PlasmoGEM

Parasites and Microbes

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

Malaria is a mosquito transmitted disease that still poses a major public health problem to a large portion of the world, with 216 million cases and nearly 0.5 million deaths in 2016. Malaria is caused by Plasmodium parasites that are transmitted to people through the bites of infected female Anopheles mosquitoes. Plasmodium are single cell eukaryotes with complex life cycles, and are only very distantly related to model eukaryotes such as yeast or nematode worms. As a result, almost two decades since the completion of the first Plasmodium reference genome, nearly 50% of the 5,000+ genes in the genome lack an annotated function.

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

Contribution of PlasmoGEM to the number of P. berghei mutants catalogued in the Rodent Malaria Genetic Modification Database (https://www.pberghei.eu/index.php)
Contribution of PlasmoGEM to the number of P. berghei mutants catalogued in the Rodent Malaria Genetic Modification Database (https://www.pberghei.eu/index.php)

PlasmoGEM develops new genetic tools and makes them freely available to the malaria research community. It also uses those tools to carry out large-scale genetic screens, such as a recent screen that quantified blood-stage growth rates for knockouts of over half the Plasmodium berghei genome (Bushell et al., Cell 2017).

PlasmoGEM is a collaborative project shared across the Rayner, Lee and Billker groups.

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    [excerpt] => <strong>PlasmoGEM</strong> (the <em>Plasmodium</em> Genetic Modification Project) is an interdisciplinary group at the Wellcome Sanger Institute focussed on changing the scale of malaria experimental genetics.
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                            [post_title] => Lee Group
                            [post_excerpt] => Marcus Lee&rsquo;s group is interested in the molecular basis of drug resistance in the human malaria parasite <em>Plasmodium falciparum</em>, and&nbsp;<span title="... in developing molecular genetics tools to interrogate gene function in this important pathogen.">...</span>
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                            [post_excerpt] => While at the Sanger Institute, Julian Rayner's group investigated the molecular details of human-parasite interactions during the <em>P. falciparum</em> blood&nbsp;<span title="... stages, with a particular focus on large-scale experimental approaches to understanding erythrocyte invasion.">...</span>
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    [introduction] => <b>PlasmoGEM</b> (the <i>Plasmodium</i> Genetic Modification Project) is an interdisciplinary group at the Wellcome Sanger Institute focussed on changing the scale of malaria experimental genetics.
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                            [post_content] => <p class="MsoNoSpacing" style="margin:0cm 0cm 0.0001pt; text-align:justify"><span style="font-size:10pt"><span style="line-height:150%"><span style="font-family:&quot;Arial&quot;,&quot;sans-serif&quot;">Plasmo<span style="font-family:&quot;Arial&quot;,&quot;sans-serif&quot;">GEM</span> is a non-profit, open-access malaria research resource, providing tools for the manipulation of <em><span style="font-family:&quot;Arial&quot;,&quot;sans-serif&quot;">Plasmodium</span></em> genomes, and using them to carry out large-scale research projects. These tools currently include:</span></span></span></p><p class="MsoNoSpacing" style="margin:0cm 0cm 0.0001pt; text-align:justify"></p><p class="MsoNoSpacing" style="margin:0cm 0cm 0.0001pt; text-align:justify"><em><strong><span style="font-size:10pt"><span style="line-height:150%"><span style="font-family:&quot;Arial&quot;,&quot;sans-serif&quot;">P. berghei</span></span></span></strong></em></p><p class="MsoNoSpacing" style="margin:0cm 0cm 0.0001pt; text-align:justify"><span style="font-size:10pt"><span style="line-height:150%"><span style="font-family:&quot;Arial&quot;,&quot;sans-serif&quot;">We have produced large numbers of DNA vectors for the targeted manipulation of <em>P. berghei</em><i> </i>genes. Resources available currently include: </span></span></span></p><ul><li class="MsoNoSpacing" style="margin:0cm 0cm 0.0001pt; text-align:justify"><span style="font-size:10pt"><span style="line-height:150%"><span style="font-family:&quot;Arial&quot;,&quot;sans-serif&quot;">A large-insert (6-10kb) <em>P. berghei</em> genomic library covering &gt;90% of <em>P. berghei</em> genes</span></span></span></li><li class="MsoNoSpacing" style="margin:0cm 0cm 0.0001pt; text-align:justify"><span style="font-size:10pt"><span style="line-height:150%"><span style="font-family:&quot;Arial&quot;,&quot;sans-serif&quot;">A library of artificial chromosomes covering &gt;3500 <em>P. berghei</em> genes for use in complementation or over-expression studies.</span></span></span></li><li class="MsoNoSpacing" style="margin:0cm 0cm 0.0001pt; text-align:justify"><span style="font-size:10pt"><span style="line-height:150%"><span style="font-family:&quot;Arial&quot;,&quot;sans-serif&quot;">Gene targeting vectors for the disruption of &gt;2600 <em>P. berghei</em> genes and epitope tagging of &gt;400 genes. We are currently expanding our knockout library to attempt to cover the entire genome, excluding large multi-gene families such as <i>birs. </i></span></span></span></li><li class="MsoNoSpacing" style="margin:0cm 0cm 0.0001pt; text-align:justify"><span style="font-size:10pt"><span style="line-height:150%"><span style="font-family:&quot;Arial&quot;,&quot;sans-serif&quot;">Blood-stage growth phenotypes for &gt;2,600 genes, generated using barcode sequencing after pooled transfection with our gene targeting knock out vectors</span></span></span></li></ul><p class="MsoNoSpacing" style="margin:0cm 0cm 0.0001pt; text-align:justify"><img class="wp-image-112901 aligncenter" src="/wp-content/uploads/oct2018__p.berghei.jpg" alt="" width="718" height="644" data-credit="" /></p><p class="MsoNoSpacing" style="margin:0cm 0cm 0.0001pt; text-align:justify"><span style="font-size:10pt"><span style="line-height:150%"><span style="font-family:&quot;Arial&quot;,&quot;sans-serif&quot;">All the tools as well as phenotypic data currently available can be found <u><strong><a href="https://plasmogem.sanger.ac.uk/">here</a></strong></u>.</span></span></span></p><p class="MsoNoSpacing" style="margin:0cm 0cm 0.0001pt; text-align:justify"></p><p class="MsoNoSpacing" style="margin:0cm 0cm 0.0001pt; text-align:justify"><em><strong><span style="font-size:10pt"><span style="line-height:150%"><span style="font-family:&quot;Arial&quot;,&quot;sans-serif&quot;">P. falciparum:</span></span></span></strong></em></p><p class="MsoNoSpacing" style="margin:0cm 0cm 0.0001pt; text-align:justify"><span style="font-size:10pt"><span style="line-height:150%"><span style="font-family:&quot;Arial&quot;,&quot;sans-serif&quot;">PlasmoGEM is currently generating vectors for Cas9 and gRNA expression (pDC2) as well as barcoded homologous repair (HR) templates (pCC1) for 200-300 <em>P.falciparum</em> genes. </span></span></span></p><p class="MsoNoSpacing" style="margin:0cm 0cm 0.0001pt; text-align:justify"></p><p class="MsoNoSpacing" style="margin:0cm 0cm 0.0001pt; text-align:justify"><img class="wp-image-112902 aligncenter" src="/wp-content/uploads/oct2018__p.falciparum.jpg" alt="" width="857" height="539" data-credit="" /></p><p class="MsoNoSpacing" style="margin:0cm 0cm 0.0001pt; text-align:justify"><em><strong><span style="font-size:10pt"><span style="line-height:150%"><span style="font-family:&quot;Arial&quot;,&quot;sans-serif&quot;">P. knowlesi:</span></span></span></strong></em></p><p class="MsoNoSpacing" style="margin:0cm 0cm 0.0001pt; text-align:justify"><span style="font-size:10pt"><span style="line-height:150%"><span style="font-family:&quot;Arial&quot;,&quot;sans-serif&quot;">PlasmoGEM is currently generating vectors for Cas9 and gRNA expression (pK-U6Cas9) as well as barcoded homologous repair (HR) templates by PCR for 400-500 <em>P. knowlesi</em><i> </i>genes.</span></span></span></p><p style="margin:0cm 0cm 8pt"></p><p style="margin:0cm 0cm 8pt"><img class="wp-image-112903 aligncenter" src="/wp-content/uploads/oct2018__p.knowlesi.jpg" alt="" width="677" height="187" data-credit="" /></p>
                            [post_title] => PlasmoGEM - TOOLS
                            [post_excerpt] => Plasmo <em>GEM</em> is a non-profit, open-access malaria research resource, providing tools for the manipulation of <em>Plasmodium</em> genomes, and using them <span title="... to carry out large-scale research projects.">...</span>
                            [post_status] => publish
                            [comment_status] => closed
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                            [post_name] => plasmogem-tools
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                            [pinged] => 
                            [post_modified] => 2018-10-31 14:01:31
                            [post_modified_gmt] => 2018-10-31 14:01:31
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                            [ID] => 204155
                            [post_author] => 100332
                            [post_date] => 2015-10-08 14:23:33
                            [post_date_gmt] => 2015-10-08 14:23:33
                            [post_content] => <p class="MsoNoSpacing" style="margin:0cm 0cm 0.0001pt; text-align:justify"><span style="font-size:10pt"><span style="line-height:150%"><span style="font-family:&quot;Arial&quot;,&quot;sans-serif&quot;">PlasmoGEM currently works across three <em>Plasmodium</em><i> </i>species.</span></span></span></p><p class="MsoNoSpacing" style="margin:0cm 0cm 0.0001pt; text-align:justify"></p><p class="MsoNoSpacing" style="margin:0cm 0cm 0.0001pt; text-align:justify"><span style="font-size:10pt"><span style="line-height:150%"><span style="font-family:&quot;Arial&quot;,&quot;sans-serif&quot;"><strong><em>P. berghei</em></strong><b><i> </i></b>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 <em>P. berghei</em><i> </i>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.</span></span></span></p><p class="MsoNoSpacing" style="margin:0cm 0cm 0.0001pt; text-align:justify"></p><p class="MsoNoSpacing" style="margin:0cm 0cm 0.0001pt; text-align:justify"><img class="wp-image-112899 aligncenter" src="/wp-content/uploads/oct2018__logo.jpg" alt="" width="378" height="82" data-credit="" /></p><p class="MsoNoSpacing" style="margin:0cm 0cm 0.0001pt; text-align:justify"><span style="font-size:10pt"><span style="line-height:150%"><span style="font-family:&quot;Arial&quot;,&quot;sans-serif&quot;"><strong><em>P. falciparum</em></strong><b><i> </i></b>causes the overwhelming majority of malaria mortality, and blood stages can be grown <i>in vitro </i>in human red blood cells. PlasmoGEM is developing approaches to scale up <em>P. falciparum</em><i> </i>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 <em>P.falciparum</em> 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.</span></span></span></p><p class="MsoNoSpacing" style="margin:0cm 0cm 0.0001pt; text-align:justify"></p><p class="MsoNoSpacing" style="margin:0cm 0cm 0.0001pt; text-align:justify"><span style="font-size:10pt"><span style="line-height:150%"><span style="font-family:&quot;Arial&quot;,&quot;sans-serif&quot;"><strong><em>P. knowlesi</em></strong><b><i> </i></b>is a zoonotic pathogen of humans, and is also a close relative of <em>P. vivax</em>, which causes the majority of malaria outside Africa, but which cannot currently be cultured <em>in vitro</em><i>.</i> <em>P. knowlesi</em><i> </i>has recently been adapted to growth in human red blood cells (<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3545754/">Moon et al</a>; <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4004062/">Gruring et al</a>)<b>, </b>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 <em>P.knowlesi</em><i> </i>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.</span></span></span></p>
                            [post_title] => PlasmoGEM - The Plasmodium Genetic Modification Project
                            [post_excerpt] => PlasmoGEM provides the malaria research community with a variety of resources currently focusing on <em>P.berghei</em> , <em>P falciparum</em> and <em>P.</em> <span title="... knowlesi .">...</span>
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                            [post_modified] => 2019-05-14 10:22:20
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    [research_introduction] => For detailed information on the <em>P.berghei</em> tools and phenotypic data plase go to <a href="https://plasmogem.sanger.ac.uk/">https://plasmogem.sanger.ac.uk/</a>
    [secondary_title] => Parasites and Microbes
    [slideshow] => 
    [title] => PlasmoGEM
    [twitter] => @sangerinstitute
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                    [content] => <p style="font-weight: 400;">Malaria is a mosquito transmitted disease that still poses a major public health problem to a large portion of the world, with 216 million cases and nearly 0.5 million deaths in 2016. Malaria is caused by <em>Plasmodium</em> parasites that are transmitted to people through the bites of infected female <em>Anopheles</em><em> </em>mosquitoes. <em>Plasmodium </em>are single cell eukaryotes with complex life cycles, and are only very distantly related to model eukaryotes such as yeast or nematode worms. As a result, almost two decades since the completion of the first <em>Plasmodium</em><em> </em>reference genome, nearly 50% of the 5,000+ genes in the genome lack an annotated function.</p>
<p style="font-weight: 400;"><strong style="font-weight: 600;">PlasmoGEM</strong> (the <em>Plasmodium</em> Genetic Modification Project) is an interdisciplinary group at the Wellcome Sanger Institute focussed on changing the scale of malaria experimental genetics.</p>
<figure id="attachment_1010261" aria-describedby="caption-attachment-1010261" style="width: 300px" class="wp-caption alignright"><img loading="lazy" class="size-full wp-image-1010261" src="https://www.sanger.ac.uk/wp-content/uploads/plasmogem_contribution.jpg" alt="Contribution of PlasmoGEM to the number of P. berghei mutants catalogued in the Rodent Malaria Genetic Modification Database (https://www.pberghei.eu/index.php)" width="300" height="382" /><figcaption id="caption-attachment-1010261" class="wp-caption-text">Contribution of PlasmoGEM to the number of P. berghei mutants catalogued in the Rodent Malaria Genetic Modification Database (<a href="https://www.pberghei.eu/index.php" target="_blank" rel="noopener">https://www.pberghei.eu/index.php</a>)</figcaption></figure>
<p style="font-weight: 400;">PlasmoGEM develops new genetic tools and makes them freely available to the malaria research community. It also uses those tools to carry out large-scale genetic screens, such as a recent screen that quantified blood-stage growth rates for knockouts of over half the <em>Plasmodium berghei</em><em> </em>genome (Bushell <em>et al.</em>, Cell 2017).</p>
<p style="font-weight: 400;">PlasmoGEM is a collaborative project shared across the Rayner, Lee and Billker groups.</p>
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                                    [post_content] => 
                                    [post_title] => Lee, Marcus
                                    [post_excerpt] => Marcus Lee is interested in the molecular basis of drug resistance in the human malaria parasite <em>Plasmodium falciparum</em> , and in <span title="... developing molecular genetics approaches to interrogate gene function.">...</span>
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                                    [post_content] => 
                                    [post_title] => Herd, Colin
                                    [post_excerpt] => Advanced Research Assistant in the Billker Group looking at the Molecular and Cellular Genetics of <em>Plasmodium Bergehi</em> .
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                                    [post_title] => Metcalf, Tom
                                    [post_excerpt] => 
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                                    [post_name] => metcalf-thomas
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                                    [post_title] => Billker, Oliver
                                    [post_excerpt] => Oliver developed new genetic technologies to investigate how malaria parasites reproduce in mosquitoes and get transmitted.
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                                    [post_date] => 2019-12-04 07:00:01
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                                    [post_title] => Bronner-Anar, Burcu
                                    [post_excerpt] => I coordinate and manage the activities of the Sanger Technician Commitment team since November 2019.
                                    [post_status] => publish
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                                    [post_content] => 
                                    [post_title] => Rayner, Julian
                                    [post_excerpt] => My research seeks to understand the interactions between <em>Plasmodium</em> parasites and human cells, in order to identify and prioritise new drug&nbsp;<span title="... and vaccine targets. I focus on the stage of the parasite life cycle that infects human red blood cells, as it is this stage that causes all the symptoms and pathology of malaria.">...</span>
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                                    [post_date] => 2016-03-04 05:30:01
                                    [post_date_gmt] => 2016-03-04 05:30:01
                                    [post_content] => 
                                    [post_title] => Zenonos, Zenon A
                                    [post_excerpt] => I am interested in protein and antibody engineering and in the development of new scalable technologies for targeted genome editing
                                    [post_status] => publish
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                                    [post_name] => zenonos-zenon
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                                    [post_modified] => 2016-03-04 05:30:01
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                                    [post_content] => 
                                    [post_title] => Schwach, Frank
                                    [post_excerpt] => My main project is the development of the software tools and web portal supporting PlasmoGEM - a genome-wide resource of gene <span title="... modification vectors. The software is used to automate the gene modification design process, track constructs though the wet lab pipeline and analyse deep-sequencing data for quality control purposes. In addition, I provide bioinformatics support for various projects in the lab, including transcriptomics and proteomics assays.">...</span>
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                                    [post_date] => 2016-01-12 16:02:35
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                                    [post_content] => 
                                    [post_title] => Batista Gomes, Ana Rita
                                    [post_excerpt] => I am a post-doctoral fellow in Dr Oliver Billker&rsquo;s lab investigating the <em>P. berghei</em> metabolic pathways using a high-throughput <span title="... reverse genetics approach.">...</span>
                                    [post_status] => publish
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                                    [post_modified] => 2017-10-27 15:49:02
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                                    [post_title] => Girling, Gareth
                                    [post_excerpt] => Gareth joined the Sanger Malaria Programme in 2011 and works on the development and running of the <i>Plasmodium</i> gene targeting vector&nbsp;<span title="... pipeline that forms the basis of the Plasmodium genetic modification (PlasmoGEM) project (http://plasmogem.sanger.ac.uk/).">...</span>
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                                    [post_title] => Bushell, Ellen
                                    [post_excerpt] => Working with Oliver Billker and Julian Rayner, I am the project manager for <em>Plasmo</em> GEM (http://plasmogem.sanger.ac.uk/), <span title="... a Wellcome Trust Sanger Institute based project that generates and freely distributes tools for the genetic manipulation of the Plasmodium malaria parasites.">...</span>
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                                    [post_title] => Sanderson, Theo
                                    [post_excerpt] => I work on several projects in malaria genetics, both at the bench and <em>in silico</em> , in three different parasite species. <span title="... But these projects share one goal: to use new technologies to modify malaria parasite genomes at high scale, and thereby generate insights into the large portion of the Plasmodium genome that remains uncharacterised experimentally.">...</span>
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                                    [post_title] => Bruce, Hannah
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                            [post_title] => Lee Group
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Core team

Photo of Dr Frank Schwach

Dr Frank Schwach

Senior Computational Biologist

Photo of Mr Gareth Girling

Mr Gareth Girling

Advanced Research Assistant

Photo of Burcu Bronner-Anar, MSc

Burcu Bronner-Anar, MSc

Technician Commitment Manager

Photo of Dr Julian C Rayner

Dr Julian C Rayner

Honorary Faculty (formerly Senior Group Leader at the Sanger Institute) and Director of Wellcome Genome Campus Connecting Science

Photo of Dr Marcus Lee

Dr Marcus Lee

Group Leader

Photo of Tom Metcalf

Tom Metcalf

Advanced Research Assistant

Previous team members

Photo of Dr Theo Sanderson

Dr Theo Sanderson

Postdoctoral Fellow

Photo of Dr Oliver Billker

Dr Oliver Billker

Former Senior Group Leader

Photo of Colin Herd

Colin Herd

Advanced Research Assistant

Photo of Dr Zenon A Zenonos

Dr Zenon A Zenonos

Postdoctoral Fellow

Photo of Hannah Bruce

Hannah Bruce

Advanced Research Assistant

Photo of Dr Ana Rita Batista Gomes

Dr Ana Rita Batista Gomes

Postdoctoral Fellow

Photo of Dr Ellen Bushell

Dr Ellen Bushell

Senior Staff Scientist

 

Publications

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