Molecular Biology Commons^™

Nsp3 Protein-Portion Interaction Of Sars-Cov-2 Using Two Yeast-Hybrid System, Ghadeer Jassem Zakareya

Selected Full-Text Master Theses 2021-

The NSP3 protein of SARS-CoV-2 plays a crucial role in the virus-host interaction during infection. This thesis explores the protein-protein interactions between NSP3 and host factors, shedding light on their significance in viral replication and pathogenesis. NSP3 is known to interact with various host proteins involved in key cellular processes, including innate immune response modulation, RNA processing and protein degradation pathways. Understanding these interactions is essential for developing targeted therapeutic strategies against COVID-19. Application of The Matchmaker GAL4Two-Hybrid Systems, to isolate the NSP3 protein and study the interactions, elucidating the NSP3 host protein interactions and attempting to identify potential key …

Fxr Agonism With Bile Acid Mimetic Reduces Pre-Clinical Triple-Negative Breast Cancer Burden, Sydney Joseph, Samson Eugin Simon, Margaret S. Bohm, Minjeong Kim, Madeline E. Pye, Boston W. Simmons, Dillon G. Graves, Stacey M. Thomas-Gooch, Ubaid A. Tanveer, Jeremiah R. Holt, Suriyan Ponnusamy, Laura M. Sipe, Et Al.

Biological Sciences Research

Bariatric surgery is associated with improved outcomes for several cancers, including breast cancer (BC), although the mechanisms mediating this protection are unknown. We hypothesized that elevated bile acid pools detected after bariatric surgery may be factors that contribute to improved BC outcomes. Patients with greater expression of the bile acid receptor FXR displayed improved survival in specific aggressive BC subtypes. FXR is a nuclear hormone receptor activated by primary bile acids. Therefore, we posited that activating FXR using an established FDA-approved agonist would induce anticancer effects. Using in vivo and in vitro approaches, we determined the anti-tumor potential of bile …

Why Should Early-Career Scientists Publish In Society Journals, Stephen K. Dolan, Lori D. Banks, Wenqi Yu

Molecular Biosciences Faculty Publications

In this editorial, written by early-career scientists, we advocate for the invaluable role of society journals in our scientific community. By choosing to support these journals as authors, peer reviewers, and as editors, we can reinforce our academic growth and benefit from their re-investment back into the scientific ecosystem. Considering the numerous clear merits of this system for future generations of microbiologists and more broadly, society, we argue that early-career researchers should publish our high-quality research in society journals to shape the future of science and scientific publishing landscape.

The Inaugural Mbio Junior Editorial Board—Lessons Learned And The Path Forward Toward Improving The Peer Review Process, Cynthia Ayefoumi Adinortey, Stephen K. Dolan, Sarah Doore, Rebeccah Lijek, Diana Priscila Pires, Wenqi Yu, Elizabeth B. Draganova, Lennart Schada Von Borzyskowski

Molecular Biosciences Faculty Publications

The inaugural Junior Editorial Board (JEB) of mBio consisted of 64 early-career researchers active from 2022 to 2023. The goal of the JEB was to train early-career researchers in the art of peer review under the guidance of experienced editors. JEB members gained hands-on experience in peer review by participating in modules detailing the publishing process through the lenses of the journal, editor, and reviewer. Ultimately, JEB members applied this new knowledge by reviewing mBio manuscripts. Here, we summarize the background, the mission, and the achievements of the first mBio JEB. We also include possible trajectories for the future editions …

Developing Partnerships For Academic Data Science Consulting And Collaboration Units, Marianne Huebner, Laura Bond, Felesia Stukes, Joel Herndon, David J. Edwards, Gina-Maria Pomann

Biomedical Research Institute Publications and Presentations

Data science consulting and collaboration units (DSUs) are core infrastructure for research at universities. Activities span data management, study design, data analysis, data visualization, predictive modelling, preparing reports, manuscript writing and advising on statistical methods and may include an experiential or teaching component. Partnerships are needed for a thriving DSU as an active part of the larger university network. Guidance for identifying, developing and managing successful partnerships for DSUs can be summarized in six rules: (1) align with institutional strategic plans, (2) cultivate partnerships that fit your mission, (3) ensure sustainability and prepare for growth, (4) define clear expectations in …

Revolutionizing Our Understanding Of Specific Platelet-Pathogen Interactions, Hammodah Rawhi Hammodah Alfar

Theses and Dissertations--Molecular and Cellular Biochemistry

Aside from their classical role in maintaining hemostasis, platelets are considered first-line vascular guardians that influence both the innate and adaptive immune systems. This is mediated by either direct interactions with immune cells or through the release of pre-stored cytokines and chemokines upon interacting with pathogens such as viruses. While this establishes platelets as potential players in the response to pathogens, it remains unclear what platelets can do with pathogens and how important that is to immune responses, especially against viruses. Most systemic viremias, such as HIV-1, present with mild thrombocytopenia, which is mediated through several mechanisms such as a …

Calcium And Proteasomal Regulation Of Er-To-Golgi Protein Transport In Neurons, Samuel A. Galindo

Undergraduate Theses, Professional Papers, and Capstone Artifacts

Regulatory mechanisms of protein trafficking from the endoplasmic reticulum (ER) are critical to understand since neurodegenerative diseases involve defects in this process leading to chronic ER stress and cell death. This study aimed to better understand the calcium regulatory mechanisms of ER-to-Golgi trafficking in hybrid neuroglioblastoma cells (NG108). Specifically, we asked whether proteasomal degradation of transport machinery was involved in the previously demonstrated upregulation of ER-to-Golgi transport evoked by calcium signaling. Based upon previous literature, we believe that the calcium induced increase in transport is due to the activation of the calcium sensitive regulatory protein apoptosis linked gene 2 (ALG-2) …

Iron–Sulfur Cluster Assembly Scaffold Protein Iscu Is Required For Activation Of Ferric Uptake Regulator (Fur) In Escherichia Coli, Huangen Ding

Faculty Publications

No abstract provided.

Advancing Biological Applications Through Microfluidic-Based Tool Development, K.M. Taufiqur Rahman

Electronic Theses and Dissertations

This research undertook an interdisciplinary approach, integrating bioengineering, microbiology, molecular biology, and systems biology to investigate bacterial dynamics behavior. Specifically, it delved into the development of microfluidic devices for biological applications such as bacterial cell counts, real-time observation of plant roots (here, specialized lectin-coated microbeads are used that mimic root characteristics), and soil microbe interactions. Furthermore, Next-Generation Sequencing and systems biology methodologies were employed to explore the intricate, multifaceted survival mechanisms of Escherichia coli persister population. Studying and quantifying persisters or testing for the existence of VBNC (viable but nonculturable) is challenging. These experiments require precise counts. It has been …

Rps6kb1 Is A Critical Target For Overcoming Tumor Lineage Plasticity And Therapy Resistance, Saptadwipa Ganguly

Theses and Dissertations--Toxicology and Cancer Biology

Most tumors initially respond to treatment, yet refractory clones subsequently develop owing to resistance mechanisms which can be classified as intrinsic or extrinsic resistance. The intrinsic resistance is usually present prior to any treatment whereas the extrinsic resistance develops as a result of exposure to some kind of therapy. In order to target these “therapy resistant” tumor cells an unbiased screen of an FDA-approved drug library against cancer cells was performed. This was followed by synthesis of chemical analogs of the most effective drug.

The studies led to the identification of a derivative of the antihistamine drug ebastine, designated Super-ebastine …

An Rnai-Based Approach To Ips Calligraphus Management: A Promising Strategy For Forest Protection, Mary Wallace

Theses and Dissertations--Entomology

As climate change leads to more frequent and severe extreme weather, host tree stress is increasing the occurrence of large-scale bark beetle outbreaks. One such beetle, Ips calligraphus (Germar), a native bark beetle in the southeastern United States, has traditionally been considered a secondary pest of pine trees. Management has relied on silvicultural practices that enhance forest resilience, enabling host trees to effectively use natural defenses to deter beetle infestation. However, during periods of forest stress caused by storms, droughts, human disturbance, and other factors, beetle outbreaks can cause considerable ecological and economic damage.

Addressing worsening I. calligraphus outbreaks will …

Contributions Of The Replication Initiator Protein Dnaa To Physiology And Virulence Of The Lyme Disease Spirochete, Andrew Krusenstjerna

Theses and Dissertations--Microbiology, Immunology, and Molecular Genetics

Borrelia burgdorferi, the etiological agent of Lyme disease, is the most prevalent vector-borne disease in the United States. The spirochetal population is naturally maintained by consistently cycling between Ixodid ticks and small vertebrates. To survive within these diverse niches, B. burgdorferi has evolved a unique physiology and regulatory network to sense and respond to environmental fluxes. Replication is a hallmark of the Lyme spirochete’s enzootic life cycle, specifically at the nymphal tick-to-vertebrate interface. The mechanisms and regulatory schema for the basic cellular processes in B. burgdorferi, or indeed any member of the phylum spirochaetota, are largely unknown. The central hypothesis …

Abl1/2 And Ddr1 Cooperate To Stabilize Braf/Craf To Drive Erk1/2 Reactivation And Promote Mek Inhibitor Resistance In Nras-Mutant Melanomas, Anastasia Lyon

Theses and Dissertations--Pharmacology and Nutritional Sciences

This study addresses the escalating incidence of NRAS-mutant melanomas, a type of skin cancer lacking FDA-approved targeted therapies. Despite ongoing research targeting the RAF/MEK/ERK pathway, existing drugs fail to enhance progression-free survival due to acquired resistance. This project identifies a novel role for ABL1/2 and DDR1 kinases in driving drug resistance and proliferation of NRAS-mutant melanoma cells. ABL1/2 and DDR1 cooperate to promote RAF homodimerization and protein stability in order to reactivate MEK/ERK signaling to drive MEK1/2 inhibitor (MEKi) resistance and promote survival of resistant cells. By targeting ABL1/2 and DDR1 with nilotinib, a FDA-approved anti-leukemic inhibitor, we …

Practical Challenges In Delivering Dsrna For Woody Plant Protection, Zachary Bragg

Theses and Dissertations--Entomology

Unprecedented weather events associated with climate change, coupled with extensive anthropogenic stresses, have reduced the effectiveness of traditional forest pest management approaches, which can no longer keep pace with invasive species overwhelming naïve landscapes and native pests experiencing eruptive and expansive outbreaks. Double-stranded RNA-(dsRNA) mediated gene silencing, a type of RNA interference (RNAi), has been coopted for use as a biopesticide against a multitude of agricultural and horticultural pests and could serve as a powerful tool for woody plant protection. While effective initiation of gene silencing and subsequent mortality have been demonstrated in multiple tree pests, effective and efficient methods …

Role Of Autophagy-Related Genes In Lipid Transport For Efficient Replication Of Tombusviruses, Yuanrong Kang

Theses and Dissertations--Plant Pathology

Tombusviruses are positive-strand RNA viruses, which utilize numerous co-opted host factors and massive de-novo synthesized membrane resources to modify host membranes and form large viral replication organelles (VROs). Among plenty of host cellular processes, autophagy emerges as a potential membrane resource for VROs formation due to its ability to de-novo generate the double membrane structures, known as autophagosomes. Besides, as an important host defense pathway, autophagy is also a target for tombusviruses to prevent its antiviral activities. In this study, I identify the role of key autophagy related genes, Atg11, Atg8, and Atg2, which are involved in autophagosome formation, and …

Exploring 3d Genome Interaction And Epigenetic Regulation Via Swi/Snf Complex And Deep Learning Models, Ruoyun Wang

Dartmouth College Ph.D Dissertations

The three-dimensional organization of the genome is fundamental in regulating gene expression and maintaining cellular function. This organization's complexities, influenced by epigenetic marks and chromatin remodeling complexes, are crucial for understanding genomic regulation. Among these, the SWI/SNF complexes are key, facilitating chromatin accessibility and regulating gene activity across cell types. The first part of my dissertation focuses on SWI/SNF complexes, exploring their role in chromatin remodeling and their impact on 3D genome architecture. Utilizing next-generation sequencing (NGS) techniques, this section investigates the interplay between these complexes and chromatin structure. During my research on the SWI/SNF complex, I was intrigued by …

Inflammation And Tumor Progression: The Differential Impact Of Saa In Breast Cancer Models, Daniel Wilhelm Olivier, Carla Eksteen, Manisha Du Plessis, Louis De Jager, Lize Engelbrecht, Nathaniel Wade Mcgregor, Preetha Shridas, Frederick C. De Beer, Willem J. S. De Villiers, Etheresia Pretorius, Anna-Mart Engelbrecht

Saha Cardiovascular Research Center Faculty Publications

Background: Previous research has shown that the Serum Amyloid A (SAA) protein family is intricately involved in inflammatory signaling and various disease pathologies. We have previously demonstrated that SAA is associated with increased colitis disease severity and the promotion of tumorigenesis. However, the specific role of SAA proteins in breast cancer pathology remains unclear. Therefore, we investigated the role of systemic SAA1 and SAA2 (SAA1/2) in a triple-negative breast cancer mouse model.

Methods: Syngeneic breast tumors were established in wild-type mice, and mice lacking the SAA1/2 (SAADKO). Subsequently, tumor volume was monitored, species survival determined, the inflammatory profiles of mice …

Cyp6g2 Is The Major P450 Epoxidase Responsible For Juvenile Hormone Biosynthesis In Drosophila Melanogaster, Qiangqiang Jia, Liu Yang, Jiamin Wen, Suning Liu, Di Wen, Wei Luo, Weihua Wang, Subba R. Palli, Li Sheng

Entomology Faculty Publications

Background Juvenile hormones (JH) play crucial role in regulating development and reproduction in insects. The most common form of JH is JH III, derived from MF through epoxidation by CYP15 enzymes. However, in the higher dipterans, such as the fruitfly, Drosophila melanogaster, a bis-epoxide form of JHB3, accounted most of the JH detected. Moreover, these higher dipterans have lost the CYP15 gene from their genomes. As a result, the identity of the P450 epoxidase in the JH biosynthesis pathway in higher dipterans remains unknown.

Results In this study, we show that Cyp6g2 serves as the major JH epoxidase responsible for …

N(Alpha)-Acetyltransferase 40-Mediated Histone Acetylation Plays An Important Role In Ecdysone Regulation Of Metamorphosis In The Red Flour Beetle, Tribolium Castaneum, Sharath Chandra Gaddelapati, Smitha George, Anilkumar Moola, Karthi Sengodan, Subba Reddy Palli

Entomology Faculty Publications

Histone acetylation, a crucial epigenetic modification, is governed by histone acetyltransferases (HATs), that regulate many biological processes. Functions of HATs in insects are not well understood. We identified 27 HATs and determined their functions using RNA interference (RNAi) in the model insect, Tribolium castaneum. Among HATs studied, N-alpha-acetyltransferase 40 (NAA40) knockdown caused a severe phenotype of arrested larval development. The steroid hormone, ecdysone induced NAA40 expression through its receptor, EcR (ecdysone receptor). Interestingly, ecdysone-induced NAA40 regulates EcR expression. NAA40 acetylates histone H4 protein, associated with the promoters of ecdysone response genes: EcR, E74, E75, and HR3, and causes an increase …

The Mechanoreceptor Piezo Is Required For Spermatogenesis In Bombyx Mori, Zhongjie Zhang, Xiaojing Liu, Bo Hu, Kai Chen, Ye Yu, Chenxin Sun, Dalin Zhu, Hua Bai, Subba Reddy Palli, Anjiang Tan

Entomology Faculty Publications

Background The animal sperm shows high diversity in morphology, components, and motility. In the lepidopteran model insect, the silkworm Bombyx mori, two types of sperm, including nucleate fertile eupyrene sperm and anucleate unfertile apyrene sperm, are generated. Apyrene sperm assists fertilization by facilitating the migration of eupyrene spermatozoa from the bursa copulatrix to the spermatheca. During spermatogenesis, eupyrene sperm bundles extrude the cytoplasm by peristaltic squeezing, while the nuclei of the apyrene sperm bundles are discarded with the same process, forming matured sperm.

Results In this study, we describe that a mechanoreceptor BmPiezo, the sole Piezo ortholog in B. mori, …