Download or read book Sexual Differentiation of Malaria Parasites is Controlled by Unique Epigenomic and Proteomic Cascades as Revealed by Comparative Functional Genome Analyses written by Nanika Coetzee and published by . This book was released on 2017 with total page 250 pages. Available in PDF, EPUB and Kindle. Book excerpt: There is a continuous and urgent need for novel antimalarial agents with new modes of action due to P. falciparum resistance development against most of the currently used therapeutics. In the search for a novel class of antimalarial, the identification of a novel target, preferably present in both the asexual and sexual gametocyte stages, is essential. P. falciparum gametocytes develop due to the irreversible binary choice of a minor proportion of asexual parasites to commit to sexual differentiation. This process is characterised by essential morphological, physiological and biochemical changes to prepare the terminally differentiated mature gametocytes for transmission to the mosquito. It is therefore undeniably important to target these transmissible stages using chemotherapeutic interventions that, in context of limiting resistance development, should be exploited by means of novel drug targets. However, the complexity of gametocytogenesis and the stage-specific developmental decisions is not fully understood and this impedes the discovery of essential molecular players that can be targeted in intervention strategies. In this project, stage-specific gametocytogenesis was studied at the level of epigenome regulation through quantitative chromatin proteomics, mirrored by evaluation of the dynamics in the global quantitative proteome during this differentiation process. Ultimately, the information obtained with these global evaluation strategies informed analyses of novel inhibitors that target the parasite’s epigenetic gene regulation machinery. Gene expression in Plasmodia integrates post-transcriptional and translational regulation with epigenetic marking of active genomic regions through histone post-translational modifications (PTMs). To generate insights into the importance of histone PTMs to the parasite’s entire asexual and sexual developmental cycles, we used comparative quantitative chromatin proteomics to identify and functionally characterise eight distinct P. falciparum life cycle stages. Various novel histone PTMs and stage-specific histone PTM profiles were identified, with histone PTM combinations classified for the first time in P. falciparum. Gametocytes were enriched for a specific set of histone PTMs that is involved in stage-specific differentiation. This stage-specific differentiation was subsequently also observed in a global comparative quantitative proteome evaluation of gametocytogenesis. Protein abundance profiles and functional annotation of protein sets led to the description of enriched biological processes during stage-specific gametocyte development. Interestingly, gametocyte sex differentiation was shown to be characterised by key molecular players very early on during development, and genes previously identified as translationally repressed were shown here to be directly involved in gametocyte development. The importance of chromatin level regulation and its observed effect on the proteome dynamics during gametocytogenesis led to the proposal that these essential processes could be targeted with intervention strategies. We discovered compounds with limited cross-resistance and potent multi-stage activity against asexual parasites, early and late stage gametocytes by targeting the parasite’s epigenetic regulation. Collectively, this thesis presents the most complete and comparative chromatin proteomic and global proteomic analyses of the entire stage-specific P. falciparum development, providing insights into the intricacies characterising Plasmodial developmental biology, specifically during gametocytogenesis. The data importantly prove that novel epigenetic regulatory mechanisms identified in this study can be targeted with chemotherapeutic interventions, overcoming current resistance mechanisms and contribute to malaria elimination strategies.

Download or read book Integrative Transcriptome and Phenome Analysis Reveals Unique Regulatory Cascades Controlling the Intraerythrocytic Asexual and Sexual Development of Human Malaria Parasites written by RieÌ8tte Andele̹ Van Biljon and published by . This book was released on 2019 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: The Plasmodium falciparum parasite, the major causative agent of malaria on the African continent, has evolved numerous cellular adaptations to effectively propagate its species. The parasite can proliferate asexually, producing mass amounts of progeny to subsist in the human host or differentiate into sexual forms (gametocytes) that, once mature, can transmit to a feeding Anopheles mosquito. Key to our ability to effectively develop chemical candidates that interfere with either of these processes is the identification and understanding of critical factors that regulate parasite development. This is particularly true for the development of antimalarials that can be used in malaria elimination strategies by targeting both parasite proliferation and transmission. We therefore hypothesized that parasite proliferation and differentiation use divergent mechanisms for gene expression that could be observed through a thorough investigation of the functional genome of these different parasite forms. This doctoral study therefore set out to increase our knowledge base on three crucial aspects of parasite development: 1) the atypical cell cycle that allows the rapid proliferation of asexual parasites; 2) the full molecular profile of gametocytogenesis enabling the cellular differentiation that allows the parasite to transmit; and 3) the metabolic differences between these proliferating and differentiating parasites that results from their strategy-specific mechanisms of developmental control. The atypical cell cycle of the parasite, associated with the massive cell number expansion in asexual development, is notoriously difficult to study. Here, we contributed a novel system by developing a cell cycle synchronization tool that reversibly blocks the development of asexual parasites at the G1/S transition. This results in an inescapable arrest of the cell cycle that is completely and functionally reversible; parasites re-initiate cell cycle progression and continue to S phase within 6 h. This system provided the opportunity to characterize cell cycle phases in the parasite and additionally evaluate molecular mechanisms associated with cell cycle arrest or re-initiation. During cell cycle arrest, the parasite enters a quiescent state reminiscent of a mitogen-activated restriction point. This arrest is unique and solely attributed to the removal of the specific mitogens within this system, polyamines. These analyses indicate the close interaction between transcriptional regulation and signal transduction cascades in the progression through the parasite℗þs cell cycle and for the first time highlight aspects of controlled cell cycle regulation in Plasmodium. In contrast to proliferation, the process of sexual differentiation only started receiving attention in the past few years. As such, we lack fundamental understanding of the mechanisms driving the unique gametocyte differentiation of P. falciparum parasites. This study contributes a detailed analysis of gametocyte differentiation that revealed distinct developmental transitions demarcating the start of gametocytogenesis, intermediate gametocyte development and finally maturation to produce the transmissible mature gametocytes. The study provides evidence for coordinated regulation of gene expression on a transcriptional level. We propose a model for regulation of gametocytogenesis in malaria parasites that involves active repression of gene sets mediated through epigenetics and RNA destabilization as well as active transcription of gene sets through successive ApiAP2 transcription factor activity. This data provides the most detailed framework of coordinated gene regulation events underlying development of P. falciparum gametocytes to date, a unique resource for the malaria community. The comprehensive and complex transcriptional regulation described for the proliferation and differentiation of the parasite led us to evaluate the functional consequence thereof. A whole cell phenotype microarray system was evaluated for its ability to measure the metabolic processes that define asexual and sexual stage metabolism as a functional consequence of changed gene expression profiles during proliferation and differentiation. The study provided metabolic profiles detailing carbon and nitrogen metabolism in asexual parasites, mature and immature gametocyte stages. The data highlighted dipeptide metabolism as a distinguishing feature in mature gametocytes and showed the presence of a low, delayed metabolic state concurrent with reduced transcriptional activity observed in this stage. These results show that gene expression changes associated with differentiation compared to proliferation translate to an observable metabolic phenotype and that transcriptional regulation shapes the molecular landscape underlying crucial events that enable the parasite℗þs intraerythrocytic asexual and sexual development.

Download or read book Integrative Transcriptome and Phenome Analysis Reveals Unique Regulatory Cascades Controlling the Intraerythrocytic Asexual and Sexual Development of Human Malaria Parasites written by Ri tte Andel Van Biljon and published by . This book was released on 2019 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: The Plasmodium falciparum parasite, the major causative agent of malaria on the African continent, has evolved numerous cellular adaptations to effectively propagate its species. The parasite can proliferate asexually, producing mass amounts of progeny to subsist in the human host or differentiate into sexual forms (gametocytes) that, once mature, can transmit to a feeding Anopheles mosquito. Key to our ability to effectively develop chemical candidates that interfere with either of these processes is the identification and understanding of critical factors that regulate parasite development. This is particularly true for the development of antimalarials that can be used in malaria elimination strategies by targeting both parasite proliferation and transmission. We therefore hypothesized that parasite proliferation and differentiation use divergent mechanisms for gene expression that could be observed through a thorough investigation of the functional genome of these different parasite forms. This doctoral study therefore set out to increase our knowledge base on three crucial aspects of parasite development: 1) the atypical cell cycle that allows the rapid proliferation of asexual parasites; 2) the full molecular profile of gametocytogenesis enabling the cellular differentiation that allows the parasite to transmit; and 3) the metabolic differences between these proliferating and differentiating parasites that results from their strategy-specific mechanisms of developmental control. The atypical cell cycle of the parasite, associated with the massive cell number expansion in asexual development, is notoriously difficult to study. Here, we contributed a novel system by developing a cell cycle synchronization tool that reversibly blocks the development of asexual parasites at the G1/S transition. This results in an inescapable arrest of the cell cycle that is completely and functionally reversible; parasites re-initiate cell cycle progression and continue to S phase within 6 h. This system provided the opportunity to characterize cell cycle phases in the parasite and additionally evaluate molecular mechanisms associated with cell cycle arrest or re-initiation. During cell cycle arrest, the parasite enters a quiescent state reminiscent of a mitogen-activated restriction point. This arrest is unique and solely attributed to the removal of the specific mitogens within this system, polyamines. These analyses indicate the close interaction between transcriptional regulation and signal transduction cascades in the progression through the parasite s cell cycle and for the first time highlight aspects of controlled cell cycle regulation in Plasmodium. In contrast to proliferation, the process of sexual differentiation only started receiving attention in the past few years. As such, we lack fundamental understanding of the mechanisms driving the unique gametocyte differentiation of P. falciparum parasites. This study contributes a detailed analysis of gametocyte differentiation that revealed distinct developmental transitions demarcating the start of gametocytogenesis, intermediate gametocyte development and finally maturation to produce the transmissible mature gametocytes. The study provides evidence for coordinated regulation of gene expression on a transcriptional level. We propose a model for regulation of gametocytogenesis in malaria parasites that involves active repression of gene sets mediated through epigenetics and RNA destabilization as well as active transcription of gene sets through successive ApiAP2 transcription factor activity. This data provides the most detailed framework of coordinated gene regulation events underlying development of P. falciparum gametocytes to date, a unique resource for the malaria community. The comprehensive and complex transcriptional regulation described for the proliferation and differentiation of the parasite led us to evaluate the functional consequence thereof. A whole cell phenotype microarray system was evaluated for its ability to measure the metabolic processes that define asexual and sexual stage metabolism as a functional consequence of changed gene expression profiles during proliferation and differentiation. The study provided metabolic profiles detailing carbon and nitrogen metabolism in asexual parasites, mature and immature gametocyte stages. The data highlighted dipeptide metabolism as a distinguishing feature in mature gametocytes and showed the presence of a low, delayed metabolic state concurrent with reduced transcriptional activity observed in this stage. These results show that gene expression changes associated with differentiation compared to proliferation translate to an observable metabolic phenotype and that transcriptional regulation shapes the molecular landscape underlying crucial events that enable the parasite s intraerythrocytic asexual and sexual development.

Download or read book Molecular Parasitology written by Julia Walochnik and published by Springer. This book was released on 2016-10-20 with total page 546 pages. Available in PDF, EPUB and Kindle. Book excerpt: In the past years, genome projects for numerous human parasites have been completed and now allow first in depth comparisons and evolutionary conclusions. The genomes of parasites reflect the coevolution with their host, metabolic capacities depending on their respective habitat in the host. Gut parasites usually have an anaerobic metabolism, while blood parasites have an aerobic metabolism, intracellular parasites escape the immune system, while extracellular parasites evade the immune system, usually by antigenic variation. Comprehensive genome data now being available allow us to address profound scientific questions, such as which traits enable the parasite to survive in the human host, which to cause disease and which can be used as drug targets. This book intends to give an overview of the state of knowledge on “the molecules” of protozoan parasites – on their genomes, proteomes, glycomes and lipidomes.

Download or read book Toxoplasma Gondii written by Louis M. Weiss and published by Academic Press. This book was released on 2013-08-10 with total page 1109 pages. Available in PDF, EPUB and Kindle. Book excerpt: This 2e of Toxoplasma gondii reflects the significant advances in the field in the last 5 years, including new information on the genomics, epigenomics and proteomics of T. gondii as well as a new understanding of the population biology and genetic diversity of this organism. T. gondii remains the best model system for studying the entire Apicomplexa group of protozoans, which includes Malaria, making this new edition essential for a broad group of researchers and scientists. Toxoplasmosis is caused by a one-celled protozoan parasite known as T. gondii. The infection produces a wide range of clinical syndromes in humans, land and sea mammals, and various bird species. Most humans contract toxoplasmosis by eating contaminated, raw or undercooked meat (particularly pork), vegetables, or milk products; by coming into contact with the T. gondii eggs from cat feces; or by drinking contaminated water. The parasite damages the ocular and central nervous systems, causing behavioral and personality alterations as well as fatal necrotizing encephalitis. It is especially dangerous for the fetus of an infected pregnant woman and for individuals with compromised immune systems, such as HIV-infected patients. Completely updated, the 2e presents recent advances driven by new information on the genetics and genomics of the pathogen Provides the latest information concerning the epidemiology, diagnosis, treatment and prevention of toxoplasmosis Offers a single-source reference for a wide range of scientists and physicians working with this pathogen, including parasitologists, cell and molecular biologists, veterinarians, neuroscientists, physicians, and food scientists

Download or read book Genes and Genomes written by R.S. Verma and published by Elsevier. This book was released on 1998-06-03 with total page 281 pages. Available in PDF, EPUB and Kindle. Book excerpt: The laws of inheritance were considered quite superficial until 1903, when the chromosome theory of heredity was established by Sutton and Boveri. The discovery of the double helix and the genetic code led to our understanding of gene structure and function. For the past quarter of a century, remarkable progress has been made in the characterization of the human genome in order to search for coherent views of genes. The unit of inheritance termed factor or gene, once upon a time thought to be a trivial an imaginary entity, is now perceived clearly as the precise unit of inheritance that has continually deluged us with amazement by its complex identity and behaviour, sometimes bypassing the university of Mendel's law. The aim of the fifth volume, entitled Genes and Genomes, is to cover the topics ranging from the structure of DNA itself to the structure of the complete genome, along with everything in between, encompassing 12 chapters. These chapters relate much of the information accumulated on the role of DNA in the organization of genes and genomes per se. Several distinguished scientists, all pre-eminent authorities in each field to share their expertise. Obviously, since the historical report on the double helix configuration in 1953, voluminous reports on the meteoric advances in genetics have been accumulated, and to cover every account in a single volume format would be a Herculean task. Therefore, only a few topics are chosen, which are of great interest to molecular geneticists. This volume is intended for advanced graduate students who would wish to keep abreast with the most recent trends in genome biology.

Download or read book Current Topics in Malaria written by Alfonso J. Rodriguez-Morales and published by . This book was released on 2016-11-30 with total page 508 pages. Available in PDF, EPUB and Kindle. Book excerpt:

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 Epigenetics of Infectious Diseases written by Walter Doerfler and published by Springer. This book was released on 2017-05-26 with total page 281 pages. Available in PDF, EPUB and Kindle. Book excerpt: The present volume of Epigenetics and Human Health is devoted to the patho-epigenetics of viral and microbial infections, an exiting new field of disease-related epigenetic research. As recognized during the past years, epigenetic reprogramming of pathogen and host genome functions – the latter frequently induced by pathogens – plays an important role in many infectious processes. Beyond their immediate relevance for pathogen proliferation and obligatorily associated symptoms, such alterations frequently contribute to severe additional complications, such as the development of immunodeficiency, cancer and various chronic disorders. This holds in particular for epigenetic dysregulation of host gene expression induced by latent infections. The present book summarizes current knowledge of the mechanisms underlying epigenetic changes caused by viral, bacterial, fungal and protozoan infections and their impact on human health.

Download or read book Drug Resistance in Leishmania Parasites written by Alicia Ponte-Sucre and published by Springer Science & Business Media. This book was released on 2012-09-04 with total page 458 pages. Available in PDF, EPUB and Kindle. Book excerpt: One of the main problems concerning therapeutic tools for the treatment of parasitic diseases, including leishmaniasis, is that some field parasites are naturally resistant to the classical drugs; additionally, current therapies may select parasites prone to be resistant to the applied drugs. These features are (at least partially) responsible for the disappointing persistence of the disease and resultant deaths worldwide. This book provides a comprehensive view of the pathology of the disease itself, and of parasitic drug resistance, its molecular basis, consequences and possible treatments. Scientists both from academic fields and from the industry involved in biomedical research and drug design, will find in this book a valuable and fundamental guide that conveys the knowledge needed to understand and to improve the success in combating this disease worldwide.

Download or read book Avian Malaria Parasites and other Haemosporidia written by Gediminas Valkiunas and published by CRC Press. This book was released on 2004-10-28 with total page 946 pages. Available in PDF, EPUB and Kindle. Book excerpt: When studying the effects of parasites on natural populations, the avian haematozoa fulfills many of the specifications of an ideal model. Featuring a multitude of tables and illustrations, Avian Malaria Parasites and Other Haemosporidia summarizes more than a century of research on bird haemosporidians. For a long time, bird blood parasites served as important models in studying human diseases. Although now largely replaced, the wealth of data and research remain. With chapters addressing life cycles and morphology, pathogenicity, ultrastructure, geographical distribution, and illustrated keys to all known species of the parasites, this book is a masterful assessment of the biology of bird haemosporidian parasites.

Download or read book The Social Biology of Microbial Communities written by Institute of Medicine and published by National Academies Press. This book was released on 2013-01-10 with total page 633 pages. Available in PDF, EPUB and Kindle. Book excerpt: Beginning with the germ theory of disease in the 19th century and extending through most of the 20th century, microbes were believed to live their lives as solitary, unicellular, disease-causing organisms . This perception stemmed from the focus of most investigators on organisms that could be grown in the laboratory as cellular monocultures, often dispersed in liquid, and under ambient conditions of temperature, lighting, and humidity. Most such inquiries were designed to identify microbial pathogens by satisfying Koch's postulates.3 This pathogen-centric approach to the study of microorganisms produced a metaphorical "war" against these microbial invaders waged with antibiotic therapies, while simultaneously obscuring the dynamic relationships that exist among and between host organisms and their associated microorganisms-only a tiny fraction of which act as pathogens. Despite their obvious importance, very little is actually known about the processes and factors that influence the assembly, function, and stability of microbial communities. Gaining this knowledge will require a seismic shift away from the study of individual microbes in isolation to inquiries into the nature of diverse and often complex microbial communities, the forces that shape them, and their relationships with other communities and organisms, including their multicellular hosts. On March 6 and 7, 2012, the Institute of Medicine's (IOM's) Forum on Microbial Threats hosted a public workshop to explore the emerging science of the "social biology" of microbial communities. Workshop presentations and discussions embraced a wide spectrum of topics, experimental systems, and theoretical perspectives representative of the current, multifaceted exploration of the microbial frontier. Participants discussed ecological, evolutionary, and genetic factors contributing to the assembly, function, and stability of microbial communities; how microbial communities adapt and respond to environmental stimuli; theoretical and experimental approaches to advance this nascent field; and potential applications of knowledge gained from the study of microbial communities for the improvement of human, animal, plant, and ecosystem health and toward a deeper understanding of microbial diversity and evolution. The Social Biology of Microbial Communities: Workshop Summary further explains the happenings of the workshop.

Download or read book Host Manipulation by Parasites written by David P. Hughes and published by Oxford University Press. This book was released on 2012-06-07 with total page 247 pages. Available in PDF, EPUB and Kindle. Book excerpt: Parasites that manipulate the behaviour of their hosts represent striking examples of adaptation by natural selection. This text provides an authoritative review of host manipulation by parasites that assesses developments in the field and lays out a framework for future research.

Download or read book Rodent Malaria written by R. Killick-Kendrick and published by Elsevier. This book was released on 2012-12-02 with total page 435 pages. Available in PDF, EPUB and Kindle. Book excerpt: Rodent Malaria reviews significant findings concerning malaria parasites of rodents, including their taxonomy, zoogeography, and evolution, along with life cycles and morphology; genetics and biochemistry; and concomitant infections. This volume is organized into eight chapters and begins by sketching out the history of the discovery of rodent as well as aspects of parasitology, immunology, and chemotherapy. These concepts are investigated two decades following Ignace Vincke's major discovery and Meir Yoeli's successful establishment of the method of cyclical transmission of the parasite. The following chapters focus on the taxonomy and systematics of the subgenus Vinckeia, with reference to the concepts of species and subspecies of animals and the degree to which they apply to malaria parasites, in particular to those of rodents. The discussion then shifts to how the rodent malaria parasites provide a unique insight into the subcellular organization of Plasmodium species, the use of rodent malaria as an experimental model to study immunological responses, and infectious agents that interact with malaria parasites. The book concludes with a chapter on malaria chemotherapy, with emphasis on the value of rodent malaria in antimalarial drug screening and the use of antimalarial drugs as biological probes. This book will be of interest to protozoologists and physicians as well as those from other disciplines including biochemistry, immunology, pharmacology, cell biology, and genetics.

Download or read book Jellyfish and Polyps written by Antonella Leone and published by MDPI. This book was released on 2020-11-20 with total page 230 pages. Available in PDF, EPUB and Kindle. Book excerpt: This Special Issue of Marine Drugs gathers recent investigations on the proteomes, metabolomes, transcriptomes, and the associated microbiomes of marine jellyfish and polyps, including bioactivity studies of their compounds and more generally, on their biotechnological potential, witnessing the increasingly recognized importance of Cnidaria as a largely untapped Blue Growth resource for new drug discovery. These researches evoke the outstanding ecological importance of cnidarians in marine ecosystems worldwide, calling for a global monitoring and conservation of marine biodiversity, so that the biotechnological exploitation of marine living resources will be carried out to conserve and sustainably use the natural capital of the oceans.

Download or read book Lifecycles of Pathogenic Protists in Humans written by Wanderley de Souza and published by Springer. This book was released on 2023-02-02 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume covers the most important parasitic protists that are known to infect humans. The pathogens discussed cause diseases like toxoplasmosis, malaria, cryptosporidiosis, leishmaniasis, amoebiasis, trichomoniasis, and giardiasis. Readers from microbiology will appreciate the special focus on protist cell biology. As demonstrated in several of the chapters, these parasites are characterized by peculiar structures and organelles that cannot be found in mammalian cells – even though both are eukaryotic. The book employs light and electron microscopy to display the changing morphology in various stages of parasitic development. In turn, the results are supplemented by transcriptome and proteome profiles that help to describe how these changes take place on a molecular level. Both researchers and clinicians from tropical medicine will find essential and practically applicable background information on these increasingly important pathogens.

Download or read book Insect Symbiosis Volume 3 written by Kostas Bourtzis and published by CRC Press. This book was released on 2008-10-28 with total page 444 pages. Available in PDF, EPUB and Kindle. Book excerpt: The associations between insects and microorganisms, while pervasive and of paramount ecological importance, have been relatively poorly understood. The third book in this set, Insect Symbiosis, Volume 3, complements the previous volumes in exploring this somewhat uncharted territory. Like its predecessors, Volume 3 illustrates how symbiosis resear