Cell Biology Commons^™

Diversity In The Hla-I Recognition Of Hla-F Monoclonal Antibodies: Hla-F Or Hla-Ib Monospecific, Hla-E Or Hla-G Bispecific Antibodies With Or Without Hla-Ia Reactivity, Mepur Ravindranath, Narendranath Ravindranath, Carly Amato-Menker, Fatiha El Hilali, Edward J Filippone

Division of Nephrology Faculty Papers

Previous investigators have used various anti-HLA-F monoclonal antibodies (mAbs) to demonstrate that the tissue distribution of HLA-F is highly restricted. Notably, these mAbs differed in their immunodiagnostic capabilities. Specifically, mAbs Fpep1.1 and FG1 detected HLA-F intracellularly in B cells but not on the cell surface, whereas mAb 3D11 detected HLA-F on the cell surface. The presence of HLA-F on T cells was recognized by mAb FG1 but not by mAb Fpep1.1. mAb 3D11 detected HLA-F on the cell surface of activated B cells and on peripheral blood lymphocytes, but not on the normal cells. Importantly, mAb 3D11 revealed that HLA-F …

Oxidative Stress And Ion Channels In Neurodegenerative Diseases, Razan Orfali, Adnan Z. Alwatban, Rawan S. Orfali, Liz Lau, Noble Chea, Abdullah M. Alotaibi, Young-Woo Nam, Miao Zhang

Pharmacy Faculty Articles and Research

Numerous neurodegenerative diseases result from altered ion channel function and mutations. The intracellular redox status can significantly alter the gating characteristics of ion channels. Abundant neurodegenerative diseases associated with oxidative stress have been documented, including Parkinson’s, Alzheimer’s, spinocerebellar ataxia, amyotrophic lateral sclerosis, and Huntington’s disease. Reactive oxygen and nitrogen species compounds trigger posttranslational alterations that target specific sites within the subunits responsible for channel assembly. These alterations include the adjustment of cysteine residues through redox reactions induced by reactive oxygen species (ROS), nitration, and S-nitrosylation assisted by nitric oxide of tyrosine residues through peroxynitrite. Several ion channels have been directly …

Research Progress In High-Throughput Phenotype Testing Technology And Equipment For Engineering Cells Based On Microfluidics, Shuang Li, Xiaojie Guo, Haibo Chen, Sisi Chen, Xin Da, Zhenghui Li, Qinxiu Liu, Yi Wang, Xinhui Xing, Chong Zhang

Bulletin of Chinese Academy of Sciences (Chinese Version)

Engineering cells are a core component of green bio-manufacturing. The efficient testing and acquisition of engineering cells with the desired phenotype is a critical factor in the successful implementation of bio-manufacturing. In recent years, based on microfluidics technologies, non-culture type single-cell phenotype high-throughput test equipment and culture type phenotype high-throughput test equipment for the growth and metabolism of single cell in a bioreactor have been developed such as microdroplet and microchamber, realizing high-throughput, automated, miniaturized, and integrated testing of the phenotypes of engineering cells and providing a powerful tool for the breeding of engineering cells. This review systematically compiles the …

Research On Innovative Development Path And Policy Guarantee Of China’S Synthetic Biology Industry, Hongjun Geng, Chang Wang

Bulletin of Chinese Academy of Sciences (Chinese Version)

Synthetic biology is hailed as the third revolution in life sciences after the discovery of the DNA double helix structure and genomic technology, and is the core driving force for the leapfrog development of next-generation biomanufacturing and the future bioeconomy, opening up an opportunity window for the reshaping of the global manufacturing map. How to strategically position the synthesis biology industry and seize the strategic high ground in the industry is a core topic of interest for global science and technology powers and manufacturing powers. Based on the identification of problems in the development of China’s synthesis biology industry, this …

Recent Progress And Perspectives On Development Of Gene Editing Tools, Zixian Liu, Chengping Li, Gogo Jun-Jie Liu

Bulletin of Chinese Academy of Sciences (Chinese Version)

The gene editing field has witnessed remarkable advancements in recent years, leading to the establishment and refinement of multidimensional gene editing platforms. These innovations have enabled precise targeted gene knockout, repair, and insertion. These tools have stimulated significant progress in fundamental research, therapeutics, agriculture, environment protection, and industrial applications. In this review, we provide a comprehensive overview of the milestones in gene editing tool development and offer perspectives on potential future directions for this rapidly evolving field.

Digitalized Design Of Cell Factory Enables Green Biomanufacturing, Fanze Meng, Rui Cao, Bing Hu, Lei Qin, Chun Li

Bulletin of Chinese Academy of Sciences (Chinese Version)

Green manufacturing is a modern manufacturing mode in the consideration of both environmental impact and efficiency of resource utilization, it represents a significant component of the “new productive force”. Centered on cell factories, green biomanufacturing leverages renewable resources to efficiently produce products that conform to the concepts of low-carbon, green, and sustainable development. The design of high-performance cell factories is pivotal for achieving efficient green biomanufacturing. Nevertheless, traditional cell factory design processes are complex, time-consuming, and labor-intensive. With advancements in artificial intelligence, digital-assisted cell factory design has emerged as a solution to save time and reduce costs. By integrating technologies …

Making The Connection: How Membrane Contact Sites Have Changed Our View Of Organelle Biology, G. Voeltz, E. Sawyer, G. Hajnóczky, W. Prinz

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The view of organelles and how they operate together has changed dramatically over the last two decades. The textbook view of organelles was that they operated largely independently and were connected by vesicular trafficking and the diffusion of signals through the cytoplasm. We now know that all organelles make functional close contacts with one another, often called membrane contact sites. The study of these sites has moved to center stage in cell biology as it has become clear that they play critical roles in healthy and developing cells and during cell stress and disease states. Contact sites have important roles …

Tail-Tape-Fused Virion And Non-Virion Rna Polymerases Of A Thermophilic Virus With An Extremely Long Tail, Anastasiia Chaban, Leonid Minakhin, Ekaterina Goldobina, Brain Bae, Yue Hao, Sergei Borukhov, Leena Putzeys, Maarten Boon, Florian Kabinger, Rob Lavigne, Kira S Makarova, Eugene V Koonin, Satish K Nair, Shunsuke Tagami, Konstantin Severinov, Maria L Sokolova

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Thermus thermophilus bacteriophage P23-45 encodes a giant 5,002-residue tail tape measure protein (TMP) that defines the length of its extraordinarily long tail. Here, we show that the N-terminal portion of P23-45 TMP is an unusual RNA polymerase (RNAP) homologous to cellular RNAPs. The TMP-fused virion RNAP transcribes pre-early phage genes, including a gene that encodes another, non-virion RNAP, that transcribes early and some middle phage genes. We report the crystal structures of both P23-45 RNAPs. The non-virion RNAP has a crab-claw-like architecture. By contrast, the virion RNAP adopts a unique flat structure without a clamp. Structure and sequence comparisons of …

Microstructure-Based Modeling Of Primary Cilia Mechanics, Nima Mostafazadeh, Andrew Resnick, Y.-N. Young, Zhangli Peng

Physics Faculty Publications

A primary cilium, made of nine microtubule doublets enclosed in a cilium membrane, is a mechanosensing organelle that bends under an external mechanical load and sends an intracellular signal through transmembrane proteins activated by cilium bending. The nine microtubule doublets are the main load-bearing structural component, while the transmembrane proteins on the cilium membrane are the main sensing component. No distinction was made between these two components in all existing models, where the stress calculated from the structural component (nine microtubule doublets) was used to explain the sensing location, which may be totally misleading. For the first time, we developed …

Fused In Sarcoma Regulates Glutamate Signaling And Oxidative Stress Response, Chiong-Hee Wong, Abu Rahat, Howard C Chang

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Mutations in fused in sarcoma (fust-1) are linked to ALS. However, how these ALS causative mutations alter physiological processes and lead to the onset of ALS remains largely unknown. By obtaining humanized fust-1 ALS mutations via CRISPR-CAS9, we generated a C. elegans ALS model. Homozygous fust-1 ALS mutant and fust-1 deletion animals are viable in C. elegans. This allows us to better characterize the molecular mechanisms of fust-1-dependent responses. We found FUST-1 plays a role in regulating superoxide dismutase, glutamate signaling, and oxidative stress. FUST-1 suppresses SOD-1 and VGLUT/EAT-4 in the nervous system. FUST-1 also regulates synaptic AMPA-type glutamate receptor …

Thymidine Phosphorylase Is A Promising Target In Sars-Cov-2 Spike Protein-Enhanced Thrombosis, Renat Roytenberg

Theses, Dissertations and Capstones

Thrombosis, as an underlying mechanism in cardiovascular diseases, is the leading global cause of death in the 21st century. Infection is a risk factor for thrombosis, and the coronavirus disease 2019 (COVID-19) pandemic has led to a rise in the incidence of thrombosis, thereby increasing mortality. In comparison to previous severe coronavirus outbreaks, rates of thrombosis in COVID-19 have been unprecedented. COVID-19 is caused by the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The SARS-CoV-2 spike protein (SP), the key used to enter host cells, is implicated in thrombosis pathology, though mechanisms are not fully understood. The SARS-CoV-2 …

The Effects Of Bisphenol S On Glial Cells Of The Peripheral Nervous System, Madeline Solomon, Rachael Sennett, Angela Asirvatham

Student Research Poster Presentations 2024

Schwann cells are glial cells in the peripheral nervous system that maintain nerve function and myelination. Peripheral nerve myelination is dependent on intact Schwann cell proliferation. Schwann cell proliferation can be adversely affected by environmental pollutants such as Bisphenol A (BPA). BPA is an endocrine-disrupting chemical found in plastic water bottles, receipt paper, containers, and many everyday products. Studies on BPA exposure showed that it stimulated cellular proliferation in neural stem cells. A commonly used manufactured derivative of BPA, Bisphenol S (BPS), has posed similar concerns. Previous research has found that BPS promotes the proliferation of MCF-7 breast cancer cells …

The Effects Of Bpf On Rt4 Schwannoma Cancer Cells, Rachael Sennett, Madeline Solomon, Angela Asirvatham

Student Research Poster Presentations 2024

Bisphenol A is a harmful compound common in plastics that causes negative health and environmental effects. Due to these effects, new guidelines have been made to limit exposure to BPA. However, modified versions of these compounds, including Bisphenol-F, are being used as a replacement. Exposure to BPF, which is comparable in structure to BPA, has similar effects as BPA on many organ systems with some being unknown. As there is not much known about BPF, especially in the peripheral nervous system, the aim of this research is to analyze proliferation rates in BPF-treated Schwann cells. It was hypothesized that with …

Assessing The Role Of Kmt2b Knockdown In Rhabdoid Tumorigenesis Utilizing Crispri, Karah Edmonds, Andrea Florian Phd

Science University Research Symposium (SURS)

An aggressive blood cancer commonly observed in pediatric patients, Mixed Lineage Leukemia (MLL), has a regulatory MLL complex that promotes histone methyltransferation. Modifying histones utilizing histone methyltransferases like KMT2B (MLL2), is essential for gene expression by regulating transcription. Loss of function and inhibition of KMT2B leads to dysregulation of transcription and therefore promotes MLL tumorigenesis. To improve cancer-targeted therapies, we will use CRISPR interference (CRISPRi) to knock down the expression of KMT2B and measure levels of Rhabdoid tumor cell proliferation and apoptosis. Previous research surrounding the MLL complex suggests that decreased expression of KMT2B will lead to increased levels of …

A New Model For Polar Growth In Mycobacteria: The Role Of Wag31 And Mmpl3 In Cell Wall Synthesis, Neda Habibi Arejan

Biology Dissertations - Archive

The disease Tuberculosis (TB) is caused by the pathogen Mycobacterium tuberculosis and was the cause of over one million deaths worldwide in 2023 (World Health Organization, 2023). TB treatment is difficult due to antibiotic tolerance and emerging resistance in Mtb strains. Mycobacterial cells have different regulatory mechanisms that allow them to adjust to myriad environmental stressors: these responses often lead to antibiotic tolerance. Therefore, studying responses to stress will lead to insights about antibiotic tolerance and treatment failure. Here, we specifically study two essential mycobacterial proteins, Wag31 and MmpL3, involved in cell wall metabolism. We show that Wag31 has distinct …

Osteohistological Assessment Of Edmontosaurus Radii From The Liscomb Bonebed, Prince Creek Formation, North Slope, Alaska, Emma Griffin

Student Research Poster Presentations 2024

Hadrosaurs were one of the most diverse dinosaur groups in the Late Cretaceous period and are known for their numerous articulated skeletons and monodominant bonebeds (Wosik et al., 2020). They are more commonly known as duck-billed dinosaurs and are found globally including latitudinal extremes such as the artic and Antarctica. Edmontosaurus, a genus of hadrosaur, are herbivores and are very large growing up to 8,000 pounds. Edmontosaurus were known to travel in herds as a defense mechanism and were one of the last non-avian dinosaurs living during the late Campanian stage through the end of the Maastrichtian stage, right up …

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 …

The Effects Of Secretion Regulators, Α-Synuclein And Cysteine String Protein-Α, In Thrombosis And Hemostasis, Alexis N. Smith

Theses and Dissertations--Molecular and Cellular Biochemistry

Platelets play many critical roles in the vasculature ensuring proper hemostasis and maintaining vascular integrity. They can mediate these different processes via the release of different cargo molecules from granules. Cargo release from the granules is mediated by a family of proteins called Soluble NSF Attachment Protein Receptors (SNAREs). This process is complex and is regulated by several protein-protein interactions that are not completely characterized. SNARE chaperones have been identified for the t-SNAREs such as Munc18b/STXBP2 for Syntaxin-11, but none have been identified for the VAMPs and SNAP proteins. Proteins of interest as potential chaperones for VAMPs and SNAP proteins …

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) …

Corals In Crisis: A Transcriptomic Investigation Of Stony Coral Tissue Loss Disease, Kelsey M. Beavers

Biology Dissertations - Archive

Coral reefs face existential threats due to climate change and human activities. The combined effects of ocean warming, overfishing, pollution, and habitat destruction have fundamentally altered the functionality of coral reefs and are driving a drastic increase in the prevalence and severity of coral disease outbreaks. Stony coral tissue loss disease (SCTLD) has emerged one of the most devastating disturbances to Caribbean reef ecosystems on record. Despite notable progress, the cellular mechanisms driving SCTLD pathogenesis remain poorly understood. To address this issue, my dissertation investigates the gene expression, histopathology, immune protein activity, and symbiont community dynamics involved in SCTLD progression …

Multiple Variables Influence The Finely Calibrated Antioxidant Defenses Of Clostridioides Difficile, Erin B. Purcell

Chemistry & Biochemistry Faculty Publications

The obligate anaerobe Clostridioides difficile encodes multiple reductases to detoxify molecular oxygen and reactive oxygen species. Caulat and colleagues have characterized the activity and regulation of four such reductases (L. C. Caulat, A. Lotoux, M. C. Martins, N. Kint, et al., mBio 15:e01591-24, 2024, https://doi.org/10.1128/mbio.01591-24). Each proved critical for clostridial survival in a different range of oxygen concentrations; together, they ameliorate a broad range of oxidative stress levels. Moreover, two previously uncharacterized regulators were found to control reductase gene expression in response to oxidative stress. The genetic repressor Rex and the reductase FdpF are both sensitive to the NAP …

Reprogramming Of Rat And Human Hepatoma Cells With Fibroblast-Specific Transcription Factors Msx1 And Pura, Merve Diler

Masters Theses

Despite all cells within an organism sharing the same genetic information, they develop into different tissues, each with a distinct gene expression profile required for tissue specialization. Understanding gene expression and the processes that regulate the expression, is crucial for understanding cell differentiation and tissue specialization, as these procedures are governed by unique gene expression and regulation patterns.

Whole genome microarray analyses identified several candidate genes that may be coding important transcription factors that play role in fibroblast identity such as Prrx1, Snai2, Shox2, Twist1, c-Fos, Msx1, Pdx1 (Idx1) and Pura (Pur1). The goal of this project is to determine …

Sphingosine Kinase 2 Depletion Dysregulates Hepatic Redox Metabolism And Enhances Inflammation In Early Metabolic Dysfunction-Associated Steatohepatitis (Mash), Kaitlyn Georgene Jackson

Theses and Dissertations

Metabolic dysfunction-associated steatotic liver disease (MASLD) currently affects one in three people worldwide; its prevalence is growing alongside other cardiometabolic disorders. Aberrations to redox and sphingolipid metabolism contribute to MASLD pathologic progression. Sphingosine-1-phosphate (S1P) is an active lipid, meaning that S1P participates in biochemical processes within the cell. S1P is generated by two distinct isoenzymes, sphingosine kinase (SphK)1 and SphK2. The localization of the SphK enzyme dictates S1P function. While cytosolic SphK1-generated S1P is well-characterized, nuclear and mitochondrial SphK2-generated S1P is less known. Moreover, SphK2 depletion effects on cellular redox processes and inflammation are not well-defined.

This study defines the …

Assessing Lipid Composition Of Cell Membrane In Escherichia Coli Under Aerobic And Anaerobic Conditions, Isabelle Johnson

Undergraduate Theses, Professional Papers, and Capstone Artifacts

Escherichia coli is a highly studied model organism that is tightly tied to the mammalian gastrointestinal system. This microorganism has the capability to be a beneficial gut microbe or a life-threatening pathogen. In this study, the lipid membrane of Escherichia coli was investigated using Matrix-Assisted Laser Desorption/Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MS) to observe the change in its composition in aerobic and anaerobic conditions. Evidence of desaturation was discovered in the spectra, though more investigation is needed to understand the metabolic processes and drives that result in this change. Elucidation of these pathways in the future could result in …

Elucidation Of Mismatch Repair Regulation By Abl1: Advantages/Disadvantages Of Tyrosine Kinase Inhibitor Treatment, Hannah Daniels

Theses and Dissertations--Toxicology and Cancer Biology

DNA mismatch repair (MMR) is a critical repair process necessary for not only repairing mispairs incorporated into the DNA during replication, but also for inducing apoptosis in response to certain types of DNA damage. MMR is required for maintaining genomic integrity and due to the importance of this pathway, any impairment of its function can lead to increased mutation frequency, which is well known to be a driving force of cancer development, progression, and resistance. Despite extensive studies involving the proteins involved in the MMR pathway, the regulation of those proteins remains relatively unknown. Regulation of MLH1, a protein necessary …

Kif3a Tail Domain Phosphorylation Is Not Required For Ciliogenesis In Mouse Embryonic Fibroblasts, Ayoola Fasawe, Jessica M. Adams, Martin Engelke

Faculty Publications – Biological Sciences

Primary cilia are essential signaling organelles that protrude from most cells in the body. Heterodimeric kinesin-2 (KIF3A/KIF3B/KAP3) powers several intracellular transport processes, including intraflagellar transport (IFT), essential for ciliogenesis. A long-standing question is how a motor protein is differentially regulated for specific cargos. Since phosphorylation of the KIF3A tail domain was suggested to regulate the activity of kinesin-2 for ciliogenesis, similarly as for the cytosolic cargo N-Cadherin, we set out to map the phosphosites involved in this regulation. Using well-characterized Kif3a−/−; Kif3b−/− mouse embryonic fibroblasts, we performed ciliogenesis rescue assays with a library of phosphomimetic mutants comprising all …

Functional Analyses Of The Polycomb-Group Genes In Sea Lamprey Embryos Undergoing Programmed Dna Loss, Cody Saraceno

Theses and Dissertations--Biology

During early embryonic development, the sea lamprey (Petromyzon marinus) undergoes programmatic elimination of DNA from somatic progenitor cells in a process termed programmed genome rearrangement (PGR). Eliminated DNA eventually becomes condensed into micronuclei, which are then physically degraded and permanently lost from the cell. Previous studies indicated that many of the genes eliminated during PGR have mammalian homologs that are bound by polycomb repressive complex (PRC) in embryonic stem cells. To test whether PRC components play a role in the faithful elimination of germline-specific sequences, we used a combination of CRISPR/Cas9 and lightsheet microscopy to investigate the impact …

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 …