Download or read book Exploring Regulators of Sexual Differentiation and Blood Stage Development in Malaria Parasites written by Joshua Rice and published by . This book was released on 2015 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: The recently discovered Apicomplexan AP2 (ApiAP2) family of proteins is the best-studied group of transcription factors in Plasmodium falciparum, the causative agent of human malaria. While different ApiAP2s have been recognized to regulate transcription in every stage of P. falciparum development, two of these proteins--PfAP2-G and PF14-0633--are of particular interest for their roles in gametocytogenesis and blood stage cytoadherence, respectively. The goals of this study were to observe the expression of AP2-G relative to gametocyte formation and to study the relationship between PF14_0633 expression and cytoadherence. In order to accomplish these goals, a green fluorescent protein tag was to be used to monitor the expression of AP2-G, while a glmS ribozyme tag was chosen to modulate levels of PF14_0633 expression. AP2-G was successfully tagged with GFP but transfection of multiple parasite lines proved ineffective, making phenotypic observation impossible. The process of tagging PF14_0633 is currently underway with early success, but time constraints have hindered the completion of this experiment.
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 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 World Malaria Report 2018 written by World Health Organization and published by World Health Organization. This book was released on 2019-02-12 with total page 210 pages. Available in PDF, EPUB and Kindle. Book excerpt: This year s report shows that after an unprecedented period of success in global malaria control progress has stalled. Data from 2015?2017 highlight that no significant progress in reducing global malaria cases was made in this period. There were an estimated 219 million cases and 435 000 related deaths in 2017. The World malaria report 2018 draws on data from 90 countries and areas with ongoing malaria transmission. The information is supplemented by data from national household surveys and databases held by other organizations.
Download or read book Malaria Parasites written by Andrew P. Waters and published by Caister Academic Press Limited. This book was released on 2004 with total page 578 pages. Available in PDF, EPUB and Kindle. Book excerpt: The completion of the Plasmodium falciparum genome sequence in late 2002 heralded a new era in malaria research. The search began in earnest for new drugs and vaccines to combat malaria, a disease which afflicts up to 500 million people worldwide and is responsible for the deaths of more than one million people each year. The new genomic data is aiding a greater understanding of the living parasite and its interaction with the insect vector and human host. In this book internationally renowned experts provide up-to-date reviews of the most important aspects of post-genomic malaria research. Topics covered include: the P. falciparum genome and model parasites, bioinformatics and genome databases, microsatellite analysis, analysis of chromosome structure, cell cycle to RNA polymerase I and II mediated gene expression, role of the nuclear genome, the parasite surface and cell biology, and much more. The book is essential to all researchers working in this highly topical field and is recommended reading for scientists in other areas of biology and medicine.
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 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 Malaria written by Institute of Medicine and published by National Academies Press. This book was released on 1991-02-01 with total page 312 pages. Available in PDF, EPUB and Kindle. Book excerpt: Malaria is making a dramatic comeback in the world. The disease is the foremost health challenge in Africa south of the Sahara, and people traveling to malarious areas are at increased risk of malaria-related sickness and death. This book examines the prospects for bringing malaria under control, with specific recommendations for U.S. policy, directions for research and program funding, and appropriate roles for federal and international agencies and the medical and public health communities. The volume reports on the current status of malaria research, prevention, and control efforts worldwide. The authors present study results and commentary on the: Nature, clinical manifestations, diagnosis, and epidemiology of malaria. Biology of the malaria parasite and its vector. Prospects for developing malaria vaccines and improved treatments. Economic, social, and behavioral factors in malaria control.
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 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 Malaria written by Dyann Fergus Wirth and published by . This book was released on 2017 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Malaria is a mosquito-borne disease caused by parasitic protozoa that belong to the genus Plasmodium. This disease imposes a significant global health burden, claiming the lives of several thousand children and pregnant women each day. Increasing antimalarial drug resistance and the complexity of the Plasmodium life cycle, among other factors, have made eradication difficult. Written and edited by experts in the field, this collection from Cold Spring Harbor Perspectives in Medicine examines the biology, pathology, and epidemiology of malaria, as well as ongoing efforts to treat infections and manage their spread. Contributors discuss the Plasmodium life cycle, focusing on the molecular mechanisms by which the various parasitic stages induce clinical symptoms, interact with the immune system, and lead to further transmission of malaria. They also explore topics such as the interaction between mosquito reproduction and Plasmodium development, epigenetic regulation of malaria-associated genes, and unique features of malaria in pregnant women (e.g., parity-dependent susceptibility) and describe how an improved understanding of these phenomena may lead to novel intervention strategies. The driving forces behind antimalarial drug resistance are covered, as is progress in developing an effective vaccine and controlling mosquito populations. This volume is therefore an essential reference for all scientists, clinicians, and public health professionals interested in understanding malaria and reducing its devastating effects.
Download or read book Malaria written by Irwin W. Sherman and published by Amer Society for Microbiology. This book was released on 1998-01 with total page 575 pages. Available in PDF, EPUB and Kindle. Book excerpt: Every 30 seconds a death is caused by Malaria. This book brings together recent advances in our understanding of the basic biology, genetics and pathogenesis of malaria, to facilitate the rapid generation of new insights and interventions. Each chapter is written by a leading expert(s), and serves as both a useful introduction to the area and a helpful set of references. Malaria: Parasite Biology, Pathogenesis and Protection is a useful entry point for graduate and medical students, scientists and individuals engaged in a subspecialty of Malaria research, as well as those who are simply interested in getting a grasp on the present status of this ever burgeoning public health problem.
Download or read book Survey of Antimalarial Drugs written by George Robert Coatney and published by . This book was released on 1953 with total page 344 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Biology of Blood Sucking Insects written by Mike Lehane and published by Springer Science & Business Media. This book was released on 2012-12-06 with total page 301 pages. Available in PDF, EPUB and Kindle. Book excerpt: Blood-sucking insects are the vectors of many of the most debilitating parasites of man and his domesticated animals. In addition they are of considerable direct cost to the agricultural industry through losses in milk and meat yields, and through damage to hides and wool, etc. So, not surprisingly, many books of medical and veterinary entomology have been written. Most of these texts are organized taxonomically giving the details of the life-cycles, bionomics, relationship to disease and economic importance of each of the insect groups in turn. I have taken a different approach. This book is topic led and aims to discuss the biological themes which are common in the lives of blood-sucking insects. To do this I have concentrated on those aspects of the biology of these fascinating insects which have been clearly modified in some way to suit the blood-sucking habit. For example, I have discussed feeding and digestion in some detail because feeding on blood presents insects with special problems, but I have not discussed respiration because it is not affected in any particular way by haematophagy. Naturally there is a subjective element in the choice of topics for discussion and the weight given to each. I hope that I have not let my enthusiasm for particular subjects get the better of me on too many occasions and that the subject material achieves an overall balance.
