Download or read book Probing Translational Regulation by the Malaria Parasite Plasmodium falciparum written by Christine Moore Sheridan and published by . This book was released on 2018 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book An Exploration of Transcriptional Regulation in the Human Malaria Parasite Plasmodium Falciparum written by Xueqing Lu and published by . This book was released on 2017 with total page 211 pages. Available in PDF, EPUB and Kindle. Book excerpt: Approximately half of the world's population is at risk of malaria transmission, and this number can be expected to grow as drug resistant strains continue to develop. Among the human infectious Plasmodium species, Plasmodium falciparum causes the most severe and lethal form of malaria. This parasite has an extreme AT-rich genome and a complex life cycle that is likely to be regulated by coordinate changes in gene expression. However, the mechanisms behind this fine-tuned gene expression and regulation system remain elusive. For instance, only a limited number of transcription factors have been identified. Recent studies suggest that epigenetic and post-transcriptional regulation may be used as alternative regulation strategies to compensate for the lack of transcription factors in this parasite. Therefore, in this dissertation work, we further explored the transcriptome, epigenome, and the proteome to better understand the transcriptional mechanisms in P. falciparum. In chapter 1, we demonstrated that genes are usually defined by unique nucleosomal features and that nucleosome landscape alone could be used to identify novel genes in organisms with a nucleotide bias. Next, we investigated nascent RNA expression profiles and observed that the majority of genes are transcribed at the trophozoite stage in response to the open chromatin structure of that stage. These results helped us link chromatin reorganization events to transcriptional activity and highlighted the importance of epigenetic and post-transcriptional regulation in this parasite. Therefore, in the latter two chapters, we further examined the proteasome and transcriptome isolated from both nuclear and cytoplasmic fractions to identify potential chromatin regulators. As a result, we identified a large number of chromatin-associated proteins and lncRNAs that are likely to have important roles in chromatin regulation and post-transcriptional and translational regulations. Collectively, data and results from these studies will become stepping-stones for future malaria studies and further assist the identification of promising anti-malarial drug targets.

Download or read book Engineering Control of Eukaryotic Translation with Application to the Malaria Parasite Plasmodium Falciparum written by Stephen Jacob Goldfless and published by . This book was released on 2014 with total page 130 pages. Available in PDF, EPUB and Kindle. Book excerpt: Experimenter control of target gene expression is a fundamental component of molecular biology research. In many systems, tools exist that allow generalizable control of gene expression at the transcriptional or post-transcriptional level. Plasmodium falciparum, the protozoan parasite responsible for the majority of death and sickness due to malaria, remains challenging to manipulate in the laboratory. No robust and generalizable tool for gene expression control has been developed in the parasite. To address this need, we engineered a new system for control of protein translation in eukarvotes, and applied it to P. falciparum. This system is based on the ligand-regulated interaction between an RNA aptamers and the TetR-repressor protein. Although such protein-RNA interactions are abundant in nature and are known to effectively mediate control of gene expression, our system is unique in its direct modulation by an exogenous chemical. By genetically encoding TetR-binding RNA aptamers in the 5' untranslated region (5'UTR) of an mRNA, translation of a downstream coding sequence is repressed by TetR in vivo and induced upon adding a non-toxic tetracycline analog. We first define the system's component molecular interactions in vitro, followed by optimization of the constituent parts for convenience and performance. We then further optimize the system and validate its performance in two model systems, the budding yeast Saccharomvces cerevisiae and cell-free rabbit reticulocyte extracts. We show the broad utility of the system in P. falciparum for controlling expression of reporter and endogenous proteins trafficked to a variety of subcellular compartments. Induction and repression are rapid and homogeneous across the cell population. Placing a drug resistance determinant tinder inducible control, we are able to modulate P. falciparum drug sensitivity, demonstrating the usefulness of the system for controlling relevant parasite biology. In the process of constructing and validating a novel tool for gene expression in P. falciparum. we built a new series of gene expression vectors for molecular biology work in the parasite. In addition to developing optimized protocols for plasmid construction, we built a standardized, sequence-defined family of plasmids for malaria research. In all, we present a generalizable, well-defined toolkit for genetic programming of P. falciparum.

Download or read book Translational Repression of the CPW WPC Multigene Family in the Malaria Parasite Plasmodium written by Pavitra Nagesh Rao and published by . This book was released on 2014 with total page 248 pages. Available in PDF, EPUB and Kindle. Book excerpt: The technical challenges of working with the sexual stages of the malaria parasite Plasmodium have hindered the characterization of putative parasite surface antigens in the quest for a successful malaria transmission-blocking vaccine. One such predicted uncharacterized extracellular protein, the CPW-WPC family of proteins, is conserved across Apicomplexa , and has been named for a characteristic domain that contains two conserved motifs CPxxW and WPC. We detected nine cpw-wpc transcripts in P. falciparum gametocytes and eight cpw-wpc transcripts in P. berghei gametocytes. With the exception of one cpw-wpc gene we observed no transcript expression in asexual stages. Using immune sera generated against a recombinant CPW-WPC protein, as well as a transgenic P. berghei parasite line expressing an epitope-tagged CPW-WPC protein, we were unable to detect protein expression in intraerythrocytic asexual and sexual stage parasites, suggesting translational control of some or all members of the family. RNA immunoprecipitation (RIP) followed by Reverse Transcriptase-PCR using transgenic DOZI::GFP and CITH::GFP-expressing P. berghei lines confirmed that all cpw-wpc transcripts were bound by both translational repressors in gametocytes, and thus likely translationally repressed until a later life cycle stage. In order to analyze translational repression in P. falciparum gametocytes the expression of luciferase reporters regulated by cpw-wpc and control regulatory regions was used as a proxy for CPW-WPC protein expression. This analysis demonstrated that cpw-wpc regulated transcripts were likely translationally silent in gametocytes but translationally activated following gametocyte activation.

Download or read book DNA Sequence Context and the Chromatin Landscape Differentiate Sequence specific Transcription Factor Binding in the Human Malaria Parasite Plasmodium Falciparum written by Victoria Bonnell and published by . This book was released on 2023 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Malaria, caused by protozoan parasites of the genus Plasmodium, remains a major global health burden, with 247 million cases and killing 619,000 in 2021 alone. In Plasmodium falciparum, the deadliest human malaria parasite, about 90% of the protein-coding genes are transcribed in a periodic fashion over the 48-hour intraerythrocytic development cycle (IDC), with the peak transcript abundance generally occurring just before the protein is required. The periodicity of transcription forms a genome-wide cascade of continuous gene expression, which is believed to be finely regulated by a limited number of transcriptional regulators, including the 30-member Apicomplexan APETALA2 (ApiAP2) family of sequence-specific transcription factors (TFs). Interestingly, this family of proteins has AP2 DNA-binding domains only evolutionarily conserved in plant-linage genomes and Apicomplexan parasites, making them potential drug targets for novel antimalarial therapeutics in humans. The current literature is focused only on identifying regulatory networks controlled by the ApiAP2 TFs; however, dissecting the molecular mechanisms of their genome-wide binding pattern is still understudied. Knowing mechanisms of binding site selection of putative drug targets is critical to identifying essential interactions or features to be blocked. This dissertation elucidates the biological function and binding specificity of a subset of ApiAP2 TFs, which each recognize similar DNA sequence motifs in vitro, along with their chromatin-remodeling interaction partners. This project applies in vitro, in vivo, and in silico approaches to identify how sequence preferences are established during parasite development by probing the effects of cis- and trans- regulation on TF binding, in addition to dissecting the function of these TFs in parasite development. In higher eukaryotes, TFs with similar binding preferences can carry out different regulatory functions in a given cell type, work synergistically or antagonistically, perform similar functions in different cell types, or can be fully redundant and only necessary in the event that the primary factor cannot function. The occurrence of multiple TFs recognizing similar DNA sequence motifs in P. falciparum is intriguing since functional gene redundancy is not often evolutionarily conserved in pathogens. Therefore, despite the similar DNA binding motifs of these proteins, we predict that they carry out distinct regulatory functions in the parasite. There are several established features investigated by this work that can modulate binding specificity of a TF such as: DNA sequence context/intrinsic DNA shape, interaction with cofactors, histone post-translational modification, and chromatin accessibility. It is critical to understand which features, or combinations thereof, influence binding specificity of transcriptional regulators in P. falciparum to inform future antimalarial drug development.

Download or read book World malaria report 2017 written by World Health Organization and published by World Health Organization. This book was released on 2018-02-12 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: The World Malaria Report 2017 presents a comprehensive state of play in global progress in the fight against malaria up to the end of 2016. It tracks progress in investments in malaria programs and research, malaria prevention, diagnosis and treatment, surveillance, trends in malaria disease burden, malaria elimination, and threats in tackling malaria and safeguarding the investments made. The report draws on data from 91 countries and areas with ongoing malaria transmission. The information is supplemented by data from national household surveys and databases held by other organizations. This year's report shows that after an unprecedented period of success in global malaria control, progress has stalled. In 2016, there were an estimated 216 million cases of malaria, an increase of about 5 million cases over 2015. Deaths reached 445,000, a similar number to the previous year.

Download or read book Apicomplexan Parasites written by Katja Becker and published by John Wiley & Sons. This book was released on 2011-01-19 with total page 548 pages. Available in PDF, EPUB and Kindle. Book excerpt: This handbook is the first dealing with the discovery of drugs directed against apicomplexan parasites. Amongst others, this group of endoparasites includes the causative agents of Malaria, Toxoplasmosis, and Babesiosis, the latter occurring mainly in animals. Written by renowned scientific experts from academia and industry, the book focuses on currentdrug development approaches for all apicomplexan diseases making it appealing to a large audience, ranging from research labs in academia to the human and veterinarian pharmaceutical industry. This work is the second volume of the new book series 'Drug Discovery in Infectious Diseases', edited by Prof. Dr Paul M. Selzer.

Download or read book Probing Intracellular Regulation written by Christian Neri and published by Bentham Science Publishers. This book was released on 2013-11-04 with total page 342 pages. Available in PDF, EPUB and Kindle. Book excerpt: Genome science or genomics is essential to advancing knowledge in the fields of biology and medicine. Specifically, researchers learn about the molecular biology behind genetic expression in living organisms and related methods of treating human genetic diseases (including gene therapy). Advances in Genome Science is an e-book series which provides a multi-disciplinary view of some of the latest developments in genome research, allowing readers to capture the essentiality and diversity of genomics in contemporary science. The second volume of this ebook series contains a selection of articles on intracellular gene regulation and expression in human disease such as arthritis, Alzheimer’s disease, Nijmegen Breakage Syndrome, Tumors and Malaria among other diseases. The volume also features some chapters on plant genetics

Download or read book Antimalarial Natural Products written by A. Douglas Kinghorn and published by Springer Nature. This book was released on 2022-01-02 with total page 116 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume begins with a short history of malaria and follows with a summary of its biology. It then traces the fascinating history of the discovery of quinine for malaria treatment, and then describes quinine’s biosynthesis, its mechanism of action, and its clinical use, concluding with a discussion of synthetic antimalarial agents based on quinine’s structure. It also covers the discovery of artemisinin and its development as the source of the most effective current antimalarial drug, including summaries of its synthesis and biosynthesis, its mechanism of action, and its clinical use and resistance. A short discussion of other clinically used antimalarial natural products leads to a detailed treatment of additional natural products with significant antiplasmodial activity, classified by compound type. Although the search for new antimalarial natural products from Nature’s combinatorial library is challenging, it is very likely to yield new antimalarial drugs. This book thus ends by identifying ten natural products with development potential as clinical antimalarial agents.

Download or read book The Malaria Genome Projects written by Irwin W. Sherman and published by World Scientific. This book was released on 2012 with total page 389 pages. Available in PDF, EPUB and Kindle. Book excerpt: The year 2012 marks the tenth anniversary of the announcement of the genome sequence of the human malaria parasite Plasmodium falciparum and that of its mosquito vector Anopheles. The genome sequences were a result of the Plasmodium falciparum Genome Project. This book covers in detail the biology of malaria parasites and the mosquitoes that transmit the disease, how the Genome Project came into being, the people who created it, and the cadre of scientists who are attempting to see the promise of the Project realized. The promise was: a more complete understanding of the genes of the parasite (and its vector) would provide a rational basis for the development of antimalarial drugs and vaccines, allow a better understanding of the regulation of the complex life cycle in the red blood and liver cells of the human, identify the genes the parasite uses to thwart the host immune response and the ways in which the parasite evades cure by drug treatments, as well as leading to more effective measures of control transmission. The hope was that cracking the genetic code of Plasmodium and Anopheles would reveal the biochemical Achilles heel of the parasite and its vector, leading to the development of novel drugs and better methods of control, and by finding the targets of protective immunity could result in the manufacture of effective vaccines. Through a historic approach, this book will allow for those new to the field, or those with insufficient background in the sciences, to have an easier entry point. Even scientists already working in the field may better appreciate how discoveries made in the past can impact the direction of future research.

Download or read book World Malaria Report 2019 written by World Health Organization and published by . This book was released on 2019-08-28 with total page 224 pages. Available in PDF, EPUB and Kindle. Book excerpt: The World Malaria Report 2019 provides a comprehensive update on global and regional malaria data and trends. The report tracks investments in malaria programs and research as well as progress across all intervention areas: prevention, diagnosis, treatment, elimination, and surveillance. It also includes dedicated chapters on the consequences of malaria on maternal infant and child health the "High Burden to High Impact" approach as well as biological threats to the fight against malaria. The 2019 report is based on information received from more than 80 countries and areas with ongoing malaria transmission. This information is supplemented by data from national household surveys and databases held by other organizations.

Download or read book Photochemistry written by Stefano Crespi and published by Royal Society of Chemistry. This book was released on 2021-09-20 with total page 507 pages. Available in PDF, EPUB and Kindle. Book excerpt: Providing critical analysis of emerging and well-established topics, this book is essential reading for anyone wanting to keep up to date with the literature on photochemistry and its applications. Volume 49 combines reviews on the latest advances in photochemical research with specific highlights in the field. The first section includes periodical reports of the recent literature on physical and inorganic aspects, including reviews of the molecules employed as dyes in art, light induced reactions in cryogenic matrices, photobiological systems studied by time-resolved infrared spectroscopy and photophysics, and photochemistry of transition metal complexes. This selection is completed by reviews of the literature on solar photocatalysis for water decontamination and disinfection and for water splitting/hydrogen production. Coverage continues in the second part with highlighted topics, from the use of aromatic carbonyls as photocatalysts and photoinitiators in synthesis, photoinduced and photocatalysed decarboxylation reactions, development of dye-sensitized solar cells, design of luminescent water-soluble systems, and applications of plasmonic nanoparticles. This volume also includes a third section entitled ‘SPR Lectures on Photochemistry’, where leading scientists in photochemistry provide examples to introduce a photochemical topic to academic readers, offering precious assistance to students in this field.

Download or read book Probing Photosynthesis written by Mohammad Yunus and published by CRC Press. This book was released on 2014-04-21 with total page 576 pages. Available in PDF, EPUB and Kindle. Book excerpt: Probing Photosynthesis represents the cutting edge of research on photosynthesis and provides details of experimental approaches that have been adopted to understand it's complex regulatory and adaptive processes. Its twenty seven chapters have been divided into four sections: Evolution, structure and function; Biodiversity metabolism and regulatio

Download or read book Malaria Immunology written by Peter Perlmann and published by Karger Medical and Scientific Publishers. This book was released on 2002-01-01 with total page 422 pages. Available in PDF, EPUB and Kindle. Book excerpt: Despite extensive efforts to control it, malaria is still one of the most devastating infectious diseases worldwide. This book, now in its second edition, provides a broad and up-to-date overview of the rapidly expanding field of malaria immunology and its importance in the control of this disease. The first section deals with the malaria parasite and its interactions with both the vertebrate host and the mosquitoes which transmit the disease. In the second part, the mechanisms of immunity and their regulation by environmental and genetic factors are discussed. Finally, this volume contains several chapters on malaria vaccine development, describing the application of the most recent vaccine technologies as well as ongoing and planned vaccine trials. Authored by well-recognized experts, this volume not only demonstrates the rapid progress being made in the search for vaccines against malaria, but also broadens our understanding of immunity to infection in general. It is therefore highly recommended reading for all scientists and professionals in the fields of immunology, infection and vaccine development.

Download or read book Essential Malariology written by Leonard Jan Bruce-Chwatt and published by John Wiley & Sons. This book was released on 1985 with total page 478 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book World Malaria Report 2015 written by World Health Organization and published by World Health Organization. This book was released on 2016-01-30 with total page 283 pages. Available in PDF, EPUB and Kindle. Book excerpt: The World Malaria Report 2015assesses global malaria disease trends and changes in the coverage and financing of malaria control programs between 2000 and 2015. It also summarizes progress towards international targets, and provides regional and country profiles that summarize trends in each WHO region and each country with malaria. The report is produced with the help of WHO regional and country offices, ministries of health in endemic countries, and a broad range of other partners. The data presented are assembled from the 96 countries and territories with ongoing malaria transmission, and a further five countries that have recently eliminated malaria. Most data are those reported for 2014 and 2015, although in some cases projections have been made into 2015, to assess progress towards targets for 2015.

Download or read book Advances in Malaria Research written by Deepak Gaur and published by John Wiley & Sons. This book was released on 2016-11-30 with total page 615 pages. Available in PDF, EPUB and Kindle. Book excerpt: Thoroughly reviews our current understanding of malarial biology Explores the subject with insights from post-genomic technologies Looks broadly at the disease, vectors of infection, and treatment and prevention strategies A timely publication with chapters written by global researchers leaders