Gene regulation of avian malaria during its life-cycle in the vector

Abstract

Malaria parasites belong to the genus Plasmodium, which infects a diverse range of host. Plasmodium relictum is one of the most widespread species of avian malaria with its diverse host ranges, causing severe disease and high mortality in many parts of the world. Plasmodium undergoes a complex lifecycle infecting two hosts: the arthropod vector and the vertebrate host. Recent RNA-seq development has enabled studies on the hostparasite relationship at the gene expression level. The parasite undergoes crucial transitions during the sporogonic cycle in the vector. In this study, I have examined the P. relictum transcriptomes extracted from its natural vector, Culex quinquefasciatus, and birds experimentally infected with P. relictum (SGS1). Statistical and ontology approaches are used on transcriptional profiles of genes across five time points during the infection episode to identify genes that are significantly up or down regulated during the different life stages in the mosquito and therefore linked to the different development stages of the parasite. I observed a large amount of invasive genes and few multifunctional genes to be active throughout the infection cycle. Transcript annotation also revealed novel genes which were significantly differentially expressed during the infection in vector. Functional enrichment investigated using annotation status and guided by already characterized genes asserts highly stage specific pathways to be overexpressed during the infection. This study provides a comprehensive insight into the molecular mechanism of the most harmful avian malaria parasite P. relictum in its natural vector system thereby providing valuable knowledge about the genes involved in critical transitions in the lifecycle of the parasite. The knowledge gathered from this study contributes to our understanding of the critical stages in Plasmodium life cycle and could be used as an active model to further conduct specific studies on targeted genes related to immune invasion.

Popular Abstract

How does Malaria survive in Mosquitos?

Malaria is a life-threatening disease that affects a wide range of organism including humans, birds, rodents and many more. It is caused by a group of single-celled parasites, which belong to the Plasmodium genus, and is mediated by mosquitoes, also known as the vector. These parasites grow within mosquitoes, but do not severally affect the mosquitoes and are transmitted to humans, birds or other organisms. In human or birds, they cause severe mortality. In some cases of birds, they have caused total extinction of some bird species. Thus, it becomes essential to study about these parasites for suitable drug targets and disease control.

We have acquired knowledge about these parasites through experiments in controlled conditions using malaria parasite that affect humans. This however does not replicate the true behavior of these parasites in natural conditions, especially in birds. It becomes a challenging task to understand the true mechanism behind the survival of these parasites in birds due to several factors such as experimental design, cost and biologically testing. This field of study has been rapidly growing and producing discoveries with advancements in technologies. We now know about how the parasite behaves in its host, i.e. birds, humans or rodents. But we are still missing useful information about how the parasite survives the defense mechanism in its vector.

Irrespective of who the parasite affects, human or birds, it undergoes a similar process in its vector. This life cycle of the parasite in its vector is called sporogonic cycle and it involves a series of stages which are critical for the parasite to survive in the vector to be able to cause further infection. The life cycle of this parasite was poorly understood until now. In this study, I have analyzed data from a recent experiment with parasite that affect birds to understand the genes, which are active during the crucial stages of the parasite growth in the vector.

The samples were first cleaned and checked for quality and contamination. As in such experiments, a large amount of sample data could come from either mosquitoes or birds. This was filtered out to reduce the sample size and to focus on genes from the parasite only. Then the data was used to estimate the parasite gene expression and to identify possible pathways that are active during these stages in the vector. As the bird parasite data lacked a huge amount of information regarding genes, comparisons based on human malaria parasite’s genes were used to guide my analysis.

The results of my analysis identified several known genes and expected pathways to be active during these stages. Many red blood cells affecting genes, probably having a significant function in immunity were active throughout the sporogonic cycle whereas some genes having very specific functions such as zygote formation and mobility where active only during certain stages. This work provides a comprehensive report about the functional classification for a major portion of the genes from my analysis. Identifying many of the known genes and pathways also suggesting that these are not only essential but also conserved within the genus. The knowledge gathered from this study will help guide further targeted research on genes related to immunity.

Master’s Degree Project in Bioinformatics 30 credits 2018
Advisors: Olof Hellgren, Dag Ahrén and Björn Canbäck
Department of Biology, Lund University

• author: Sekar, Vaishnovi
• supervisor: Olof Hellgren
• organization: Degree Projects in Bioinformatics
• course: BINP30 20172
• year: 2018
• type: H2 - Master's Degree (Two Years)
• subject: Biology and Life Sciences
• language: English
• id: 8938045
• date added to LUP: 2018-03-26 11:43:43
• date last changed: 2018-03-26 11:43:43