The genetic analysis of natural malaria infections has been conducted at a higher resolution than ever before, providing valuable insights that could aid in understanding and preventing transmission.
A new study published today (2 May) in Science has mapped out the critical developmental stages of the malaria parasite, Plasmodium falciparum, using single-cell RNA sequencing. This has allowed researchers to gain a more detailed understanding of this constantly evolving adversary.
This article provides detailed information about the different life stages of the parasite as it goes through the process of maturing, transitioning from an asexual state to a sexual state, which is essential for the parasite to be transmitted to mosquitoes.
The research, conducted by the Wellcome Sanger Institute and the Malaria Research and Training Center (MRTC) in Mali, as well as other collaborators, contributes to the freely available Malaria Cell Atlas1. This Atlas offers valuable information for researchers worldwide to study and create tools for tracking the disease.
The new insights provided by the Malaria Cell Atlas can also help in discovering new methods to prevent the development of the parasite.Malaria is a dangerous and often fatal disease that affects millions of people worldwide each year. It is caused by the parasite known as Plasmodium, with the deadliest and most common type being P. falciparum. This particular parasite evolves rapidly, making it challenging to develop reliable diagnostics, medications, and vaccines to combat it. As a result of the parasite’s genetic diversity, preventing transmission through new drugs or vaccines is particularly difficult. In 2022 alone, there were an estimated 249 million cases of malaria and 608,000 deaths worldwide.In Mali, approximately 80% of individuals infected with malaria are often carrying several different parasite strains. Malaria parasites can be found in either a non-sexual or sexual form within the human host. The symptoms of malaria are caused by non-sexual reproduction in humans, but in order to be transmitted, the parasites must develop into male or female reproductive cells, known as gametocytes. The process of sexual commitment and development is regulated by transcription factors, which are proteins that control gene activity.The mature sexual forms of the parasite move around in the bloodstream and are later picked up by mosquitoes. The latest study, conducted by the Wellcome Sanger Institute and the MRTC in Mali, used long-read and short-read single-cell RNA sequencing to map the different stages of sexual development in the laboratory. This technique helped the researchers monitor gene expression levels and identify the specific genes involved in each stage of the process. The team also applied this method to parasites found in blood samples from four individuals naturally infected with malaria in Mali, marking the first time that this technology has been used in this way.The use of advanced technologies has allowed for the study of real-time infection strains at a very detailed level. When comparing data from laboratory experiments with data from natural infections, researchers discovered new types of parasite cells that had not been previously observed in laboratory strains. This highlights the significance of real-world data in understanding infections. The team also compared different natural strains of P. falciparum within each donor in order to identify important genes. They found that certain genes were overexpressed in specific strains during the sexual development stages, and that these genes are involved in the parasite’s survival in mosquitoes, including one that helps to suppress mosquito immunity.The next step will be to evaluate how these genes impact transmission. Jesse Rop, co-first author from the Wellcome Sanger Institute, stated that for the first time, they have been able to map the sexual development stages of malaria parasites in both laboratory and natural strains. This has provided a deeper understanding of the similarities and differences. The research has revealed new biology present in naturally occurring strains that are not observed in laboratory strains, enhancing our knowledge of malaria development and spread. Dr. Sunil Dogga, co-first author from the Wellcome Sanger Institute The Malaria Cell Atlas, which is a valuable open-access genomic resource, has been enhanced by our research, according to Professor Abdoulaye Djimdé from the Malaria Research and Training Centre, University of Bamako, Mali, and Honorary Faculty at the Wellcome Sanger Institute. This enhanced atlas will provide scientists with a clear understanding of the genes they are studying, enabling them to collaborate more effectively in their research efforts. Working together as a scientific community is essential in the fight against malaria, and this high-resolution atlas will support our efforts to prevent, control, and treat this disease.The Institute stated that malaria has a significant global impact, affecting millions of people annually. Efforts to control and treat the disease are quickly overwhelmed by the parasite. It is crucial to understand more about the parasite’s life cycle, the involved genes, and the controlling factors for ongoing malaria research. The research emphasizes key points in the sexual development of the parasite, which could be targeted in future drug development to break the transmission cycle and minimize spread. Dr. Mara Lawniczak, senior author from the Wellcome Sanger Institute, mentioned the new focus of the Malaria Cell Atlas project on n.The use of malaria vaccines for the first time aligns with the occurrence of natural infections and a growing resistance to drugs. Single-cell RNA sequencing provides insight into how parasites use genes in a way that other methods cannot, and also helps us understand the genetic diversity of parasites, even within the same person. The Malaria Cell Atlas is a valuable resource that we hope will be increasingly beneficial in the effort to eliminate malaria.
