Amino Acids, Peptides, and Proteins Commons^™

Listeria Adhesion Protein Orchestrates Caveolae-Mediated Apical Junctional Remodeling Of Epithelial Barrier For Listeria Monocytogenes Translocation, Rishi Drolia, Donald B. Bryant, Shivendra Tenguria, Zuri A. Jules-Culver, Jessie Thind, Breanna Amelunke, Donqi Liu, Nicholas L. F. Gallina, Krishna K. Mishra, Manalee Samaddar, Manoj R. Sawale, Dharmendra K. Mishra, Abigail D. Cox, Arun K. Bhunia

Biological Sciences Faculty Publications

The cellular junctional architecture remodeling by Listeria adhesion protein-heat shock protein 60 (LAP-Hsp60) interaction for Listeria monocytogenes (Lm) passage through the epithelial barrier is incompletely understood. Here, using the gerbil model, permissive to internalin (Inl) A/B-mediated pathways like in humans, we demonstrate that Lm crosses the intestinal villi at 48 h post-infection. In contrast, the single isogenic (lap− or ΔinlA) or double (lap−ΔinlA) mutant strains show significant defects. LAP promotes Lm translocation via endocytosis of cell-cell junctional complex in enterocytes that do not display luminal E-cadherin. In comparison, InlA facilitates …

Aggregation-Induced Emission Probe For Alzheimer's Detection And Treatment Screening, Gemini Ramlo

Williams Honors College, Honors Research Projects

The proposed project is to research if ROF-2, an aggregation-induced emitter, can be used to screen medications for Alzheimer's Disease and to accurately detect this disease, along with its progression. This will be done through multiple incubation periods using different identifiers that have already been solidified within Alzheimer's research to prove its ability and accuracy within screening and detection regarding this disease.

Molecular Determinants Of Trp Channel Gating, Briar J. Bell

Theses and Dissertations (ETD)

Transient Receptor Potential (TRP) ion channels are a family of proteins that contribute to a myriad of physiological functions. They have been extensively studied since their discovery 35 years ago; however, there are still many questions regarding the mechanisms by which they function. This family of proteins is characterized by a generally shared structure: an intracellular N terminus featuring ankyrin repeats, six transmembrane helices including the pore domain, a re-entrant loop and TRP helix, and an intracellular C terminus with varying structure. Each of these regions has been implicated in the regular function of TRPs, while mutations that alter trafficking …

Quantum Dots' Toxicity: A Multi-Level Investigation On The Impact Of Quantum Dots On The Actin Cytoskeleton, Nhi Le

Graduate Theses/Dissertations

Quantum dots (QDs) are fluorescence nanomaterials with unique optical and physical properties. As such, they are highly sought after for their potential use in several biomedical and industrial applications. Despite their vast potential, recent studies have suggested that quantum dots are toxic to cells. Yet, the mechanism of quantum dots’ toxicity remains unclear. As such, my thesis aims to comprehensively examine the mechanism of quantum dots’ toxicity, emphasizing how quantum dots disrupt the actin cytoskeleton. In this study, I used RNA sequencing and mass spectrometry to investigate the influence of CdSe/ZnS QDs on the transcriptomic proteomic level of Saccharomyces cerevisiae …

Host-Defense Piscidin Peptides As Antibiotic Adjuvants Against Clostridioides Difficile, Adenrele Oludiran, Areej Malik, Andriana C. Zourou, Yonghan Wu, Steven P. Gross, Albert Siryapon, Asia Poudel, Kwincy Alleyne, Savion Adams, David S. Courson, Myriam L. Cotten, Erin B. Purcell

Chemistry & Biochemistry Faculty Publications

The spore-forming intestinal pathogen Clostridioides difficile causes multidrug resistant infection with a high rate of recurrence after treatment. Piscidins 1 (p1) and 3 (p3), cationic host defense peptides with micromolar cytotoxicity against C. difficile, sensitize C. difficile to clinically relevant antibiotics tested at sublethal concentrations. Both peptides bind to Cu²⁺ using an amino terminal copper and nickel binding motif. Here, we investigate the two peptides in the apo and holo states as antibiotic adjuvants against an epidemic strain of C. difficile. We find that the presence of the peptides leads to lower doses of …

Hybridization Kinetics Of Four-Way Junctions Localized On A Dna Scaffold, Katherine N. Taylor

Honors Undergraduate Theses

DNA computing is an ever-growing field with scientists trying to design structures that optimize logic gate communication to develop fast, biologically compatible, computational structures. We hypothesize that by using the principles of DNA computing, it is possible to design a DNA tile capable of studying localized DNA hybridization that can differentiate between oligonucleotides of different structural conformations. This includes synthetically manipulating DNA into a nanostructure that can perform Boolean logic functions to calculate the different rates of hybridization. To test our hypothesis, we designed a DNA Tile that incorporated a 4WJ using YES logic. Linear and hairpin single-stranded (ss) DNA …

Developing Cellular Systems To Elucidate Rna Structural Dynamics Of Cag Expansion Transcripts In Spinocerebellar Ataxias, Victoria Demeo

Electronic Theses & Dissertations (2024 - present)

Spinocerebellar ataxias (SCAs) are a diverse group of over 40 genetically heterogeneous neurodegenerative disorders, many of which are caused by a trinucleotide CAG repeat expansion in the coding region of specific genes. These expansions lead to the production of polyglutamine (polyQ) tracts that interfere with normal protein function, triggering cellular dysfunction and contributing to disease pathogenesis. The most well-known of these SCAs, such as SCA1, SCA2, and SCA3, exhibit progressive neurodegeneration, yet the precise mechanisms through which these mutations cause disease remain poorly understood.

A significant challenge in studying CAG repeat expansion disorders lies in the complexity of the disease …

Receptor-Targeted Next-Generation Probiotics Ameliorate Mammalian Colitis, Nicholas L. F. Gallina, Vignesh Nathan, Akshay Krishnakumar, Dongqi Liu, Rishi Drolia, Nicole Irrizary Tardi, Yang Fu, Manalee Samadar, Shivendra Tenguria, Alvin Cai, Ruth Eunice Centeno-Martinez, Timothy A. Johnson, Abigail Cox, Lavanya Reddivari, Bruce Applegate, Xingjian Bai, Luping Xu, Deepti Tanjore, Ramesh Vemulapalli, Rahim Rahimi, Arun K. Bhunia

Biological Sciences Faculty Publications

Introduction: a loss of intestinal barrier function, inflammation, and an elevated expression of epithelial heat shock protein 60 (Hsp60) are features of an inflamed bowel. Probiotics have been used to alleviate colitis-induced pathologies, but offer poor adhesion and adaptation to the diseased gut. We hypothesize that enhancing probiotic adhesion in the inflamed bowel may ameliorate such pathologies. Listeria adhesion protein (LAP; 94-kDa acetaldehyde alcohol dehydrogenase) aids Listeria attachment to the epithelial cells by interacting with the mammalian receptor Hsp60. Bioengineered Lactobacillus casei probiotics (BLPs) expressing LAP showed strong interaction with epithelial Hsp60, a high immunomodulatory response, and sustained epithelial barrier …

Revealing The Elusive Mechanism Of Action Of The Lipid Chaperone Fatty Acid Binding Protein 4, Abdul J. Castillo Ibanez

Theses and Dissertations

Fatty acid binding proteins (FABPs) are pivotal in orchestrating lipid trafficking within cells. This dissertation aims to reveal the mechanism of action of adipocyte FABP (FABP4) by meticulously detailing steps for producing uniformly isotopically labeled protein, understanding dynamics and structural changes in aqueous conditions, analyzing protein-membrane interaction with membrane mimicking models, and revealing its membrane-bound state through novel NMR structural elucidation. Chapter 1 provides an overview of FABP4's indispensable role in lipid trafficking, emphasizing its significance in maintaining cellular homeostasis and metabolic regulation. Chapter 2 delves into the optimization of FABP4 protein expression and proposes a high yield recovery and …

Flexible Fitting Of Alphafold2-Predicted Models To Cryo-Em Density Maps Using Elastic Network Models: A Methodological Affirmation, Maytha Alshammari, Jing He, Willy Wriggers

Computer Science Faculty Publications

Motivation: This study investigates the flexible refinement of AlphaFold2 models against corresponding cryo-electron microscopy (cryo-EM) maps using normal modes derived from elastic network models (ENMs) as basis functions for displacement. AlphaFold2 generally predicts highly accurate structures, but 18 of the 137 models of isolated chains exhibit a TM-score below 0.80. We achieved a significant improvement in four of these deviating structures and used them to systematically optimize the parameters of the ENM motion model.

Results: We successfully refined four AlphaFold2 models with notable discrepancies: lipid-preserved respiratory supercomplex (TM-score increased from 0.52 to 0.69), flagellar L-ring protein (TM-score increased from 0.53 …