Download or read book Plasmodium Falciparum Functional Genomics written by Jason Andrew Young and published by ProQuest. This book was released on 2007 with total page 384 pages. Available in PDF, EPUB and Kindle. Book excerpt: Malaria is a devastating disease that afflicts hundreds of millions of people worldwide each year. The recent availability of the genome sequence and several transcriptome and proteome datasets for Plasmodium falciparum, the agent responsible for the most lethal form of the disease, promises to accelerate the pace of malaria research. However, functional genomic methods must first be developed that are capable of converting the wealth of information contained within these large datasets into high-quality, testable hypotheses that lead to biologically relevant conclusions. For this purpose, we have developed functional genomic methods that use P. falciparum transcriptome datasets to elucidate malaria parasite gene function and transcriptional control mechanisms. First, I will describe a knowledge-based clustering algorithm we developed called Ontology-based Pattern Identification (OPI) that uses microarray-generated transcriptome data to rapidly predict gene function on a genome-wide basis. OPI analysis of transcriptome data from P. falciparum asexual, sporozoite, and high-purity stage I-V gametocytes using Gene Ontology annotations as a guide resulted in the identification of 381 functionally enriched gene clusters. These results shed light on the components of molecular mechanisms underlying parasite sexual development, as well as a multitude of other malaria parasite biological processes. Second, I will describe an algorithm we developed called Gene Enrichment Motif Searching (GEMS), designed specifically for the identification of cis -regulatory elements in the extremely AT-rich parasite genome. When applied to 21 OPI clusters, GEMS identified 34 putative cis -regulatory motifs associated with a variety of parasite processes including sexual development, cell invasion, antigenic variation and protein biosynthesis. These data, along with results from subsequent experimental characterization of several of these putative cis -regulatory elements using reporter gene assays, electrophoretic mobility shift assays, and DNA-affinity purification experiments suggest cis -regulatory element mediated transcriptional regulation plays an important role in the overall control of P. falciparum gene expression. The functional genomics approaches developed herein will aid to lay the groundwork for future research towards developing novel therapeutics against malaria.
Download or read book High Throughput Generation of P Falciparum Functional Molecules by Recombinational Cloning written by and published by . This book was released on 2004 with total page 8 pages. Available in PDF, EPUB and Kindle. Book excerpt: Large-scale functional genomics studies for malaria vaccine and drug development will depend on the generation of molecular tools to study protein expression. We examined the feasibility of a high-throughput cloning approach using the Gateway system to create a large set of expression clones encoding Plasmodium falciparum single-exon genes. Master clones and their ORFs were transferred en masse to multiple expression vectors. Target genes (n = 303) were selected using specific sets of criteria, including stage expression and secondary structure. Upon screening four colonies per capture reaction, we achieved 84% cloning efficiency. The genes were subcloned in parallel into three expression vectors: a DNA vaccine vector and two protein expression vectors. These transfers yielded a 100% success rate without any observed recombination based on single colony screening. The functional expression of 95 genes was evaluated in mice with DNA vaccine constructs to generate antibody against various stages of the parasite. From these, 19 induced antibody titers against the erythrocytic stages and three against sporozoite stages. We have overcome the potential limitation of producing large P. falciparum clone sets in multiple expression vectors. This approach represents a powerful technique for the production of molecular reagents for genome-wide functional analysis of the P. falciparum genome and will provide for a resource for the malaria resource community distributed through public repositories.
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 Exploration of Host Genetic Factors associated with Malaria written by Tabish Qidwai and published by Springer Nature. This book was released on 2021-03-08 with total page 174 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book is aimed to cover the role of genetic polymorphisms in human genes related to RBC disorders, metabolic enzymes, immune response, and cytoadherence in the susceptibility/resistance to malaria caused by Plasmodium falciparum. The chapters provide current information on the balancing trait and the significance of such traits in the malaria resistance. The book covers polymorphisms in the genes of the red blood cells-sickle cell anaemia; glucose-6-phosphate dehydrogenase deficiency and thalassemia that confer protection against malaria. In addition, the book explores selection of genetic variations in the human genome as genetic control mechanism against malaria in endemic regions. It also provides a comprehensive overview of the molecular epidemiology and natural selection of alleles in the genes which are associated with malaria, and presents description of the role of human genetic polymorphisms in malaria disease risk and disease outcome.
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 Parasite Genomics written by Luis M. de Pablos and published by Humana. This book was released on 2021-07-28 with total page 336 pages. Available in PDF, EPUB and Kindle. Book excerpt: This detailed book provides a comprehensive series of innovative research techniques and methodologies applied to the parasite genomics research area, all applying different approaches to analyzing parasite genomes and furthering the study of genetic complexity and the mechanisms of regulation. Beginning with chapters on novel sequencing and the bioinformatics pipeline, the volume continues by exploring diagnostic approaches using genomic tools, host-parasite interactions, as well as the genomics of parasite-derived extracellular vesicles. Written for the highly successful Methods in Molecular Biology series, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Parasite Genomics: Methods and Protocols creates a detailed picture of genomic approaches for researchers seeking a better understanding of characterizing parasite nucleic acid content.
Download or read book Advances in Malaria Research written by Deepak Gaur and published by John Wiley & Sons. This book was released on 2016-12-27 with total page 611 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
Download or read book The Application of Functional Genomics Systems Biology and Drug Development to the Study of Infectious Diseases written by Jingchun Zhu and published by . This book was released on 2006 with total page 360 pages. Available in PDF, EPUB and Kindle. Book excerpt: Genomics is creating a paradigm shift in the research of infectious diseases, transforming it from studying a few targets at a time to a genomic scale. We applied three genomic approaches to the study of malaria and its causative agents, a type of intracellular parasites belonging to the genus Plasmodium.
Download or read book Visualising Plasmodium Falciparum Functional Genomic Data in MaGnET written by Joanna Louise Sharman and published by . This book was released on 2009 with total page 280 pages. Available in PDF, EPUB and Kindle. Book excerpt: Malaria affects the lives of 500 million people around the world each year. The disease is caused by protozoan parasites of the genus Plasmodium, whose ability to evade the immune system and quickly evolve resistance to drugs poses a major challenge for disease control. The results of several Plasmodium genome sequencing projects have revealed how little is known about the function of their genes (over half of the approximately 5400 genes in Plasmodium falciparum, the most deadly human parasite, are annotated as hypothetical ). Recently, several large-scale studies have attempted to shed light on the processes in which genes are involved; for example, the use of DNA microarrays to profile the parasite s gene expression. With the emergence of varied types of functional genomic data comes a need for effective tools that allow biologists (and bioinformaticians) to explore these data. The goal of exploration/browsing-style analyses will typically be to derive clues towards the function of thus far uncharacterised gene products, and to formulate experimentally testable hypotheses. Graphic interfaces to individual data sets are obviously beneficial in this endeavour. However, effective visual data exploration requires also that interfaces to different functional genomic data are integrated and that the user can carry forward a selected group of genes (not merely one at a time) across a variety of data sets. Non-expert users especially benefit from workbenchlike tools offering access to the data in this way. Still, only very few of the contemporary publicly available software have implemented such functionality. This work introduces a novel software tool for the integrated visualisation of functional genomic data relating to P. falciparum: the Malaria Genome Exploration Tool (MaGnET). MaGnET consists of a light-weight Java program for effective visualisation linked to a MySQL database for data storage. In order to maximise accessibility, the program is publicly available over the World Wide Web (http://www.malariagenomeexplorer.org/). MaGnET incorporates a Genome Viewer for visualising the location of genomic features, a Protein-Protein Interaction Viewer for visualising networks of experimentally determined interactions and an Expression Data Viewer for displaying mRNA and protein expression data. Complex database queries can easily be constructed in the Data Analysis Viewer. An advantage over most other tools is that all sections are fully integrated, allowing users to carry selected groups of genes across different datasets. Furthermore, MaGnET provides useful advanced visualisation features, including mapping of expression data onto genomic location or protein-protein interaction network. The inclusion of available third-party Java software has expanded the visualisation capability of MaGnET; for example, the Jmol viewer has been incorporated for viewing 3-D protein structures. An effort has been made to only include data in MaGnET that is at least of reasonable quality. The MaGnET database collates experimental data from various public Plasmodium resources (e.g. PlasmoDB) and from published functional genomic studies, such as DNA microarrays. In addition, through careful filtering and labelling we have been able to include some predicted annotation that has not been experimentally confirmed, such as Gene Ontology and InterPro functional assignments and modelled protein structures. The application of MaGnET to malaria biology is demonstrated through a series of small studies. Initial examples show how MaGnET can be used to effectively demonstrate results from previously published analyses. This is followed up by using MaGnET to make a set of predictions about the possible functions of selected uncharacterised genes and suggesting follow-up experiments.
Download or read book Malaria Drugs Disease and Post genomic Biology written by David Sullivan and published by Springer Science & Business Media. This book was released on 2006-01-09 with total page 447 pages. Available in PDF, EPUB and Kindle. Book excerpt: Despite rapid increases in knowledge, malaria continues to kill more than a million people each year and causes symptomatic disease in a further 300 million individuals. This volume brings some of the world's best investigators to describe recent advances in both the scientific and clinical aspects of malaria, and bridges between the two.
Download or read book Genome Engineering and Functional Gene Regulation Tools for the Study of Malaria Parasites written by Diana Alejandra Falla Castillo and published by . This book was released on 2018 with total page 201 pages. Available in PDF, EPUB and Kindle. Book excerpt: Plasmodium falciparum is the causative agent of the most severe form of human malaria, a mosquito-borne disease that remains a major global health problem. The efforts to create new antimalarial drugs and effective vaccines have been significantly hindered by the lack of robust tools for performing functional genetics in P. falciparum. The identification and characterization of essential functions for parasite survival are fundamental steps towards the creation of effective antimalarial therapies. In this work, we developed an integrated set of gene editing and functional gene regulation tools that enable the study of essential and non-essential genes in blood stage parasites. We first created a robust and versatile conditional expression system that uses a fusion of endogenous translational regulatory elements and synthetic RNA-protein modules to regulate gene expression in the parasite. Using this system, we achieved tight regulation of expression of reporter and essential antimalarial genes. Next, we created an integrated strategy that utilizes our conditional system together with a CRISPR-Cas9 gene editing system to identify and characterize the function of an essential RNA-Binding protein (RBP). We first determined the essentiality of our target protein using a two-step approach, in which a merodiploid line conditionally expresses an ectopic copy of the RBP and the native gene is disrupted using CRISPR technologies. This approach was next streamlined into a single-step methodology to genetically modify native loci to regulate expression from their promoters. We performed biochemical and biological characterization of this essential protein, and established the role of this RBP in cell cycle progression and parasite schizogony. Finally, to expand the repertoire of P.falciparum target loci, we implemented the editing activity of CRISPR-Cpfl, and showed high efficiency in the disruption of non-essential genes and genes located in AT-rich regions. We also integrated the Cpfl editing activity with our conditional system to achieve conditional regulation of native loci. This work combines genome-engineering technologies and regulatory systems designed to provide a robust platform for the identification and characterization of essential functions in human malarial parasites.
Download or read book Parasite Genomics Protocols written by Sara E. Melville and published by Springer Science & Business Media. This book was released on 2008-02-02 with total page 454 pages. Available in PDF, EPUB and Kindle. Book excerpt: Parasitic diseases remain a major health problem throughout the world, for both humans and animals. For many of us, our technologically advanced lifestyle has decreased the prevalence and transmission of parasitic diseases, but for the majority of the world’s population, they are ever present in homes, domestic animals, food, or the environment. The study of parasites and parasitic disease has a long and distinguished history. In some cases, it has been driven by the great importance of the presence of the parasite to the community, for example, those that affect our livestock. In other cases, it is clear that applied research has suffered for lack of funding because the parasite affects people with few resources, such as the rural poor in resource-poor countries. These instances include the so-called “neglected diseases,” as defined by the World Health Organization (WHO). Parasites have complicated life cycles, and a thorough understanding of the unique characteristics of a particular parasite species is vital in attempts to avoid, prevent, or cure infection or to alleviate symptoms. Of course, the biological characteristics that each parasite has developed to aid survival and transmission, to avoid destruction by the immune system, and to adapt to a changing environment are of lasting fascination to basic biologists as well. The elegance of these biological systems has ensured that the study of protozoan and metazoan parasites also remains an active field of research in countries where the diseases are not a threat to the population.
Download or read book Genomics and Transcriptomics Approaches to Understanding Drug Resistance Mechanisms in the Malaria Parasite Plasmodium Falciparum written by Justin Allan Gibbons and published by . This book was released on 2019 with total page 184 pages. Available in PDF, EPUB and Kindle. Book excerpt: The malaria parasite Plasmodium falciparum is responsible for about 500,000 deaths a year and is evolving resistance to the front-line treatment of artemisinin-based combination therapy. Resistance is currently confined to South East Asia, however millions of lives will be at risk if resistance spreads to Africa. Understanding the mechanism of resistance to artemisinins would aid containment strategies to prevent the spread of artemisinin resistance. There is also an urgent need to accelerate drug discovery since drug resistance has already been documented to all existing antimalarials. Here, I report on our efforts to understand the function of the gene k13, the gene with the strongest association with artemisinin resistance, and the potential genetic mechanisms associated with resistance to atovaquone, another widely used antimalarial. To precisely study the transcriptome characteristics of an isogenic k13 dysregulation mutant and wild type strain, I developed a new computational algorithm called Dephasing Identifier (DI) that is capable of identifying the genes dysregulated in cell cycle shifts. DI is designed to solve the problem of pinpointing important patterns in complex genomics data with temporal sequences that cannot be resolved by standard pair-wise comparison methods, by using an innovative method that leverages external reference data for systematic comparisons. In the k13 study, I demonstrated that the algorithm identifies co- regulated gene sets that have consistent annotated functions. The DI algorithm successfully identified aberrantly early DNA replication as the driving process of transcriptome changes in the mutant. To understand genome-wide changes that occurred in a set of atovaquone resistance stains, I analyzed whole genome sequencing data previously generated for a P. falciparum strain that underwent in vitro atovaquone selection to create atovaquone resistant strains. I systematically analyzed the genomes of these strains to search for significant genetic changes associated with atovaquone resistance; and used stringent criteria to identify genes involved in regulating transcription and protein modifications as acquiring non- synonymous mutations. Additionally, copy number variations in plasmepsin genes, a family known to be involved in resistance, were found in the resistant strains. In summary, genomics and transcriptomics technologies can be used to rapidly identify resistance mechanisms allowing for faster adjustment of current containment strategies. Future research on the critical targets identified in this study can aid new drug discovery efforts and novel control strategies.
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 Malaria Genome Sequencing Project written by and published by . This book was released on 2000 with total page 25 pages. Available in PDF, EPUB and Kindle. Book excerpt: The objectives of this 5-year Cooperative Agreement between TIGR and the Malaria Program, NMRC, were to: Specific Aim 1, sequence 3.5 Mb of P. falciparum genomic DNA; Specific Aim 2, annotate the sequence; Specific Aim 3, release the information to the scientific community. To date, we have published the first complete sequence of a malarial chromosome (chromosome 2 4 ), completed the random phase sequencing of 3 other large chromosomes totaling 7.2 Mb, and have initiated functional genomics studies using glass slide micorarrays to characterize the expression of chromosome 2, 3, and 14 genes throughout the erythrocytic cycle. We have also collaborated in the construction of a two-enzyme optical restriction map of the entire P. falciparum genome 7 , and are continuing to further develop the GlimmerM gene finding software developed in year 1. In addition, we have begun small scale sequencing of the rodent malaria P. yoelii and are collaborating in the sequencing of part of a P. vi vax chromosome. Discussions with the Malaria Program, NMRC aimed at development of a program to use genomics and functional genomics to accelerate vaccine research are in progress.
Download or read book Plasmodium Genome written by Nature Publishing Group and published by . This book was released on 2003 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Recombination and Genome Evolution in Plasmodium Falciparum written by Martine Marianne Zilversmit and published by . This book was released on 2007 with total page 232 pages. Available in PDF, EPUB and Kindle. Book excerpt: The first chapter is a broad overview of the micro- and macroevolutionary history of human malaria parasites, with a particular emphasis on its application to medical genetics, and presents the context for all subsequent chapters.
