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Development Of Cell-Penetrating Peptides Targeting Nuclear And Extra-Nuclear Signaling Pathways In Cancer Cells, Panthita Kaewjanthong

Chulalongkorn University Theses and Dissertations (Chula ETD)

Growth factors and hormones often mediate their biological effects through series of protein-protein interaction between cytoplasmic signaling molecules or transcription factors. Interfering of these protein-protein interactions has been shown to reduce or inhibit biological and growth responses to various growth factors and hormones. We previously demonstrated that progesterone receptor (PR) contains a polyproline domain (PPD) which directly interact to Src homology 3 (SH3) domain-containing molecules and expression of PR-PPD inhibits EGFR-mediated NSCLC cell proliferation. In this study, we investigated that the introduction of PR-PPD by cell-penetrating peptide could inhibit EGF-induced NSCLC cell proliferation. PR-PPD was attached to a cancer-specific CPP, …

ผลการปกป้องของสารสกัดใบรางจืดจากการเหนี่ยวนำความเป็นพิษด้วยกลูตาเมตในเซลล์ประสาท Ht-22 ผ่านวิถีออโตฟาจี, วุฒิพงษ์ วงศ์ทิพย์

Chulalongkorn University Theses and Dissertations (Chula ETD)

หนึ่งในสาเหตุสำคัญของการเกิดโรคความเสื่อมของระบบประสาทนั้นเกิดได้จากภาวะเครียดออกซิเดชันภายในเซลล์ประสาท โดยพบว่าสารสื่อประสาทชนิดกลูตาเมตเมื่อมีระดับสูงผิดปกติสามารถเหนี่ยวนำให้เกิดอนุมูลอิสระและภาวะเครียดออกซิเดชันนำไปสู่การสูญเสียและการตายของเซลล์ประสาทได้ โดยเฉพาะการตายของเซลล์จากการเกิดกระบวนการออโตฟาจีมากเกินไป ซึ่งเป็นกระบวนการที่มีบทบาทสำคัญในการควบคุมการตายของเซลล์ผ่านวิถีอื่นๆ รางจืด (Thunbergia laurifolia) เป็นพืชสมุนไพรไทยมีสรรพคุณในการถอนพิษ ต้านการอักเสบ และ ต้านอนุมูลอิสระได้ดี จุดประสงค์ในการวิจัยครั้งนี้ คือ ศึกษาคุณสมบัติการต้านอนุมูลอิสระของสารสกัดหยาบจากใบรางจืด และการปกป้องการตายของเซลล์ประสาทผ่านวิถีออโตฟาจี จากการเหนี่ยวนำภาวะเครียดออกซิเดชันด้วยกลูตาเมตโดยทดสอบในเซลล์ประสาทส่วนฮิปโปแคมปัสของหนูชนิด HT-22 ใบรางจืดถูกนำมาสกัดด้วยเอทานอล จากผลการทดสอบพบว่าสารสกัดหยาบจากใบรางจืดมีความสามารถในการต้านอนุมูลอิสระ และมีปริมาณสารประกอบ ฟลาโวนอยด์และฟีนอลิกสูง โดยจากการวิเคราะห์ด้วยเครื่อง LC-MS และเปรียบเทียบผลที่ได้กับฐานข้อมูล METLIN-(CA, USA) พบสารออกฤทธิ์สำคัญที่ยังไม่มีรายงานในสารสกัดเอทานอลของใบรางจืด ได้แก่ Apigenin 7-O-glucoside และ 7-Hydroxycoumarin ยิ่งไปกว่านั้นสารสกัดหยาบจากใบรางจืดยังสามารถลดการตายของเซลล์ประสาทจากการเหนี่ยวนำความเป็นพิษด้วยกลูตาเมต โดยสามารถยับยั้งการเกิดอนุมูลอิสระภายในเซลล์ และเพิ่มการแสดงออกของยีนต้านอนุมูลอิสระที่ทำหน้าที่สำคัญในกระบวนการต้านอนุมูลอิสระในร่างกาย ได้แก่ superoxide dismutase 1 และ 2 (SOD1 and SOD2) catalase (CAT) และ glutathione peroxidase (GPx) ซึ่งสัมพันธ์กับการลดการเกิดกระบวนการออโตฟาจีภายในเซลล์และเพิ่มปริมาณ ไมโตคอนเดรียโปรตีน โดยพบว่าสารสกัดหยาบจากใบรางจืดสามารถลดอัตราส่วนการแสดงออกของโปรตีน LC3B-II/LC3B-I และเพิ่มการแสดงออกของไมโตคอนเดรียโปรตีน TOM20 เมื่อทำการตรวจหาตำแหน่งที่จำเพาะต่อการแสดงออกของโปรตีนในกระบวนการออโตฟาจี (LC3B) และไมโตคอนเดรียด้วยกล้องจุลทรรศน์ชนิดคอนโฟคอล พบว่า สารสกัดหยาบจากใบรางจืดสามารถลดการเกิด LC3-puncta ซึ่งเป็นลักษณะเด่นของการเกิดกระบวนการออโตฟาจี นอกจากนี้สารสกัดหยาบจากใบรางจืดยังลดการ colocalization ของ LC3B และไมโตคอนเดรีย จากผลการศึกษานี้เราพบสารออกฤทธิ์สำคัญใหม่ที่ยังไม่มีรายงานมาก่อนของใบรางจืด โดยสารออกฤทธิ์นี้มีความสามารถในการปกป้องเซลล์ประสาทชนิด HT-22 จากภาวะเครียดออกซิเดชันและเป็นปัจจัยสำคัญทำให้สารสกัดจากใบรางจืดมีความสามารถลดการตายของเซลล์ประสาทผ่านวิถีออโตฟาจีได้ ซึ่งอาจสามารถนำไปพัฒนาเป็นสมุนไพรทางเลือกหรือยาเพื่อใช้ในการป้องกันหรือรักษาการเกิดโรคความเสื่อมของระบบประสาทได้ในอนาคต

Knob-Socket Investigation Of Stability And Specificity In Alpha-Helical Secondary And Quaternary Packing Structure, Taylor Renee Rabara

University of the Pacific Theses and Dissertations

The novel knob-socket (KS) model provides a construct to interpret and analyze the direct contributions of amino acid residues to the stability in α-helical protein structures. Based on residue preferences derived from a set of protein structures, the KS construct characterizes intra- and inter-helical packing into regular patterns of simple motifs. The KS model was used in the de novo design of an α-helical homodimer, KSα1.1. Using site-directed mutagenesis, KSα1.1 point mutants were designed to selectively increase and decrease stability by relating KS propensities with changes to α-helical structure. This study suggests that the sockets from the KS Model can …

Functional Analysis Of Bacillus Anthracis Aspartate Transcarbamoylase And Dihydroorotase, Katelyn Leigh Schwager Silva

Wayne State University Theses

There are many enzymes required for efficient and proper pyrimidine biosynthesis. The two that are most important and were discussed in this thesis are aspartate transcarbamoylase (ATCase) and dihydroorotase (DHOase). Both play an important role in not only pyrimidine biosynthesis production, but also mechanistic regulation of de novo synthesis. Anthrax is an infection caused by Bacillus anthracis. Here we studied ATCase and DHOase in Bacillus Anthracis. In this thesis we understood the effects of the enzymes ATCase and DHOase on pyrimidine biosynthesis. Adequate inhibitors of these enzymes would result in cell death and could pose as a cure to infection …

Eralpha Isoforms Modulate The Tumorigenicity Of 24r,25(Oh)2d3 In Estrogen-Responsive Cancer, Anjali Verma

Theses and Dissertations

Over 200,000 cases of breast cancer are diagnosed every year. Nearly 20% of these patients supplement their diets with some form of vitamin D. This high frequency of vitamin D supplement use may be due in part to research suggesting that cancer patients with higher serum vitamin D₃ levels have better prognoses than patients with low serum vitamin D_3. However, double-blind clinical trials on the efficacy of vitamin D₃ supplementation in breast cancer have been inconclusive. A recent meta-analysis showed evidence of reduced cancer recurrence in patients taking vitamin D₃ supplements who had ‘estrogen receptor positive’ …

Cyclophilin A As A Molecular Switch Regulating Prolactin Receptor Mediated Signaling, Mammary Tumorigenesis And Metastasis, Shawn Hakim

Theses and Dissertations

Prolactin (PRL) and its receptor (PRLr) have been implicated in the development and progression of human breast cancer. PRL activates its receptor and induces activation of proximal Janus kinase 2 (Jak2) for signal transduction. Here, we sought to determine the role of PRLr-associated peptidyl-prolyl isomerase, cyclophilin A (CypA), in modulating structure/function relationships of the PRLr. It was demonstrated that CypA mediated PRL-induced conformational change of the CFP- and -YFP tagged forms of the PRLr cytoplasmic-tail, whereas CypA inhibition by NIM811 (N-methyl-4-isoleucine cyclosporin) or knockdown blocked the conformational change of the PRLr assessed by Fluorescence Resonance Energy Transfer (FRET) signal or …

Preconditioning Of The Tumor Microenvironment By Means Of Low Dose Chemotherapies For An Effective Immunotherapy Of Breast Cancer, Hussein F. Aqbi

Theses and Dissertations

Breast cancer mortality is mainly due to distant recurrence of the disease arising from dormant tumor cells established by cancer therapies. Patients who initially respond to cancer therapies often succumb to distant recurrence of the disease. It is not clear why people with the same type of breast cancer respond to treatments differently; some escape from dormancy and relapse earlier than others. In addition, some tumor clones respond to immunotherapy while others do not. We investigated how autophagy plays a role in accelerating or delaying recurrence of neu overexpressing mouse mammary carcinoma (MMC) following adriamycin (ADR) treatment, and in affecting …

Electrostatic Networks And Mechanisms Of Δph-Dependent Gating In The Human Voltage-Gated Proton Channel Hv1, Ashley L. Bennett

Theses and Dissertations

The structure of the voltage-gated proton (H⁺) channel Hv1 is homologous to the voltage sensor domain (VSD) of tetrameric voltage-gated Na⁺, K⁺ and Ca²⁺ channels (VGCs), but lacks a pore domain and instead forms a homodimer. Similar to other VSD proteins, Hv1 is gated by changes in membrane potential (V), but unlike VGCs, voltage-dependent gating in Hv1 is modulated by changes in the transmembrane pH gradient (DpH = pH_o - pH_i). In Hv1, pH_o or pH_i changes shift the open probability (P_OPEN)-V relation by ~40 mV per …

Targeting Sphingosine Kinase 2 As A Treatment For Cholangiocarcinoma, Anthony D. Stillman

Theses and Dissertations

Cholangiocarcinoma (CCA) has a high mortality rate and its occurrence is rising. This increase prompts the need for improved CCA treatments. Studies have suggested that CCA is highly reliant on the sphingosine-1-phosphate-receptor-2 (S1PR2) and sphingosine kinase 2 (SphK2). Recently, a competitive SphK2 inhibitor, ABC294640, has been approved for clinical trial. ABC294640 has the potential to treat CCA, which is support by a phase I clinical study that was able to temporarily treat a patient suffering from metastasized CCA with ABC294640. To determine the viability of ABC294640 as a treatment for CCA, this study focused on determining the effects of ABC294640 …

An Investigation On The Role Of Β-Arrestin 2, Protein Kinase C And Sex On The Mechanism Of Morphine Tolerance In The Mouse Ileum, Karan Hitesh Muchhala

Theses and Dissertations

Opioids such as morphine are frequently used in the clinic to treat pain. However, the perennial bane of chronic opioid use is the rapid development of tolerance to the analgesic effects but delayed development of tolerance to the respiratory depressant and constipating effects. As constipation is one of the most common opioid-related adverse effects in humans, it is important to delineate mechanisms that drive opioid tolerance in the ileum and lack of it in the colon. The overarching goal of this thesis was to investigate mechanisms of morphine tolerance in the ileum by comparing the mechanism of morphine tolerance in …

Stat5b And Stat5 Tetramers Are Essential For Ige-Mediated Mast Cell Function, Kasalina N. Kiwanuka

Theses and Dissertations

Signal Transducers and Activators of Transcription (STATs) are latent transcription factors that mediate several cellular responses. This protein family consists of seven members, STAT1 – 6 including two closely related molecules, STAT5a and STAT5b, that show 96% amino acid sequence homology and are critical for lymphoid, myeloid and erythroid cell development and function. Activated STAT proteins dimerize and translocate to the nucleus, where they bind to high-affinity DNA motifs to modulate gene expression. We recently identified STAT5b as the critical regulator of IgE-mediated cytokine production in mast cells. STAT5b knockout (KO) cells show decreased sensitivity to IgE-mediated passive systemic anaphylaxis …

Adaptation Of The Streptococcal Collagen-Like Protein 1, Scl1, Of Group A Streptococcus To Recognize Fibronectin Type Iii Repeats, Dudley H. Mcnitt

Graduate Theses, Dissertations, and Problem Reports (ETD)

Background: Group A Streptococcus (GAS) is responsible more than 700 million infections worldwide each year. Most of these infections start with initial colonization of the throat and skin, which is augmented by surface adhesins. The streptococcal collagen-like protein 1 (Scl1) is a major adhesin expressed by GAS that contains an N-terminal sequence-variable (V) domain, protruded away from the cell surface by the collagen domain. The Scl-V domain is comprised of three pairs of anti-parallel α-helices interconnected by surface-exposed loops. For attachment, GAS adhesins require a portal of entry, such as a wound or breach in the epithelium, to enter …

Regulation Of The Long Non-Coding Rna Fam83h-As1 By Human Papillomavirus In Cervical Cancer, Jamie Ann Barr Ph.D.

Graduate Theses, Dissertations, and Problem Reports (ETD)

Non-coding RNAs (NcRNAs), such as long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), have been found to be involved in a variety of critical biological processes, and dysregulation of ncRNAs have been involved with several human diseases including cancer.

High-risk human papillomavirus (HPV) infection is one of the first events in the process of carcinogenesis in cervical and a subset of head and neck cancers. The expression of the viral oncoproteins E6 and E7 is essential in this process by inactivating the tumor suppressor proteins p53 and Rb, respectively, in addition to their interactions with other host proteins and regulation of …

Analysis Of Aboral Spine Variation In The Forcipulate Sea Star, Pisaster Ochraceus (Brandt 1835), Angela Jordane Jones

Cal Poly Humboldt theses and projects

Rocky intertidal zones are highly dynamic environments that exhibit substantial spatial and temporal variation in abiotic conditions, which can drive body form variation and energy allocation within calcifying species. Wave exposure, specifically, has been shown to be a significant driver of skeletal and structural morphology in organisms including gastropods, bivalves, and sponges. Many of such organisms, from sponges to echinoderms, rely on calcium carbonate for structural support and protection.

In the phylum Echinodermata (named for possessing a ‘spiny skin’), research on the form and function of calcium carbonate spines is largely relegated to Class Echinodea (e.g., urchins and sand dollars) …

Regulator Of G Protein Signaling-12 (Rgs12) In Dopaminergic And Kappa Opioid Receptor-Dependent Signaling And Behavior, Joshua David Gross

Graduate Theses, Dissertations, and Problem Reports (ETD)

Dopaminergic neurotransmission is critically involved in the etiology and treatment of many psychiatric and neurological disorders. One modulator of dopaminergic neurotransmission is the kappa opioid receptor (KOR) -- a G protein-coupled receptor (GPCR) that is densely expressed within dopaminergic neurons and circuits. GPCRs are tightly regulated by a variety of intracellular signaling molecules, including Regulator of G Protein Signaling (RGS) proteins. Canonically, RGS proteins act as GTPase accelerating proteins (GAPs) on GTP-bound Ga subunits following GPCR activation, thereby hastening the rate at which GPCR-mediated G protein signaling is terminated. However, some RGS proteins exhibit more complex mechanisms of action on …

The Evaluation Of The Rapidhittm 200 On Degraded Biological Samples, Alice Kim

Graduate Theses, Dissertations, and Problem Reports (ETD)

DNA (deoxyribonucleic acid) has become an integral part of forensic science in the last couple of decades since its discovery to this application by Alec Jeffreys. Although there have been many advances throughout the years, the time it takes to obtain a DNA profile using conventional methods in a laboratory setting is approximately 24 to 72 hours. Due to this length of time and the increase in demand for DNA testing, it has caused a tremendous amount of backlog throughout the country. In 2009, the FBI (Federal Bureau of Investigation) in collaboration with the US Department of Defense of Homeland …

Immunomagnetic Beads Coupled With Anti-Ph-20 Antibodies To Isolate Sperm From Dna Mixtures For Sexual Assault Kit Application, Kayla Becks

Graduate Theses, Dissertations, and Problem Reports (ETD)

Sexual Assault Kits (SAKs) account for a large portion of DNA mixture samples that are processed within a forensic laboratory, most commonly in the form of vaginal swabs. A typical vaginal swab from a SAK contains the female victim's epithelial cells and varying concentrations of sperm cells left by the perpetrator. The key to analyzing these types of samples is to separate the mixture into male and female fractions. As such, there is a demand to develop novel techniques that have the capability of recovering as much of the male fraction as possible, specifically in cases where there is a …

Ebullition Of Oxygen From Seagrasses Under Supersaturated Conditions, Matthew H. Long, Kevin Sutherland, Scott D. Wankel, David J. Burdige, Richard C. Zimmerman

OES Faculty Publications

Gas ebullition from aquatic systems to the atmosphere represents a potentially important fraction of primary production that goes unquantified by measurements of dissolved gas concentrations. Although gas ebullition from photosynthetic surfaces has often been observed, it is rarely quantified. The resulting underestimation of photosynthetic activity may significantly bias the determination of ecosystem trophic status and estimated rates of biogeochemical cycling from in situ measures of dissolved oxygen. Here, we quantified gas ebullition rates in Zostera marina meadows in Virginia, U.S.A. using simple funnel traps and analyzed the oxygen concentration and isotopic composition of the captured gas. Maximum hourly rates of …

Dinitrogen Fixation Across Physico-Chemical Gradients Of The Eastern Tropical North Pacific Oxygen Deficient Zone, C. R. Selden, M. R. Mulholland, P.W. Bernhardt, B. Widner, A. Macías-Tapia, Q. Ji, A. Jayakumar

OES Faculty Publications

The Eastern Tropical North Pacific Ocean hosts one of the world's largest oceanic oxygen deficient zones (ODZs). Hot spots for reactive nitrogen (N_r) removal processes, ODZs generate conditions proposed to promote N_r inputs via dinitrogen (N₂) fixation. In this study, we quantified N₂ fixation rates by ¹⁵N tracer bioassay across oxygen, nutrient, and light gradients within and adjacent to the ODZ. Within subeuphotic oxygen‐deplete waters, N₂ fixation was largely undetectable; however, addition of dissolved organic carbon stimulated N₂ fixation in suboxic (μmol/kg O₂) waters, suggesting that diazotroph communities are …

Impact Of Seasonal And Host-Related Factors On The Intestinal Microbiome And Cestode Community Of Sorex Cinereus And Sorex Monticola, Katelyn D. Cranmer

College of Graduate Studies: Theses & Dissertations

The intestinal microbiome of mammals plays a significant role in host health and response to environmental stimuli and can include both beneficial native bacteria as well as parasitic worms. In this study, I examined the intestinal cestode and bacterial communities of two closely related species of shrew, Sorex monticola and Sorex cinereus, over a six month period in 2016. Specimens were collected approximately every three weeks from May to October from the Sangre de Cristo Mountains in Cowles, New Mexico. A total of 79 shrews were prepared with the gastrointestinal tracts removed and flash-frozen in liquid nitrogen. An additional …

Characterisation Of Cholesterolcontaining Microparticles In Autoimmunity, Shuai Shuai Hu

Doctoral

In recent years, it has become apparent that sub-micron scale remnants of cells, called microparticles (MPs), are present in human circulation. MPs contain DNA, RNA, protein and lipids (such as cholesterol). Increased numbers of MPs are observed in autoimmune conditions such as Systemic Lupus Erythematosus (SLE) and Rheumatoid Arthritis (RA). This work aims to address the deficiency in the literature concerning MP cholesterol (MPC) by establishing reference values for MPC in a representative healthy population group, and by investigating the potential of MP cholesterol as a biomarker in autoimmunity.

Relationship Of Sociodemographic Factors With Serum Levels Of Vitamin D In A Healthy Population Of Pakistan, Khalida Iqbal, Najmul Islam, Naseema Mehboobali, Ali Asghar, Saleem Perwaiz Iqbal, Mohammad Perwaiz Iqbal

Department of Biological & Biomedical Sciences

High prevalence of vitamin D deficiency has been reported from Pakistan. Association of sociodemographic factors with vitamin D status has received little attention in this region. Therefore, we embarked on investigating the relationship of sociodemographic factors with vitamin D levels in a healthy Pakistani population. Venous blood from 226 healthy participants (age range 19-69 years) was collected and analyzed for serum concentrations of 25(OH) vitamin D [25(OH)D] and other related biomarkers. Demographic characteristics of the study participants were collected. Vitamin D deficiency (25(OH)D levels less than 20 ng/ml) was found to be 75% in this cohort. Gender, sunlight exposure and …

Naturally Derived Compounds As Preventatives Of Proteinopathies, Lois Mendez

Open Access Theses & Dissertations

Neurodegenerative diseases, such as Parkinson’s disease (PD), afflict millions worldwide. Of greater concern is the fact that a main risk factor this disease is aging and the baby boomer population is now reaching a geriatric age. Despite the active research in this area, little progress has been made in the development of therapeutic strategies and furthering of our understanding in pinpointing the causal events that onset these disease processes. Our lab has focused on studying the protein homeostasis of key biomarkers in neurodegenerative diseases and examining whether natural compounds can act as neuro-protectants and, thus, attenuate the pathology that ensues …

Computational Study Of Disease Related Proteins Form Electrostatic Point Of View, Chitra Bahadur Karki

Open Access Theses & Dissertations

In the last three decades, many giant DNA viruses have been discovered. The giant viruses present a unique and essential research frontier for the study of self-assembly and regulation of supramolecular assemblies. The question on how these giant DNA viruses assemble thousands of proteins so accurately to form their protein shell, the capsids, remains largely unanswered. Revealing the mechanisms of giant virus assembly will help to discover the mysteries of many self-assembly biology problems. Paramecium Bursaria Chlorella Virus 1 (PBCV-1) is one of the most intensively studied giant viruses. Based on the high-resolution structure of PBCV-1, we implemented a multi-scale …

Novel Methods For The Inactivation Of Cruzain For The Prevention And Treatment Of Chagas Disease, Veronica Gonzalez

Open Access Theses & Dissertations

Chagas Disease, also known as American Trypanosomiasis, is endemic to Latin American and is gradually making its way to other countries. The disease is caused by Trypanosoma cruzi, a protozoan parasite that causes lesions and inflammation of organs including the heart, esophagus, and colon. Over 30% of people infected will develop heart disease which can be fatal if untreated. While no vaccine is yet available, research is currently being conducted in finding new treatments for the disease. One target is an enzyme that is believed to help the progression of the disease. Cruzain, a cysteine protease expressed as a pro-enzyme, …

Non Linear Optics For Materials Fabrication And Medical Instrumentation, Aurelio Paez

Open Access Theses & Dissertations

Two-photon absorption is a nonlinear optical process where two photons are absorbed by a molecule simultaneously. The probability of this quantum phenomenon is proportional to the quadratic excitation of light intensity. It has many applications in biomedical and materials research, such as two-photon fluorescence microcopy. The first project is to apply two-photon absorption induced bond cleavage in photoreactive materials for engineering 3D tissue scaffolds. The major challenge for growing thick 3D tissues is the lack of vasculature, where nutrients and oxygen can be delivered to the growing cells. Our collaborators have synthesized a novel polypeptide that is composed of 34-mer …

Potential Of Nanoscale Elements To Control Fusarium Wilt Disease In Tomato (Solanum Lycopersicum), Enhance Macronutrient Use Efficiency, And Increase Its Yield, Ishaq Olarewaju Adisa

Open Access Theses & Dissertations

Nanotechnology has a great potential in ensuring food production, security and safety globally. Over the past decade, research on the use of nanomaterials to supply nutrient elements and protect plants from pest and diseases has significantly increased. Tomato (Solanum lycopersicum) is one of the most consumed vegetables in the world and United State is one of its largest producers globally generating billions of dollars annually in revenue.. Tomato plants are affected worldwide by Fusarium wilt caused by Fusarium oxysporum f. sp. Lycopersici. There is growing concern about excessive use of conventional pesticides in controlling Fusarium and other diseases in tomato …

Identification Of Antibiotic Ge37468a From Pseudonocardia Symbionts Of Trachymyrmex Septentrionalis Ants, Krithika Rao

Scripps Senior Theses

In response to the growing rates of antibiotic resistance in human bacterial pathogens, this study explores the natural products involved in the defensive symbiosis between actinobacteria and fungus-growing ants to uncover new potential antibiotics. This study also seeks to understand the function of natural antibiotics in their ecological contexts, especially those involved in defensive symbioses. Defensive symbiosis can be a beneficial platform for discovering useful antibiotics, because antibiotics in these relationships must be able to selectively inhibit enemies without harming hosts, and are therefore likely more specific and less toxic. Pseudonocardia sp. associated with Trachymyrmex septentrionalis ants demonstrated antibiotic activity …

Functional Characterization Of Accessory Proteins And Novel Activities In Direct And Indirect Trna Aminoacylation, Udumbara Menike Rathnayake

Wayne State University Dissertations

Indirect tRNA aminoacylation is essential for most bacteria and archaea, particularly when these species do not have genes encoding asparaginyl- and/or glutaminyl-tRNA synthetase (AsnRS and GlnRS). In the absence of AsnRS, the first step in Asn-tRNAAsn synthesis involves misacylation of tRNAAsn with aspartate to produce Asp-tRNAAsn; this reaction is catalyzed by a non-discriminating aspartyl-tRNA synthetase (ND-AspRS). Subsequently, in bacteria, an amidotransferase called GatCAB converts Asp-tRNAAsn to Asn-tRNAAsn. An analogous, two-step processes exist to produce Gln-tRNAGln. In this case, a non-discriminating glutamyl-tRNA synthetase (ND-GluRS) misacylates tRNAGln to produce Glu-tRNAGln, which is then converted to Gln-tRNAGln by GatCAB. The central hub of …

Limited Sequence Diversity Within A Population Supports Prebiotic Rna Reproduction, Ryo Mizuuchi, Niles Lehman

Chemistry Faculty Publications and Presentations

The origins of life require the emergence of informational polymers capable of reproduction. In the RNA world on the primordial Earth, reproducible RNA molecules would have arisen from a mixture of compositionally biased, poorly available, short RNA sequences in prebiotic environments. However, it remains unclear what level of sequence diversity within a small subset of population is required to initiate RNA reproduction by prebiotic mechanisms. Here, using a simulation for template-directed recombination and ligation, we explore the effect of sequence diversity in a given population for the onset of RNA reproduction. We show that RNA reproduction is improbable in low …