations are not only the founding events of HSC malignant transformation, but they are also occurring as pre-leukemic lesions. Therefore, it is necessary to evaluate the molecular changes that occur in DNMT3A mutant HSCs, and how those …
Unraveling Population Heterogeneity Using Single-Cell Analysis, Wenjun Kong
Unraveling Population Heterogeneity Using Single-Cell Analysis, Wenjun Kong
Arts & Sciences Graduate Student Theses and Dissertations
The human body contains approximately 100 trillion cells, encompassing distinct cell types that serve diverse functions. Understanding cell population heterogeneity is vital for uncovering different biological functions and mechanisms. In addition, cells at transition during continual processes, such as development, reprogramming, and disease, are essential for painting the entire blueprint and highlighting critical stages of the progression trajectory. For instance, cell fate engineering holds much promise for generating clinically valuable cell types from mature somatic cells. Nonetheless, current reprogramming protocols are inefficient, and charting the changes in cell identity during such processes can help design strategies to mitigate the off-target …
Techniques For Spatial Analysis Of C. Elegans Anatomy And Reporter Expression, Nicolette Marie Laird
Techniques For Spatial Analysis Of C. Elegans Anatomy And Reporter Expression, Nicolette Marie Laird
Arts & Sciences Graduate Student Theses and Dissertations
Quantitative analysis of microscopy images is integral to investigating biological phenomena. Despite a variety of tools to aid in analyzing C. elegans images, quantitative microscopy studies are still difficult due to the flexible and deformable nature of the nematode. These differences in posture and shape must first be corrected before analysis. Manual approaches to solve these problems are time intensive and infeasible for large datasets. Additionally, current automated tools rely on high-magnification imaging using labeled nuclei as fixed markers for comparison. Labelling can be achieved either with transgenic animals or fluorescent dyes; however, both of these can be impractical for …
The Role Of Soxe Transcription Factors In Melanoma Initiation, Eva Tulchinsky Kramer
The Role Of Soxe Transcription Factors In Melanoma Initiation, Eva Tulchinsky Kramer
Arts & Sciences Graduate Student Theses and Dissertations
Cutaneous melanoma, a cancer of transformed melanocytes, has the highest mortality rate among skin cancers and remains difficult to treat once metastasized. Melanoma is characterized by high genetic heterogeneity, implicating epigenetic dysfunction as an additional regulator of oncogenesis. Indeed, an increasing number of epigenetic modifiers and modifications have been identified in melanoma linked to faster melanoma onset, and then targeted with therapeutics with success. Thus, identifying and mechanistically characterizing these epigenetic and transcriptional alterations in melanoma will further our understanding of their contributions to oncogenesis and enable more diverse therapeutic options. To evaluate global epigenetic and transcriptional differences between melanocytes …
T Cell Regulation Of Regenerative Environment In Acellular Nerve Allograft Repaired Peripheral Nerves, Deng Pan
Arts & Sciences Graduate Student Theses and Dissertations
Peripheral nerve injury (PNI) is common and has debilitating long term sequelae. Development of new therapies to improve regeneration following PNI is therefore critical. Acellular nerve allografts (ANAs) are increasingly utilized in the clinic for the repair of PNI and an improved mechanistic understanding of nerve regeneration through ANA is important for developing better therapies. Inflammation is an important aspect of regeneration, and the role of macrophage has been increasingly documented. Other aspect of inflammation has not been well-defined. In particular, there is limited understanding on the role of T cells in the regeneration of peripheral nerve. However, evidence in …
Defining The Role Of Rare Genetic Variants That Drive Risk And Pathogenesis Of Alzheimer’S Disease, Matthew James Rosene
Defining The Role Of Rare Genetic Variants That Drive Risk And Pathogenesis Of Alzheimer’S Disease, Matthew James Rosene
Arts & Sciences Graduate Student Theses and Dissertations
Alzheimer’s disease (AD) is the leading cause of dementia and is pathologically defined by the aggregation of extracellular amyloid plaques and intracellular neurofibrillary tangles. Rare heritable mutations within the genes for amyloid precursor protein (APP) and presenilin 1 (PSEN1), and presenilin 2 (PSEN2) cause early onset AD and account for approximately 1% of AD cases. While the majority of AD cases are late-onset (LOAD), which is defined by a markedly more complex genetic architecture that is comprised of many genetic risk factors that influence AD through multiple cellular pathways. The advent of deep sequencing analyses have allowed for the identification …
Vcp: A Gatekeeper For Intracellular Proteopathic Seeding, Jiang Zhu
Vcp: A Gatekeeper For Intracellular Proteopathic Seeding, Jiang Zhu
Arts & Sciences Graduate Student Theses and Dissertations
Protein inclusions such as β-amyloid, tau, α-synuclein, and TDP-43 are considered the pathologic hallmarks of many neurodegenerative diseases. These proteins are prone to misfold, aggregate, and template new aggregates. Accumulating evidence suggests that those proteins in their high-molecular-weight forms can serve as a "seed", spread through an interconnected brain network, and induce new inclusions. Therefore, it is essential to understand the mechanism of proteopathic seeding. In this dissertation, we performed a whole genomic CRISPR-Cas9 KO screening to identify gene modifiers of αS seeding. Within the screening, we found several hits of endolysosomal function and trafficking, including VCP. VCP is a …
The Role Of Fibroblast Growth Factor-9 In Influenza A Virus Pathogenesis, Bradley Edward Hiller
The Role Of Fibroblast Growth Factor-9 In Influenza A Virus Pathogenesis, Bradley Edward Hiller
Arts & Sciences Graduate Student Theses and Dissertations
Influenza A virus (IAV) is a respiratory virus in the Orthomyxoviridae family which causes both seasonal epidemics and pandemics. IAV preferentially infects epithelial cells in the upper and lower respiratory tract, resulting in a range of disease severity from mild upper respiratory infections to potentially-lethal pneumonia. Ultimately, the severity of symptoms and complications from IAV infection depends on control of virus replication in the lungs, the inflammatory nature of the immune response, and the effectiveness of post-infection lung repair to regain pulmonary function. An arsenal of secreted proteins in the lung regulates these antiviral, inflammatory, and regenerative activities during infection, …
Control Of Intestinal Turnover And Cell Death Through Canonical Autophagy Pathways Within Mouse And Human Epithelia, John Steven Ekman
Control Of Intestinal Turnover And Cell Death Through Canonical Autophagy Pathways Within Mouse And Human Epithelia, John Steven Ekman
Arts & Sciences Graduate Student Theses and Dissertations
Regulation of epithelial turnover is essential for the maintenance of the structure and function of the intestine. The balance of intestinal epithelial turnover is known to be modulated by cell-extrinsic cytokines such as Tumor Necrosis Factor (TNF). Likewise, cell-intrinsic modulation of survival and death is afforded by a highly-conserved, multi-step pathway termed autophagy. In this body of work, I have characterized a specific and potent role for autophagy in protecting mouse intestinal epithelial cells (enterocytes) from TNF-triggered cell death. Specifically, I have found that the autophagy initiation factor Atg14 is central to mediating this protective role. Utilizing conditional loss of …
Understanding The Influence Of Individual-Level Sources Of Pathology Variation On Neuroimaging Measures Of Alzheimer Disease, Austin Andrew Mccullough
Understanding The Influence Of Individual-Level Sources Of Pathology Variation On Neuroimaging Measures Of Alzheimer Disease, Austin Andrew Mccullough
Arts & Sciences Graduate Student Theses and Dissertations
The overall goal of this dissertation is to gain a better understanding of how current Alzheimer disease pathologic progression models interact with sources of individual-level variation in pathology to influence overall disease progression in a clinically meaningful way. Many sources of variation, both internal (e.g., genetic mutations, heterogeneity of tau pathology) and external (e.g., diet and exercise, sleep quality), are known to influence disease progression and symptom onset in AD. With the advent of therapies that have shown successful reduction of amyloid load in trials and the rapid progression of anti-tau therapies, we hypothesize that a better understanding of how …
Disuse-Driven Plasticity In The Human Brain, Dillan James Newbold
Disuse-Driven Plasticity In The Human Brain, Dillan James Newbold
Arts & Sciences Graduate Student Theses and Dissertations
Brain circuits are shaped and maintained by active use. We blocked use of motor circuits in three adult participants by constraining the dominant upper extremity in a cast for two weeks, causing loss of strength and fine motor function. Daily resting-state functional magnetic resonance imaging (rs-fMRI) collected for 42-64 days before, during and after casting revealed two sets of changes in brain function. First, large, spontaneous pulses of activity occurred in the disused motor circuits. Pulses showed a consistent pattern of propagation through the disused circuits— occurring earliest in the dorsal anterior cingulate cortex (dACC) and supplementary motor area (SMA), …
Determinants Of Dna Damage Responses During B Cell Development, Rachel Leigh Johnston
Determinants Of Dna Damage Responses During B Cell Development, Rachel Leigh Johnston
Arts & Sciences Graduate Student Theses and Dissertations
Cellular DNA is regularly threatened by both physiologic (normal cellular mechanisms) and genotoxic (external exposures, such as irradiation and chemotherapy) insults. DNA double- stranded breaks (DSBs) are the greatest risk to the genome as they present opportunities for errant repair as mutations or translocations. To minimize these risks, DSBs activate highly conserved signaling pathways to coordinate cell cycle arrest, cell death and DNA repair. During normal development, B cells intentionally create site-specific chromosomal DSBs to assemble the immunoglobulin receptor (Ig) genes necessary for specific responses to pathogens. These programmed DNA breaks are generated by the recombinase activating gene (RAG) complex, …
The Maintenance Of Cd4 And Cd8 T Cell Response To Persistent Antigens, Yu Xia
The Maintenance Of Cd4 And Cd8 T Cell Response To Persistent Antigens, Yu Xia
Arts & Sciences Graduate Student Theses and Dissertations
In response to transient antigen presence in the context of acute infections or vaccinations, antigen-specific naïve T cells clonally expand and differentiate. Most of the expanded cells undergo terminally differentiation and die following antigen clearance to re-establish immune homeostasis. In contrast, when the pathogen persists, such as in the context of chronic viral infections or anti-tumor immunity, while T cells undergo alternative differentiation known as exhaustion due to their reduced functionality, T cells still contribute to pathogen control and its response is sustained for longer duration due to unknown mechanisms. The goal of my thesis work is to understand how …
Multi-Omics Investigation Of Tumor Heterogeneity, Oncogenic Signaling, And Treatment Response In Human Cancers, Yige Wu
Arts & Sciences Graduate Student Theses and Dissertations
Cancer is a highly complex disease with aberrations at the genetic, epigenetic, transcriptomic, and protein levels that drove its phenotypic diversity. Clear cell renal cell carcinoma (ccRCC) is the most common form of kidney cancer, comprising roughly 80% of cases. To define the epigenetic and transcriptomic regulation of ccRCC at the single nucleus (sn) level, we performed snRNA-seq and snATAC-seq in 34 and 28 samples respectively, including primary tumors and normal adjacent tissues, and matched them with bulk proteogenomics data. We identified tumor-specific markers and tumor subpopulations using snRNA-seq, which demonstrated diverse pathway activity within and across patients. PBRM1 and …
Characterization Of Large-Scale Functional Network Organization In The Human Hippocampus, Annie Zheng
Characterization Of Large-Scale Functional Network Organization In The Human Hippocampus, Annie Zheng
Arts & Sciences Graduate Student Theses and Dissertations
The hippocampus is critically important for a diverse range of neural processes, such as episodic memory, prospective memory, affective processing, and spatial navigation. Using both individual-specific precision functional mapping and large-sample group-averaged approaches of characterizing large-scale functional network organization in the human hippocampus, we uncovered general principles of and behaviorally-associated individual differences in hippocampal organization across development in children and adults. We found the hippocampus to be modularly organized along the anterior-posterior axis with the anterior hippocampus being preferentially connected to the default mode network (DMN), as expected. However, the posterior hippocampus was strongly connected to the parietal memory network …
Characterizing Human Gut Bacterial Tir Domains In Vitro, In Gnotobiotic Mice And Malnourished Children, James Stephen Weagley
Characterizing Human Gut Bacterial Tir Domains In Vitro, In Gnotobiotic Mice And Malnourished Children, James Stephen Weagley
Arts & Sciences Graduate Student Theses and Dissertations
Worldwide, malnutrition (undernutrition) is the leading cause of death in children under 5. Studies of healthy members of birth cohorts from low- and middle-income countries have identified a program of gut microbial community development that is disrupted in children with severe acute malnutrition (SAM) and moderate acute malnutrition (MAM). This perturbed gut microbiome development has been linked to the pathogenesis of malnutrition. Repair of this gut microbial dysbiosis in children with MAM with microbiota-directed complementary foods (MDCFs) designed to increase the fitness and expressed beneficial functions of underrepresented bacterial community members restores healthy growth, including improvements in mediators of metabolic …
The Role Of Endoplasmic Reticulum Modifications In Protein Export In Plasmodium Falciparum, Alexander Polino
The Role Of Endoplasmic Reticulum Modifications In Protein Export In Plasmodium Falciparum, Alexander Polino
Arts & Sciences Graduate Student Theses and Dissertations
Following invasion of a host red blood cell (RBC), the malaria parasite Plasmodium falciparum undertakes a program of dramatic host cell renovation. The parasite exports hundreds of effectors into the RBC, altering its shape and rigidity, increasing its permeability to nutrients, and constituting an intracellular transport network that traffics adhesins to the RBC surface. These adhesins mediate binding of the parasitized RBC to the host vascular endothelium, allowing the parasite to avoid destruction in the spleen, but contributing to the pathogenesis of cerebral malaria. Most of these exported effectors bear a pentameric amino acid sequence that marks them for protein …
Massively Parallel Assessment Of The Functional Effects Of De Novo Autism Spectrum Disorder Patient-Derived Genetic Variants In 3’ Untranslated Regions, Tomas Lagunas Jr
Massively Parallel Assessment Of The Functional Effects Of De Novo Autism Spectrum Disorder Patient-Derived Genetic Variants In 3’ Untranslated Regions, Tomas Lagunas Jr
Arts & Sciences Graduate Student Theses and Dissertations
Human genetic studies have identified a large number of patient-derived de novo variants in presumptive regulatory regions of the genome that pose a challenge for interpretation of their effects since the impact of regulatory variants is highly dependent on the cellular context. In particular, current investigations have made significant investments in sequencing the genomes of autism spectrum disorder (ASD) families as a diagnostic method and to further understand the genetic architecture of this complex neurodevelopmental disease. These studies have revealed an enrichment of mutations in the untranslated regions (UTRs) of genes, which are noncoding regulatory regions, in ASD genomes. Assessment …
Cell-Type Specific Expression Of Apolipoprotein E By Astrocytes And Microglia: Implications For The Development Of Amyloid-Β Pathology In Alzheimer Disease, Thomas Mahan
Arts & Sciences Graduate Student Theses and Dissertations
Alzheimer disease (AD) is characterized by two main pathological hallmarks, extracellular amyloid plaques primarily comprised of the amyloid-β (Aβ) peptide, and intracellular neurofibrillary tangles mainly comprised of the tau protein. Although the pathologies underlying AD were first described over one hundred years ago, researchers today are still trying to understand how the development of Aβ pathology is regulated in the hopes of developing more effective treatments. Advances in genetics over the last several decades have allowed for several genetic risk factors to be identified that increase or decrease ones likelihood for developing (AD). Of these genetic risk factors, the strongest …
Quantitative Characterization Of Microbial Ecologies In Dysbiosis And Infection, Eric Keen
Quantitative Characterization Of Microbial Ecologies In Dysbiosis And Infection, Eric Keen
Arts & Sciences Graduate Student Theses and Dissertations
In 1973, Theodosius Dobzhansky famously wrote that nothing in biology makes sense except in the light of evolution. Today, nearly 50 years later, little in microbiology – or in biology, for that matter – makes sense except in the light of genomics. Microbial genomics populates the field with innumerable testable hypotheses for evaluation in vitro and in vivo, allows us to monitor microbial populations in real time and at a massive scale, and underpins our approach to entire domains of microbiology, including microbial evolution. In this Thesis, I present three studies from my graduate research united by their common theme …