PlasmoGEM - The Plasmodium Genetic Modification Project

PlasmoGEM - The Plasmodium Genetic Modification Project

PlasmoGEM - The Plasmodium Genetic Modification Project

PlasmoGEM currently works across three Plasmodium species.

P. berghei can infect laboratory mice, and is an extremely useful model species because it has a high transfection efficiency, and the entire life cycle can be recapitulated in a lab setting. For P. berghei we have both tools (large-insert genomic DNA libraries, artificial chromosome libraries for complementation and over-expression, gene knockout and epitope tagging vectors) and phenotypes (relative growth rates of asexual blood stages) available at genome-scale. All materials used in our pipelines as well as the final products are freely available to the non-profit research community and can be accessed via our dedicated website. All phenotypes are released as we generate them.

PlasmoGEM

P. falciparum causes the overwhelming majority of malaria mortality, and blood stages can be grown in vitro in human red blood cells. PlasmoGEM is developing approaches to scale up P. falciparum genetics, using vectors for Cas9 and gRNA expression (pDC2) in combination with barcoded homologous repair (HR) templates (pCC1) to generate knock-outs for a subset of P.falciparum genes. This project is led by Mehdi Ghorbal in the Rayner team, and in collaboration with the Sanger Institute CGaP team. Please have a look at our tools webpage to access plasmid maps.

P. knowlesi is a zoonotic pathogen of humans, and is also a close relative of P. vivax, which causes the majority of malaria outside Africa, but which cannot currently be cultured in vitro. P. knowlesi has recently been adapted to growth in human red blood cells (Moon et al; Gruring et al), and PlasmoGEM is experimenting with scaling up genetics in the Moon strain. PlasmoGEM is generating vectors for Cas9 and gRNA expression (pK-U6Cas9) and using them in combination with barcoded homologous repair (HR) templates generated by PCR to generate knock-outs for a subset of P.knowlesi genes. This project is led by Alejandro Marin Menendez in the Rayner team, and in collaboration with the Sanger Institute CGaP team. Please have a look at our tools webpage to access plasmid maps.

Research

PlasmoGEM - TOOLS

PlasmoGEM is a non-profit, open-access malaria research resource, providing tools for the manipulation of Plasmodium genomes, and using them to carry out large-scale research projects.

People

Rayner, Julian C

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Dr Julian C Rayner
Senior Group Leader and Director of Wellcome Genome Campus Connecting Science

Groups

Marcus Lee’s group is interested in the molecular basis of drug resistance in the human malaria parasite Plasmodium falciparum, and in developing molecular genetics tools to interrogate gene function in this important pathogen.

Julian Rayner's group investigates the molecular details of human-parasite interactions during the P. falciparum blood stages, with a particular focus on large-scale experimental approaches to understanding erythrocyte invasion.

Oliver Billker's group uses experimental genetics in rodent models to study the basic biology of malaria parasites and their interactions with host and mosquito vectors

PlasmoGEM (the Plasmodium Genetic Modification Project) is an interdisciplinary group at the Wellcome Sanger Institute focussed on changing the scale of malaria experimental genetics.

The Cellular Generation and Phenotyping (CGaP) core facility provides central cell biology support to the Sanger Institute, in particular the scale-up of existing protocols to facilitate 'Science at Scale'. CGaP takes a unique approach at the institute by partnering with faculty groups in order to deliver large scale projects. We function as a contract research group for the insitute, running multiple, distinct cell biology based projects. The facility has expertise in cell derivation from primary tissue, iPSC and organoid derivation, cellular differentiation, CRISPR library screens, phenotypic assays and end point analysis (e.g. Immunocytochemistry) and functional bioassays.

If you are interested in obtaining a degree level apprenticeship in the field of Cell Biology then CGaP are offering this opportunity for 1 successful candidate in 2019. The application process will open on the 1st February via https://www.findapprenticeship.service.gov.uk/apprenticeshipsearch

Publications

  • Functional Profiling of a Plasmodium Genome Reveals an Abundance of Essential Genes.

    Bushell E, Gomes AR, Sanderson T, Anar B, Girling G et al.

    Cell 2017;170;2;260-272.e8

  • A genome-scale vector resource enables high-throughput reverse genetic screening in a malaria parasite.

    Gomes AR, Bushell E, Schwach F, Girling G, Anar B et al.

    Cell host & microbe 2015;17;3;404-413

  • PlasmoGEM, a database supporting a community resource for large-scale experimental genetics in malaria parasites.

    Schwach F, Bushell E, Gomes AR, Anar B, Girling G et al.

    Nucleic acids research 2015;43;Database issue;D1176-82

  • A scalable pipeline for highly effective genetic modification of a malaria parasite.

    Pfander C, Anar B, Schwach F, Otto TD, Brochet M et al.

    Nature methods 2011;8;12;1078-82

Related Research Programmes and Facilities