Alterations Of The Gut Mycobiome In Patients With Ms - A Bioinformatic Approach, Saumya Shah

Honors Scholar Theses

The mycobiome is the fungal component of the gut microbiome and is implicated in several autoimmune diseases. However, its role in multiple sclerosis (MS) has not been studied. We performed descriptive and formal statistical tests using the R language to characterize the gut mycobiome in people with MS (pwMS) and healthy controls. We found that the microbiome composition of multiple sclerosis patients is different from healthy people. The mycobiome had significantly higher alpha diversity and inter-subject variation in pwMS than controls. Additionally, Saccharomyces and Aspergillus were over-represented in pwMS. Different mycobiome profiles, defined as mycotypes, were associated with different bacterial …

Identifying The Cell Composition And Clonal Diversity Of Supratentorial Ependymoma Using Single Cell Rna-Sequencing, James He

University Scholar Projects

Ependymoma is a primary solid tumor of the central nervous system. Supratentorial ependymoma (ST-EPN), a subtype of ependymomas, is driven by an oncogenic fusion between the ZFTA and RELA genes in 70% of cases. We introduced this fusion into neural progenitor cells of mice embryos via in utero electroporation of a non-viral binary piggyBac transposon system containing ZFTA-RELA. From preliminary data in the LoTurco lab, inducing the expression of ZFTA-RELA into different neural progenitor cells produces tumors of varying lethality and cellular composition. To define the cellular composition and subclonal diversity of ST-EPN tumors, we used single cell RNA-sequencing to …

Single-Fluorophore Sensors For Mechanical Force In Living Cells, Sarah Kricheff

Honors Scholar Theses

Mechanotransduction is the process by which a mechanical stimulus is converted to a cellular signal. This process is heavily influential of cell morphology, differentiation, and behavior. However, altered levels of mechanical stimuli are also found in many pathological contexts. For example, cancerous cells have stiffer surrounding tissue than healthy cells, and research suggests that this alters cell behavior and promotes metastasis. Despite these findings, the cellular processes behind these signaling alterations remain widely unknown. Understanding these cascades is critical, as involved proteins can give us a deeper understanding of the role of mechanotransduction, and certain proteins can potentially be targeted …

Identification And Analysis Of Feather Degrading Bacteria: A Search For Keratinase Genes, Nehal Navali

Honors Scholar Theses

Over two million tons of feather waste is generated annually by the poultry industry, the majority of which goes into landfills due to the difficulty of degrading its major component keratin. Although a portion of feather waste is eliminated via incineration or chemical treatment, the use of Feather Degrading Bacteria (FDB) has been proposed as a cheap and eco-friendly alternative. FDBs have been consistently isolated from the feather microbiome of birds and contain genes coding for the specialized protein keratinase which is able to degrade feathers. By doing so, feather waste, which is rich in nutrients, can be repurposed as …

Modeling And Analyzing An Optogenetic System For Photoactivatable Protein Dissociation, Anvin Thomas, James Schaff

Honors Scholar Theses

Computational modeling of cell-cell interactions can grant clues and can answer questions about an experiment, especially for observations about binding interactions and kinetics. This approach was used to investigate an interaction between a light-oxygen-voltage (LOV) domain and an engineered protein called Zdark (Zdk). The LOV domain is membrane-bound while Zdk is cytosolic. The LOV domain and Zdk bind strongly in dark (K_d 26.2 nM), and weakly upon exposure to blue light (K_d > 4 μM). Total internal reflection fluorescence (TIRF) images are acquired of Zdk, the fluorescent species bound to a mCherry tag, and the loss of fluorescence is …

Identification, Characterization, And Life Cycle Of Intein-Associated Homing Endonucleases, Joshua J. Skydel

Honors Scholar Theses

Inteins are molecular parasites that have been identified in unicellular organisms from the three domains of life. The intein self-excises following translation of the host gene, and therefore incurs a fitness cost for its carrier. The symbiotic state of the intein to its host is dependent on the presence or absence of a homing endonuclease domain, which facilitates horizontal transfer of the molecule. Identification of this domain provides information on the evolutionary history of the intein, as well as patterns of horizontal gene transfer in microbial communities. I have therefore developed Hidden Markov Models (HMMs) to identify homing endonuclease domains …

An Exploration Of The Phylogenetic Placement Of Recently Discovered Ultrasmall Archaeal Lineages, Jeffrey M. O'Brien

Honors Scholar Theses

In recent years, several new clades within the domain Achaea have been discovered. This is due in part to microbiological sampling of novel environments, and the increasing ability to detect and sequence uncultivable organisms through metagenomic analysis. These organisms share certain features, such as small cell size and streamlined genomes. Reduction in genome size can present difficulties to phylogenetic reconstruction programs. Since there is less genetic data to work with, these organisms often have missing genes in concatenated multiple sequence alignments. Evolutionary Biologists have not reached a consensus on the placement of these lineages in the archaeal evolutionary tree. There …

Detection Of Genomic Inversion From Single End Read, Pankaj Ghimire

Master's Theses

Structural Variations (SVs) are genomic rearrangements that include both copy-number variants,such as insertion,deletions, duplications and balanced variants like inversion and translocations. These SVs are getting more attentions for research and investigation because of their role on human phenotype, genetic diseases and genomic rearrangements. Evolution of Next-generation Sequencing has provided golden opportunities to investigate these variants and make their wider and clear spectrum in human genome. This investigation includes identification of type of SVs and their breakpoints at base pair level. For their effective identification and breakpoint resolution, many techniques are devised mainly based on paired end read. With relatively low …

Desert Hedgehog Is A Mammal-Specific Gene Expressed During Testicular And Ovarian Development In A Marsupial, William A. O'Hara

Master's Theses

Desert hedgehog (DHH) belongs to the hedgehog gene family that act as secreted intercellular signal transducers. DHH is an essential morphogen for normal testicular development and function in both mice and humans but is not present in the avian lineage. Like other hedgehog proteins, DHH signals through the patched (PTCH) receptors 1 and 2. Here we examine the expression and protein distribution of DHH, PTCH1 and PTCH2 in the developing testes of a marsupial mammal (the tammar wallaby) to determine whether DHH signalling is a conserved factor in gonadal development in all therian mammals.