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 Malaria Genome Sequencing Project written by and published by . This book was released on 2004 with total page 178 pages. Available in PDF, EPUB and Kindle. Book excerpt: The objectives of this Cooperative Agreement were: 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. Two Specific Aims were added to the Cooperative Agreement: Specific Aim 4, sequencing of P. yoelii to 5X coverage; Specific Aim 5, sequencing of P. vivax to 5X coverage. In 2002 the complete genome sequence of P. falciparum was published in Nature in collaboration with the Sanger Institute and Stanford University. A comparative analysis of the genome of the rodent malaria parasite P. yoelii with that of P. Falciparum was also published. The P. vivax genome has been sequenced to lOX coverage and genome closure is underway. Preliminary P. vivax sequence data has been released to the scientific community. Proteomic analyses of several stages of the P. falciparum life cycle by colleagues at the Scripps Research Institute were also supported by this Agreement. In addition, colleagues at the Malaria Program, Naval Medical Research Center have identified 700 genes expressed in P. falciparum sporozoites and 1,200 genes expressed in P. yoelii liver stages. Bioinformatic approaches were used to identify 300 genes encoding potential liver-stage antigens. The P. falciparum, P. yoelii, and P. vivax genome sequences generated by this effort have supported malaria research worldwide.
Download or read book Malaria Genome Sequence Project written by and published by . This book was released on 1999 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: The objectives of this 5-year Cooperative Agreement between TIGR and the USAMRMC, were to: Specific Aim 1, sequence 3.5 Mb) of P. falciparum gnomonic DNA; Specific Aim 2, annotate the sequence; Specific Aim 3, release the information to the scientific community. Excellent progress was made towards achievement of these goals. The complete sequence of P. falciparum chromosome 2(1 Mb) was determined, published in Science, and released on the TIGR web site (http://www.tigr.org/tdb/mdb/pfdb/pfdb.html). This is the first malaria chromosome to be sequenced by the Malaria Genome Sequencing Consortium. Many techniques were developed that will facilitate sequencing of the AT-rich P. falciparum genome, including: modification of the sequencing chemistry; development of assembly software and gap closure methods for AT-rich DNA; development of new gene finding software, GlimmerM; construction of a chromosome 2 YAC map and P. falciparum PAC libraries; and, initiation of microarray studies to examine expression of hundreds of genes. The success of this project demonstrates that the extreme AT-richness of the DNA will not prevent sequencing of the entire genome. Malaria researchers will be able to apply this information to the study of Plasmodium biology and to development of new drugs and vaccines for against malaria.
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 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 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 Parasites written by Jane M. Carlton and published by Caister Academic Press Limited. This book was released on 2013 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: This wealth of genome sequence data has provided researchers with a powerful new tool, comparative genomics, which has revolutionised research in this area.
Download or read book Whole Genome Analysis of the Human Malaria Parasites Plasmodium Vivax and P Falciparum written by Andrew Taylor Bright and published by . This book was released on 2013 with total page 291 pages. Available in PDF, EPUB and Kindle. Book excerpt: Plasmodium vivax causes 25-40% of malaria cases worldwide, yet research on this human malaria parasite has been neglected. Nevertheless, the recent publication of the P. vivax reference genome now allows genomics and systems biology approaches to be applied to this pathogen. We show here that whole genome analysis of the parasite can be achieved directly from ex vivo-isolated parasites, without the need for in vitro propagation. Additionally, we show that in-solution hybridization capture can be used to extract P. vivax DNA from human contaminating DNA in the laboratory without the need for on-site leukocyte filtration. Utilizing a whole genome capture method, we were able to enrich P. vivax DNA from bulk genomic DNA from less than 0.5% to a median of 55% (range 20%-80%). This level of enrichment allows for efficient analysis of the samples by whole genome sequencing and does not introduce any gross biases into the data. These techniques were subsequently used to investigate the dormant hepatic stages, known as hypnozoites, in P. vivax. This unique parasite stage is an important reservoir of infection and a critical barrier to malaria eradication. At present there are no biomarkers to identify this tissue stage and estimates of the prevalence of infections due to hypnozoites are confounded by the inability to distinguish between new and relapsing infection. Here we performed whole genome sequencing of consecutive P. vivax relapse infections using material from a patient who experienced three episodes of P. vivax malaria over 33 months in a non-endemic country. Based on patient medical history and analysis of single nucleotide variants (SNV), it was determined that two of the infections were caused by reactivation of single hypnozoites. We observe that the three recurring infections were caused by meiotic siblings. This indicates that a single sexual cross in the mosquito is capable of creating multiple distinct parasite populations, thus definitively demonstrating that the result of parasite sexual replication and meiosis in the mosquito, the oocyst, is comprised of parasites descended from a single tetrad.
Download or read book Dissecting Mechanisms of Antimalarials Using CRISPR Cas9 Editing in Plasmodium Falciparum written by SooNee Tan and published by . This book was released on 2019 with total page 123 pages. Available in PDF, EPUB and Kindle. Book excerpt: Malaria, caused by Plasmodium infections, continues to be a global disease of public health importance with 300 million annual cases and about 500,000 deaths. Continual emergence of resistance to commonly used antimalarials underscores the importance of finding new drug targets and new antimalarial drugs. Previously, the Rathod lab has established systematic approaches to study targets of antimalarials and resistance mechanisms with the use of in vitro selection methods and deep sequencing of selected mutants. There are some limitations with these approaches as deep sequencing data does not reveal the stepwise mechanism of mutagenesis and mutations observed from the sequencing result might not associate with the resistance phenotype. This thesis has multiple projects aimed to expand the molecular toolbox with genome manipulation using CRISPR/Cas9 technique. It will complement the current tools that we have in performing target identification/validation as well as understanding the mechanism of mutagenesis in malaria parasites. Ciprofloxacin is an antibacterial known to target bacterial DNA Gyrase. In some instances, ciprofloxacin has been used for malaria prophylaxis but little is known about the mode-of-action of ciprofloxacin in malaria parasites. In the first project, we aim to understand the essentiality of Plasmodium falciparum DNA gyrase A subunit (PfGyrA) and its relationship with ciprofloxacin. Based on bioinformatics analyses, PfGyr A and B subunits are known to contain apicoplast-targeting signals. To test the predicted localization of this enzyme in the apicoplast and the function of this enzyme at the subcellular level, a CRISPR/Cas9 gene-editing tool was used to disrupt PfGyrA. It is known that isopentenyl pyrophosphate (IPP) rescues malaria parasites from apicoplast-targeting inhibitors and indeed successful growth of Pf[delta]GyrA required chemical rescue with IPP. PfGyrA disruption was accompanied by loss of the plastid acyl-carrier protein (ACP) immunouorescnce and the plastid genome. Drug sensitivity assays revealed that a Pf[delta]GyrA clone, supplemented with IPP was less sensitive to antibacterial compounds (doxycycline and ciprofloxacin) but not the nuclear topoisomerase inhibitor (etoposide). In addition, at high concentrations, ciprofloxacin continued to inhibit IPP-rescued Pf[delta]GyrA suggesting that this drug has an additional target in P. falciparum. We concluded that PfGyrA is an apicoplast enzyme in malaria parasite and it is essential for blood-stage parasites. In the future, untangling the two possible inhibitory functions of ciprofloxacin in malaria parasites may reveal a new and important drug target. The second project aim involves target validation of a tetrahydroquinolone compound, BMS-388891. Previous publications from the lab showed that resistance to BMS-388891 arises from a single point mutation in either the protein farnesyl transferase (PFT) alpha or beta subunit. Although results indicated that a single point mutation on the PfPFT enzyme led to BMS-3888891 resistant parasites, whole genome sequencing on those mutants have yet to be done. To test that a single mutation is sufficient for parasite acquisition of resistance to BMS-388891, gene alteration with CRISPR/Cas9 tool was utilized to introduce a point mutation (Y837N, Y837S, or Y837C) on the PFT-[Beta]-subunit. The CRISPR-modified mutant parasites have shown an increase of 10-20 fold resistance to BMS-388891. This data is the first to formally demonstrate that a single point mutation on the Pfpft-[Beta]-subunit is sufficient for parasites to confer resistance to BMS-388891 compound. There are very few validated compound to target relationships and CRISPR/Cas9 technique will be a valuable tool in the malaria field. The third project aim involves the understanding of the mechanism of mutagenesis in malaria parasites. While it is known that amplification and point mutation are the possible outcomes of resistance selection, the order of the processes is less understood. Recent work by Guler et. al. points to a novel step-wise amplification mechanism in the malarial parasite response to DSM1 selection pressure. In these selected parasites, 25-30 kb regions surrounding the Pfdhodh locus were amplified. Taking advantage of the highly amplified Pfdhodh locus, we were able to introduce Pfpft-[alpha]-subunit into this region. This sets up future studies for us to dissect the step-wise resistance mechanism in malaria parasites. Overall, the utilization of CRISPR/Cas9 tool has allowed us to efficiently perform gene knockout, gene alteration and gene translocation. These applications not only enable us to prove for the first time the importance of the PfGyrA enzyme but also to directly confirm the causality of specific point mutations in BMS-388891 resistant parasites. The addition of CRISPR/Cas9 gene-editing to our systematic approach toolbox will ultimately aid in our understanding of how mutagenesis occurs in malaria parasites and allow us to expand our knowledge in the mode-of-action of different antimalarials in P. falciparum.
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 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 Molecular Approaches to Malaria written by Irwin W. Sherman and published by Amer Society for Microbiology. This book was released on 2005 with total page 542 pages. Available in PDF, EPUB and Kindle. Book excerpt: Molecular Approaches to Malaria provides an overview of the rapid and significant developments that have occurred in malaria research, including the 2002 genome sequencing of Plasmodium falciparum and its mosquito vector, Anopheles gambiae. Provides a concise source of up–to–date research findings Appeals to a diverse audience, including malaria researchers, teachers, investigators, and public health professionals Offers contributions by recognized malaria researchers with practical experience Presents comprehensive coverage of topics including a clearly written introduction to Plasmodium molecular biology
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 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 Genomic Variation and Evolution of the Human Malaria Parasite Plasmodium Falciparum written by Hsiao-Han Chang and published by . This book was released on 2013 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Malaria is a deadly disease that causes nearly one million deaths each year. Understanding the demographic history of the malaria parasite Plasmodium falciparum and the genetic basis of its adaptations to antimalarial treatments and the human immune system is important for developing methods to control and eradicate malaria. To study the long-term demographic history and recent effective size of the population in order to identify genes under selection more efficiently and predict the effectiveness of selection, in Chapter 2 we sequenced the complete genomes of 25 cultured P. falciparum isolates from Senegal. In addition, in Chapter 3 we estimated temporal allele frequencies in 24 loci among 528 strains from the same population across six years. Based on genetic diversity of the genome sequences, we estimate the long-term effective population size to be approximately 100,000, and a major population expansion of the parasite population approximately 20,000-40,000 years ago. Based on temporal changes in allele frequencies, however, the recent effective size is estimated to be less than 100 from 2007-2011. The discrepancy may reflect recent aggressive efforts to control malaria in Senegal or migration between populations.
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 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.
