scholarly journals Single-cell transcriptomics of malaria parasites

2017 ◽  
Author(s):  
Adam J. Reid ◽  
Arthur M. Talman ◽  
Hayley M. Bennett ◽  
Ana R. Gomes ◽  
Mandy J. Sanders ◽  
...  
Keyword(s):  
Single Cell ◽  
Gene Families ◽  
Sexual Stage ◽  
Malaria Parasites ◽  
Host Parasite Interactions ◽  
Transcriptional Variation ◽  
Single Cell Rna Sequencing ◽  
Homogeneous Cell ◽  
Host Parasite ◽  
Novel Variation

AbstractSingle-cell RNA-sequencing is revolutionising our understanding of seemingly homogeneous cell populations, but has not yet been applied to single cell organisms. Here, we established a method to successfully investigate transcriptional variation across individual malaria parasites. We discover an unexpected, discontinuous program of transcription during asexual growth previously masked by bulk analyses, and uncover novel variation among sexual stage parasites in their expression of gene families important in host-parasite interactions.

scholarly journals Single-cell RNA-seq reveals hidden transcriptional variation in malaria parasites

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Adam J Reid ◽  
Arthur M Talman ◽  
Hayley M Bennett ◽  
Ana R Gomes ◽  
Mandy J Sanders ◽  
...  
Keyword(s):  
Life Cycle ◽  
Single Cell ◽  
Rna Sequencing ◽  
Immune Evasion ◽  
Gene Families ◽  
Sexual Life ◽  
Malaria Parasites ◽  
Life Cycle Stages ◽  
Transcriptional Variation ◽  
Single Cell Rna Sequencing

Single-cell RNA-sequencing is revolutionising our understanding of seemingly homogeneous cell populations but has not yet been widely applied to single-celled organisms. Transcriptional variation in unicellular malaria parasites from the Plasmodium genus is associated with critical phenotypes including red blood cell invasion and immune evasion, yet transcriptional variation at an individual parasite level has not been examined in depth. Here, we describe the adaptation of a single-cell RNA-sequencing (scRNA-seq) protocol to deconvolute transcriptional variation for more than 500 individual parasites of both rodent and human malaria comprising asexual and sexual life-cycle stages. We uncover previously hidden discrete transcriptional signatures during the pathogenic part of the life cycle, suggesting that expression over development is not as continuous as commonly thought. In transmission stages, we find novel, sex-specific roles for differential expression of contingency gene families that are usually associated with immune evasion and pathogenesis.

scholarly journals Single-cell RNA sequencing reveals a signature of sexual commitment in malaria parasites

Nature ◽  
2017 ◽  
Vol 551 (7678) ◽  
pp. 95-99 ◽  
Author(s):  
Asaf Poran ◽  
Christopher Nötzel ◽  
Omar Aly ◽  
Nuria Mencia-Trinchant ◽  
Chantal T. Harris ◽  
...  
Keyword(s):  
Single Cell ◽  
Rna Sequencing ◽  
Malaria Parasites ◽  
Single Cell Rna Sequencing

scholarly journals Understanding human gut diseases at single-cell resolution

2020 ◽  
Vol 29 (R1) ◽  
pp. R51-R58 ◽  
Author(s):  
Emilia Bigaeva ◽  
Werna T C Uniken Venema ◽  
Rinse K Weersma ◽  
Eleonora A M Festen
Keyword(s):  
Single Cell ◽  
Digestive System ◽  
Cell Types ◽  
Specific Cell ◽  
Human Gut ◽  
The Past ◽  
Distinct Cell ◽  
Transcriptional Variation ◽  
Single Cell Rna Sequencing ◽  
Inflammatory Bowel

Abstract Our understanding of gut functioning and pathophysiology has grown considerably in the past decades, and advancing technologies enable us to deepen this understanding. Single-cell RNA sequencing (scRNA-seq) has opened a new realm of cellular diversity and transcriptional variation in the human gut at a high, single-cell resolution. ScRNA-seq has pushed the science of the digestive system forward by characterizing the function of distinct cell types within complex intestinal cellular environments, by illuminating the heterogeneity within specific cell populations and by identifying novel cell types in the human gut that could contribute to a variety of intestinal diseases. In this review, we highlight recent discoveries made with scRNA-seq that significantly advance our understanding of the human gut both in health and across the spectrum of gut diseases, including inflammatory bowel disease, colorectal carcinoma and celiac disease.

scholarly journals Functional genomics of simian malaria parasites and host–parasite interactions

2019 ◽  
Vol 18 (5) ◽  
pp. 270-280 ◽  
Author(s):  
Mary R Galinski
Keyword(s):  
Functional Genomics ◽  
Malaria Parasite ◽  
Parasite Species ◽  
Plasmodium Knowlesi ◽  
New World Monkeys ◽  
Malaria Parasites ◽  
Zoonotic Infections ◽  
Simian Malaria ◽  
Host Parasite Interactions ◽  
Host Parasite

AbstractTwo simian malaria parasite species, Plasmodium knowlesi and Plasmodium cynomolgi, cause zoonotic infections in Southeast Asia, and they have therefore gained recognition among scientists and public health officials. Notwithstanding, these species and others including Plasmodium coatneyi have served for decades as sources of knowledge on the biology, genetics and evolution of Plasmodium, and the diverse ramifications and outcomes of malaria in their monkey hosts. Experimental analysis of these species can help to fill gaps in knowledge beyond what may be possible studying the human malaria parasites or rodent parasite species. The genome sequences for these simian malaria parasite species were reported during the last decade, and functional genomics research has since been pursued. Here research on the functional genomics analysis involving these species is summarized and their importance is stressed, particularly for understanding host–parasite interactions, and potentially testing novel interventions. Importantly, while Plasmodium falciparum and Plasmodium vivax can be studied in small New World monkeys, the simian malaria parasites can be studied more effectively in the larger Old World monkey macaque hosts, which are more closely related to humans. In addition to ex vivo analyses, experimental scenarios can include passage through Anopheline mosquito hosts and longitudinal infections in monkeys to study acute and chronic infections, as well as relapses, all in the context of the in vivo host environment. Such experiments provide opportunities for understanding functional genomic elements that govern host–parasite interactions, immunity and pathogenesis in-depth, addressing hypotheses not possible from in vitro cultures or cross-sectional clinical studies with humans.

scholarly journals Plasmodium Genomics and Genetics: New Insights into Malaria Pathogenesis, Drug Resistance, Epidemiology, and Evolution

2019 ◽  
Vol 32 (4) ◽  
Author(s):  
Xin-zhuan Su ◽  
Kristin D. Lane ◽  
Lu Xia ◽  
Juliana M. Sá ◽  
Thomas E. Wellems
Keyword(s):  
Antigenic Variation ◽  
First Line ◽  
Malaria Parasites ◽  
Host Parasite Interactions ◽  
Population Structures ◽  
Causative Agents ◽  
Genomic Studies ◽  
Parasite Biology ◽  
Genetics And Genomics ◽  
Host Parasite

SUMMARY Protozoan Plasmodium parasites are the causative agents of malaria, a deadly disease that continues to afflict hundreds of millions of people every year. Infections with malaria parasites can be asymptomatic, with mild or severe symptoms, or fatal, depending on many factors such as parasite virulence and host immune status. Malaria can be treated with various drugs, with artemisinin-based combination therapies (ACTs) being the first-line choice. Recent advances in genetics and genomics of malaria parasites have contributed greatly to our understanding of parasite population dynamics, transmission, drug responses, and pathogenesis. However, knowledge gaps in parasite biology and host-parasite interactions still remain. Parasites resistant to multiple antimalarial drugs have emerged, while advanced clinical trials have shown partial efficacy for one available vaccine. Here we discuss genetic and genomic studies of Plasmodium biology, host-parasite interactions, population structures, mosquito infectivity, antigenic variation, and targets for treatment and immunization. Knowledge from these studies will advance our understanding of malaria pathogenesis, epidemiology, and evolution and will support work to discover and develop new medicines and vaccines.

scholarly journals Evolution of Host Specificity by Malaria Parasites through Altered Mechanisms Controlling Genome Maintenance

mBio ◽  
2020 ◽  
Vol 11 (2) ◽  
Author(s):  
Michelle C. Siao ◽  
Janus Borner ◽  
Susan L. Perkins ◽  
Kirk W. Deitsch ◽  
Laura A. Kirkman
Keyword(s):  
Gene Family ◽  
Family Members ◽  
Gene Families ◽  
Genome Integrity ◽  
Human Populations ◽  
Protozoan Parasites ◽  
Malaria Parasites ◽  
Content Type ◽  
Ectopic Recombination ◽  
Host Parasite

ABSTRACT The protozoan parasites that cause malaria infect a wide variety of vertebrate hosts, including birds, reptiles, and mammals, and the evolutionary pressures inherent to the host-parasite relationship have profoundly shaped the genomes of both host and parasite. Here, we report that these selective pressures have resulted in unexpected alterations to one of the most basic aspects of eukaryotic biology, the maintenance of genome integrity through DNA repair. Malaria parasites that infect humans continuously generate genetic diversity within their antigen-encoding gene families through frequent ectopic recombination between gene family members, a process that is a crucial feature of the persistence of malaria globally. The continuous generation of antigen diversity ensures that different parasite isolates are antigenically distinct, thus preventing extensive cross-reactive immunity and enabling parasites to maintain stable transmission within human populations. However, the molecular basis of the recombination between gene family members is not well understood. Through computational analyses of the antigen-encoding, multicopy gene families of different Plasmodium species, we report the unexpected observation that malaria parasites that infect rodents do not display the same degree of antigen diversity as observed in Plasmodium falciparum and appear to undergo significantly less ectopic recombination. Using comparative genomics, we also identify key molecular components of the diversification process, thus shedding new light on how malaria parasites balance the maintenance of genome integrity with the requirement for continuous genetic diversification. IMPORTANCE Malaria remains one of the most prevalent and deadly infectious diseases of the developing world, causing approximately 228 million clinical cases and nearly half a million deaths annually. The disease is caused by protozoan parasites of the genus Plasmodium, and of the five species capable of infecting humans, infections with P. falciparum are the most severe. In addition to the parasites that infect people, there are hundreds of additional species that infect birds, reptiles, and other mammals, each exquisitely evolved to meet the specific challenges inherent to survival within their respective hosts. By comparing the unique strategies that each species has evolved, key insights into host-parasite interactions can be gained, including discoveries regarding the pathogenesis of human disease. Here, we describe the surprising observation that closely related parasites with different hosts have evolved remarkably different methods for repairing their genomes. This observation has important implications for the ability of parasites to maintain chronic infections and for the development of host immunity.

scholarly journals Large, rapidly evolving gene families are at the forefront of host–parasite interactions inApicomplexa

Parasitology ◽  
2014 ◽  
Vol 142 (S1) ◽  
pp. S57-S70 ◽  
Author(s):  
ADAM J REID
Keyword(s):  
Gene Expression ◽  
Malaria Parasite ◽  
Gene Expression Regulation ◽  
Protein Localization ◽  
Animal Health ◽  
Gene Families ◽  
Sequence Diversity ◽  
Genomic Context ◽  
Host Parasite Interactions ◽  
Host Parasite

SUMMARYTheApicomplexais a phylum of parasitic protozoa, which includes the malaria parasitePlasmodium, amongst other species that can devastate human and animal health. The past decade has seen the release of genome sequences for many of the most important apicomplexan species, providing an excellent basis for improving our understanding of their biology. One of the key features of each genome is a unique set of large, variant gene families. Although closely related species share the same families, even different types of malaria parasite have distinct families. In some species they tend to be found at the ends of chromosomes, which may facilitate aspects of gene expression regulation and generation of sequence diversity. In others they are scattered apparently randomly across chromosomes. For some families there is evidence they are involved in antigenic variation, immune regulation and immune evasion. For others there are no known functions. Even where function is unknown these families are most often predicted to be exposed to the host, contain much sequence diversity and evolve rapidly. Based on these properties it is clear that they are at the forefront of host–parasite interactions. In this review I compare and contrast the genomic context, gene structure, gene expression, protein localization and function of these families across different species.

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