Download or read book Structure Function and Antibody mediated Inhibition of Plasmodium CelTOS a Protein that Enables Cell Traversal by Malaria Parasites written by John Rashid Jimah and published by . This book was released on 2017 with total page 142 pages. Available in PDF, EPUB and Kindle. Book excerpt: Malaria is an immense global health problem which is primarily caused by Plasmodium falciparum and Plasmodium vivax parasites. These parasites have a complex life cycle, with stages in the human host and mosquito vector, and traverse diverse host and vector cells. Cell traversal involves biological processes such as parasite motility, breaching of cell membranes, and immune evasion which are mediated by various Plasmodium proteins that are only now beginning to be identified. Genetic studies have implicated Plasmodium CelTOS (cell-traversal protein for ookinetes and sporozoites) in mediating the traversal of sporozoites through the mammalian liver sinusoidal layer and ookinetes through the mosquito midgut epithelium. Additionally, CelTOS is a promising malaria vaccine candidate, as immunization of mice with CelTOS elicits a protective humoral and cell-mediated immune response. An immune response to CelTOS in humans is also correlated with protection from malaria. Even though CelTOS has critical roles in Plasmodium biology and is a vaccine target, the molecular function and mechanism of CelTOS had been unknown, primarily due to its lack of sequence similarity to proteins of known function.In our studies, we investigated the biophysical function of CelTOS to gain insight into its role during cell traversal. We determined the structure of PvCelTOS and observed similarity to proteins that bind and disrupt cell membranes, including HIV-1 gp41 and the Mycobacterium toxin ESAT-6. The structural similarity of CelTOS to these proteins informed the hypothesis that CelTOS binds and disrupts host and vector cell plasma membranes to enable the exit of parasites out of invaded cells during traversal. Subsequent investigations revealed that CelTOS specifically binds phosphatidic acid, a lipid predominantly present within the inner leaflet of cell plasma membranes, and disrupts liposomes composed of this lipid by pore-formation. Furthermore, microinjection of CelTOS into Xenopus oocytes damaged the plasma membrane and resulted in leakage of the cytosol. Taken together, we have identified CelTOS as the first Plasmodium protein that enables the exit of malaria parasites from host and vector cells.Given that CelTOS enables the progression of parasites through stages in the mosquito vector and human host, it is a unique malaria vaccine candidate that may block both malaria transmission and infection. Immunization with CelTOS elicits antibodies that have been shown to inhibit malaria infection in mice. CelTOS antibodies also block ookinete development into oocysts, an important step in sporozoite development within mosquitoes. We investigated the mechanism of antibody-mediated inhibition of CelTOS by identifying the epitopes in CelTOS targeted by neutralizing and non-neutralizing antibodies. The crystal structures of CelTOS in complex with neutralizing antibodies delineate residues that are targeted by antibodies that block CelTOS-mediated membrane disruption. Identification of neutralizing epitopes in CelTOS will inform the design of immunogens that elicit potent neutralizing antibodies.In summary, our findings reveal CelTOS targets the inner leaflet of host and vector cell plasma membranes by pore formation which may enable the exit of parasites during cell traversal. Additionally, we have identified epitopes in Plasmodium CelTOS that are targeted by antibodies, which begins to elucidate the mechanism of antibody-mediated inhibition of CelTOS. These findings provide a foundation for exploring the biophysical mechanism of CelTOS including the mechanisms of lipid binding, membrane insertion, and oligomerization within membranes to form pores. Also, the approaches used in this study may be applied to elucidate the role of putative pore-forming proteins, such as SPECT2 and MAOP, which mediate other steps in cell traversal. Finally, by determining the structure of CelTOS and developing an in vitro method for testing CelTOS activity, this study will inform the design and screening of therapeutics and vaccines which target CelTOS to protect against malaria.

Download or read book Heat Shock Proteins of Malaria written by Addmore Shonhai and published by Springer Nature. This book was released on 2021-09-26 with total page 256 pages. Available in PDF, EPUB and Kindle. Book excerpt: This new edition describes the role of heat shock proteins in the life cycle of malaria parasites, particularly in the context of intracellular parasite stages. Thoroughly revised, this work provides a general introduction to the structural and functional features of heat shock proteins with a special focus on their role as molecular chaperones in ensuring protein quality control. The emphasis is on the heat shock protein families from Plasmodium falciparum, and their role in proteostasis and the development of malaria pathology. Moreover, the authors explore the latest prospects of targeting heat shock proteins in antimalarial drug discovery either directly or in combination therapies. Readers will experience a functional analysis of the individual families of heat shock proteins and their cooperation in functional networks, including both the parasite-resident proteome and the exportome released into host cells during intracellular stages. Subcellular and extracellular organelles such as the apicoplast and the Maurer’s Clefts associated with Plasmodium species are discussed in detail. The book highlights the role of heat shock proteins in the development and function of these structures. Biochemical expertise and the inclusion of novel therapeutic solutions make this collection a unique reference for experts in heat shock protein research, parasitology and infectious diseases, cell stress, molecular biology and drug discovery. Not least, advances in malaria control will contribute to ending epidemics and ensuring healthy lives in line with the UN Sustainable Development Goals.

Download or read book Molecular Mechanisms of Plasmodium Red Blood Cell Invasion written by Brian Michael Malpede and published by . This book was released on 2015 with total page 147 pages. Available in PDF, EPUB and Kindle. Book excerpt: The malaria parasite Plasmodium utilizes specialized proteins for adherence to cellular receptors in its mosquito vector and human host. Adherence is critical for parasite development, host cell traversal and invasion, and protection from vector and host immune mechanisms. These vital roles have identified several adhesins as vaccine candidates. A deficiency in current adhesin-based vaccines is induction of antibodies targeting non-conserved, non-functional, and decoy epitopes due to the use of full length proteins or binding domains. To alleviate the elicitation of non-inhibitory antibodies, conserved functional regions of proteins must be identified and exploited. Structural biology provides the tools necessary to achieve this goal, and has succeeded in defining biologically functional receptor binding and oligomerization interfaces for a number of promising malaria vaccine candidates. A critical step in the Plasmodium life cycle is adhesion to and invasion of erythrocytes by the merozoite during blood stage growth. The invasion process requires the formation of a tight junction between parasite adhesive proteins and red cell receptors. Formation of this junction allows the merozoite to engage and enter the red cell to form the parasitophorous vacuole. The Erythrocyte-binding-like (EBL) family of cellular adhesion proteins is implicated in the formation of this essential tight junction. Receptor binding by the EBL family of invasion ligands has been localized to a specific portion of each EBL protein designated Region II (RII). This region is composed of the Duffy- binding-like (DBL) domain, unique to Plasmodium species. The two Plasmodium species responsible for the majority of malaria disease in humans are P. falciparum and P. vivax. There are four identified EBL members in P. falciparum that contain two tandem DBL domains in RII. This organization contrasts the single DBL domain in RII of the only characterized EBL member of P. vivax, Duffy-binding Protein (PvDBP). Using a combination of structural, biophysical, and cellular interaction methods we examined the binding mode for these two Plasmodium EBL family members to define the molecular and mechanistic basis of unique red cell invasion routes. Specifically, we sought to enhance our understanding of the molecular and mechanistic details of invasion by Plasmodium EBL ligands with the ultimate goal of identifying novel targets for rational vaccination efforts. We examined receptor interactions of a P. falciparum EBL member, Erythrocyte-binding-antigen 140 (PfEBA-140) and P. vivax DBP to provide insight into invasion by both species of parasite. Our work identified unique interfaces on the DBL domain that provide specific recognition of each ligand's unique red blood cell receptor. Additionally, studies examining oligomeric state identified distinct mechanistic parameters for the two EBL ligands, and contrasted with the mechanism observed for another P. falciparum member, PfEBA-175.

Download or read book Molecular Mechanisms of Parasite Invasion written by Barbara A. Burleigh and published by Springer Science & Business Media. This book was released on 2008-12-05 with total page 255 pages. Available in PDF, EPUB and Kindle. Book excerpt: All of the parasitic organisms highlighted in this new book represent medically important human pathogens that contribute significantly to the global burden of disease. As such there is intense interest in understanding the molecular basis of infection by these pathogens—not only with regard to their clinical relevance but also the fascinating biology they reveal. For most of the parasites discussed here the ability to penetrate biological barriers and/or to establish intracellular residence is critical to survival of the pathogen in the mammalian hosts. For other parasites, a tissue invasive phenotype is a key virulence determinant. In the ensuing 18 chapters, select members of this diverse set of protozoan parasites, as well as some examples of the extremely reduced fungal parasites classified as Microsporidia, are discussed within the context of the fascinating molecular strategies employed by these organisms to migrate across biological barriers and to establish residence within target host cells.

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 Malaria written by Maria M. Mota and published by Springer. This book was released on 2017-01-12 with total page 275 pages. Available in PDF, EPUB and Kindle. Book excerpt: Currently, malaria kills more than 300,000 people per year, making it a top priority of world leaders and international organizations, who are working towards implementing and coordinating efforts to eradicate this disease. An effective malaria vaccine is recognized as the key element that will decide between success and failure in this fight. At present, despite intensive research efforts, such a vaccine is not yet available for use. However, there are a number of advanced candidate vaccines with high chances of success in the short term. Malaria: Immune Response to Infection and Vaccination provides a comprehensive view on the immune response to malaria and to the different vaccines under development. The book offers the following: - Contributions by top research leaders in the field, - Comparisons of the immune responses to both malaria infection and malaria vaccines, which are traditionally treated separately, - Coverage of the immune responses to the different stages of malaria, which are frequently treated as separate fields of research.

Download or read book Innovations and Implementations of Computer Aided Drug Discovery Strategies in Rational Drug Design written by Sanjeev Kumar Singh and published by Springer Nature. This book was released on 2021-02-02 with total page 334 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book presents various computer-aided drug discovery methods for the design and development of ligand and structure-based drug molecules. A wide variety of computational approaches are now being used in various stages of drug discovery and development, as well as in clinical studies. Yet, despite the rapid advances in computer software and hardware, combined with the exponential growth in the available biological information, there are many challenges that still need to be addressed, as this book shows. In turn, it shares valuable insights into receptor-ligand interactions in connection with various biological functions and human diseases. The book discusses a wide range of phylogenetic methods and highlights the applications of Molecular Dynamics Simulation in the drug discovery process. It also explores the application of quantum mechanics in order to provide better accuracy when calculating protein-ligand binding interactions and predicting binding affinities. In closing, the book provides illustrative descriptions of major challenges associated with computer-aided drug discovery for the development of therapeutic drugs. Given its scope, it offers a valuable asset for life sciences researchers, medicinal chemists and bioinformaticians looking for the latest information on computer-aided methodologies for drug development, together with their applications in drug discovery.

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 Encyclopedia of Malaria written by and published by Springer. This book was released on 2018-07-12 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: The Encyclopedia of Malaria represents a vast databank of information about the study of malaria. It provides an overview of the historical, rapid and significant developments that have occurred in malaria research, including the 2002 genome sequencing of Plasmodium falciparum and its mosquito vector, Anopheles gambiae. This work provides a concise source of up-to-date research findings in the form of definitions and essays and present comprehensive coverage of topics from history to findings to diagnosis and treatment, written by recognized malaria researchers with practical experience. It appeals to a diverse audience, including malaria researchers, teachers, investigators and public health professionals.

Download or read book Global Technical Strategy for Malaria 2016 2030 written by World Health Organization and published by World Health Organization. This book was released on 2015-11-04 with total page 35 pages. Available in PDF, EPUB and Kindle. Book excerpt: The World Health Organization's Global Technical Strategy for Malaria 2016- 2030 has been developed with the aim to help countries to reduce the human suffering caused by the world's deadliest mosquito-borne disease. Adopted by the World Health Assembly in May 2015 it provides comprehensive technical guidance to countries and development partners for the next 15 years emphasizing the importance of scaling up malaria responses and moving towards elimination. It also highlights the urgent need to increase investments across all interventions - including preventive measures diagnostic testing treatment and disease surveillance- as well as in harnessing innovation and expanding research. By adopting this strategy WHO Member States have endorsed the bold vision of a world free of malaria and set the ambitious new target of reducing the global malaria burden by 90% by 2030. They also agreed to strengthen health systems address emerging multi-drug and insecticide resistance and intensify national cross-border and regional efforts to scale up malaria responses to protect everyone at risk.

Download or read book The Anopheline Mosquito written by R. C. Dauglish and published by . This book was released on 1911 with total page 48 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book The Biochemistry of Parasites written by Federation of European Biochemical Societies. Meeting and published by Pergamon. This book was released on 1981 with total page 242 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Molecular Evolution of the Major Histocompatibility Complex written by Jan Klein and published by Springer Science & Business Media. This book was released on 2013-06-29 with total page 506 pages. Available in PDF, EPUB and Kindle. Book excerpt: From molecules to populations and back In biology, the most vigorous organisms often ensue from a union of two disparate, pure lines. In science, too, laws of hybrid vigor seem to operate at the interface between two disciplines, an interface that often proves to be fertile ground for germinating concepts and new outlooks. The fringes of research into the major histocompatibility complex (Mhc) have provided such an interface several times in the past and the encounters have invigorated fields such as transplantation biology, cellular immunology, and immunogenetics. In the last few years, a new interface has been emerging between Mhc and evolutionary genetics, and particularly the branch of evolutionary genetics dealing with molecular evolution. Mhc research relies upon molecular evolutionary genetics, with its grand superstructure of mathematical formulations, to come to grips with the events leading to and maintaining the Mhc polymorphism. Without the armament of rigorous statistical procedures developed by evolutionary geneticists, the intricate relationships among Mhc genes cannot be resolved. It will undoubtedly be a molecular geneticist who is the final arbiter in the dispute concerning the nature of the selection pressure molding the Mhc genes. And it is doubtful whether the true function of Mhc can ever be comprehended without the vantage point afforded by the elucidation of its evolutionary history.

Download or read book Fusion Protein Technologies for Biopharmaceuticals written by Stefan R. Schmidt and published by John Wiley & Sons. This book was released on 2013-01-28 with total page 995 pages. Available in PDF, EPUB and Kindle. Book excerpt: The state of the art in biopharmaceutical FUSION PROTEIN DESIGN Fusion proteins belong to the most lucrative biotech drugs—with Enbrel® being one of the best-selling biologics worldwide. Enbrel® represents a milestone of modern therapies just as Humulin®, the first therapeutic recombinant protein for human use, approved by the FDA in 1982 and Orthoclone® the first monoclonal antibody reaching the market in 1986. These first generation molecules were soon followed by a plethora of recombinant copies of natural human proteins, and in 1998, the first de novo designed fusion protein was launched. Fusion Protein Technologies for Biopharmaceuticals examines the state of the art in developing fusion proteins for biopharmaceuticals, shedding light on the immense potential inherent in fusion protein design and functionality. A wide pantheon of international scientists and researchers deliver a comprehensive and complete overview of therapeutic fusion proteins, combining the success stories of marketed drugs with the dynamic preclinical and clinical research into novel drugs designed for as yet unmet medical needs. The book covers the major types of fusion proteins—receptor-traps, immunotoxins, Fc-fusions and peptibodies—while also detailing the approaches for developing, delivering, and improving the stability of fusion proteins. The main body of the book contains three large sections that address issues key to this specialty: strategies for extending the plasma half life, the design of toxic proteins, and utilizing fusion proteins for ultra specific targeting. The book concludes with novel concepts in this field, including examples of highly relevant multifunctional antibodies. Detailing the innovative science, commercial realities, and brilliant potential of fusion protein therapeutics, Fusion Protein Technologies for Biopharmaceuticals is a must for pharmaceutical scientists, biochemists, medicinal chemists, molecular biologists, pharmacologists, and genetic engineers interested in determining the shape of innovation in the world of biopharmaceuticals.

Download or read book State of the World s Vaccines and Immunization written by J. M. Maurice and published by World Health Organization. This book was released on 2009-07-20 with total page 204 pages. Available in PDF, EPUB and Kindle. Book excerpt: This casebook collects 64 case studies each of which raises an important and difficult ethical issue connected with planning, reviewing or conducting health-related research. The book's purpose is to contribute to thoughtful analysis of these issues by researchers and members of research ethics committees (REC's known in some places as ethical review committees or institutional review boards) particularly those involved with studies that are conducted or sponsored internationally. . This collection is envisioned principally as a tool to aid educational programs from short workshops on research.

Download or read book Genetic Control of Malaria and Dengue written by Zach N. Adelman and published by Academic Press. This book was released on 2015-10-15 with total page 487 pages. Available in PDF, EPUB and Kindle. Book excerpt: Genetic Control of Malaria and Dengue focuses on the knowledge, technology, regulation and ethics of using genetically modified mosquitoes to interrupt the transmission of important vector-borne diseases including Malaria. It contains coverage of the current state of knowledge of vector-borne diseases and how they are currently controlled; vaccine, drug and insecticide development; various strategies for altering the genome of mosquitoes in beneficial ways; and the regulatory, ethical and social environment concerning these strategies. For more than five decades, the prospect of using genetically-modified mosquitoes to control vector-borne disease transmission has been a purely hypothetical scenario. We simply did not have the technology or basic knowledge to be able to do it. With the explosion of field trials and potential interventions in development, Genetic Control of Malaria and Dengue provides a comprehensive overview of research in genetics, microbiology, virology, and ecology involved in the development and implementation of genetic modification programs for virus and disease control. This book is meant to provide a practical guide to researchers, regulators and the general public about how this technology actually works, how it can be improved, and what is still unknown. Includes coverage of vectorial capacity, critical to understanding vector-borne disease transmission Provides a summary of the concepts of both population suppression and population replacement Contains pivotal coverage of ethical and ecological ramifications of genetics-based control strategies

Download or read book The Vaccine Book written by Barry R. Bloom and published by Academic Press. This book was released on 2016-06-23 with total page 666 pages. Available in PDF, EPUB and Kindle. Book excerpt: The Vaccine Book, Second Edition provides comprehensive information on the current and future state of vaccines. It reveals the scientific opportunities and potential impact of vaccines, including economic and ethical challenges, problems encountered when producing vaccines, how clinical vaccine trials are designed, and how to introduce vaccines into widespread use. Although vaccines are now available for many diseases, there are still challenges ahead for major diseases, such as AIDS, tuberculosis, and malaria. This book is designed for students, researchers, public health officials, and all others interested in increasing their understanding of vaccines. It answers common questions regarding the use of vaccines in the context of a rapidly expanding anti-vaccine environment. This new edition is completely updated and revised with new and unique topics, including new vaccines, problems of declining immunization rates, trust in vaccines, the vaccine hesitancy, and the social value of vaccines for the community vs. the individual child’s risk. Provides insights into diseases that could be prevented, along with the challenges facing research scientists in the world of vaccines Gives new ideas about future vaccines and concepts Introduces new vaccines and concepts Gives ideas about challenges facing public and private industrial investors in the vaccine area Discusses the problem of declining immunization rates and vaccine hesitancy