PlasmoGEM history

Project history

PlasmoGEM begun at the Wellcome Sanger Institute in 2008 out of the realization that more scalable experimental genetic tools were needed to achieve a better understanding of gene functions in malaria parasites.

PlasmoGEM became one pillar of the institute’s Malaria Programme. Other notable activities of the programme included the provision of Plasmodium references genomes and MalariaGEN, a whole genome sequencing-driven initiative which created a global community of researchers seeking to understand the epidemiology, evolution, and pathogenesis of human malaria by studying natural genetic variation in humans, parasites, and mosquitoes. The Malaria Programme also overcame challenges of recombinantly expressing Plasmodium proteins, and the resulting libraries of surface proteins have found many applications. More recently, the Malaria Cell Atlas and genome assemblies of dozens of Anopheles species were added to the resources generated by the programme, which was characterized by research teams that collaborated seamlessly with each other and the broader community to identify and overcome technical roadblocks for malaria research, to produce open resources of data and reagents, and to share knowledge through courses and conferences.

During the past decade, PlasmoGEM has distributed hundreds of reagents to dozens of labs worldwide. In 2018, the PlasmoGEM phenotyping work and database moved to the Laboratory for Molecular Infection Medicine Sweden, the Swedish EMBL node at Umeå University. Vector production at the Sanger Institute ceased in 2020, as the emphasis shifted to using the vectors in genetic screens to reveal gene functions.

A redesigned reagent database (“PlasmoGEM Vectors”) was expanded with data from genetic screens (“PlasmoGEM Phenotypes”). This database will soon be hosted at the Pathogens Portal provided by the Swedish Science for Life Laboratory (SciLifeLab). Reagents continue to be distributed from the Sanger Institute.

Timeline

• 2008: Efforts to develop a scalable gene KO system in P. berghei begin.
• 2013: LIM system in place and protocol to engineer long-arm vectors. Quality control in place. Scale-up and start of vector production at scale.
• 2015: PlasmoGEM database published (Schwach et al., 2015) and screening protocol for barseq screening.
• 2016: A resource of P. berghei artificial chromosomes harboring sufficiently long inserts to cover most genes with their control regions.
• 2016: Genomic library for P. chabaudi and proof of principle recombineering of effective targeting vectors for this species.
• 2017-24: Large-scale screens for essentiality, passage through the liver, gametocytogenesis and fertility.
• 2022: PlasmoGEM database recreated at Umeå University.
• 2024: “PlasmoGEM phenotypes” database released. >12,000 phenotype measurements added to PlasmoGEM database.