Behind the paper

Share the real story behind your paper, from conception to publication, the highs and the lows.

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Using basic research in insect biology to fight disease

Many of the world’s most serious diseases are caused by pathogens that are transmitted to people by insects. Reductions in cases and deaths of these diseases have been achieved largely by using insecticides, but resistance to these chemicals now threatens those advances. Here we underline how basic research into insect biology is informing the development of new ways to control disease via targeting insect populations.
Go to the profile of W. Robert Shaw
Aug 28, 2018
Contributor

Divide and Conquer: How malaria parasites use divergent means to modify its host cell

Human malaria parasites are able to pull off a stunning trick inside our bodies. At the point at which the major disease symptoms are observed, the parasites hide inside red blood cells (RBCs); cells that are terminally differentiated and contain no nuclei or organelles that the parasite could subvert to its own ends. In addition, during the course of circulation the spleen routinely investigates RBCs and destroys those that show signs of structural damage. The trick the parasite pulls off is the ability to survive, and indeed thrive, within a cell that for all intents and purposes appears to be overtly inhospitable. Once within the cell, the parasite also establishes multiple membrane barriers (the inner parasite membrane and the outer parasitophorous vacuole membrane (PVM)) between itself and the host cell cytoplasm, therefore rendering intraerythrocytic survival even more problematic. The parasite overcomes these biological obstacles by means of a simple barcode. This signal, reported by two independent groups in 2004, is termed the Plasmodium Export Element or PEXEL. At its core, the PEXEL is a substrate for an export-licensing enzyme with the parasite endoplasmic reticulum known as Plasmepsin V or PMV. The PEXEL is found at the N-terminus of a protein following a predicted hydrophobic region (predominantly the signal sequence). Its cleavage by PMV results in the now-matured protein being exported beyond the parasitophorous vacuole and into the host cell cytoplasm. These exported proteins dramatically modify the environment of the host erythrocyte to create a niche suitable for parasite survival. We attempted to answer a critical question in disease pathogenesis involving the very beginning of this pathway. How are PEXEL-containing proteins recognised by Plasmepsin V? Using a proteomics based approach; we identified specific ER proteins that interact with PMV. The first of these, SPC25, provided the link between PMV and the protein entry site at the ER, the Sec61 translocon. Interestingly, this translocon was supplemented with an auxiliary partner protein Sec62, which converts the co-translational translocon to a post-translational form. This addition, as we identified, creates a new requirement for a distinct subset of PEXEL proteins to be fully translated in the parasite cytoplasm before being imported into the ER for PEXEL cleavage. We also discovered that the catalytic signal peptidase, which removes signal sequences, is not involved in this process and is also not associated with PMV in any form. This paper can be found here at Nature MIcrobiology: https://doi.org/10.1038/s41564-018-0219-2 In trying to answer a single question, we ended up answering several queries that had been nagging the malaria field. It also opened up exciting new avenues for exploration. What is the molecular mechanism by which Sec62 interacts with PEXEL proteins? Does it act as a direct PEXEL detector or is there an intermediary in this process? Does the translocon that imports PEXEL proteins contain novel components that could give us new insight into post-translational protein translocation? What happens to the mature PEXEL protein post-PMV cleavage? We believe that answering these questions will provide valuable information about the mechanism by which the most deadly human parasite causes disease.
Go to the profile of Danushka Marapana
Aug 26, 2018
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A new approach to malaria vaccination

Malaria is a devastating disease that affects the most vulnerable populations in the globe. It is caused by Plasmodium parasites, of which P. falciparum is the deadliest, and is transmitted by female mosquitoes, when they bite in search of a blood meal. For decades, researchers worldwide have been trying to find an effective vaccine against that which has been called the “scourge of the developing world”. Unfortunately, we are not quite there yet and the most advanced candidate in the pipeline only affords very modest levels of protection. ​​​In the beginning of the century, renewed hopes for malaria vaccination arose from the resurgence of whole-sporozoite malaria vaccines, which had been all but forgotten in the previous decades, despite offering the strongest protective efficacy ever observed in malaria vaccination. In this work, we propose an unconventional approach to the development of a new type of whole-sporozoite malaria vaccine.
Go to the profile of Miguel Prudêncio
Aug 24, 2018
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massMap: an efficient two-stage microbial association mapping framework with advanced FDR control

The two-stage microbial association mapping framework massMap provides an efficient solution for microbiome-wide association analysis. By fully exploiting the microbial dependence structures of the taxonomic tree, massMap is much more powerful than the existing methods in mapping the association at the lowest available taxonomic rank such as species or genus. We applied massMap to the analyses of the American Gut Project data and other datasets and found that massMap has marked improvement than the competing methods by discovering more biologically meaningful taxa.
Go to the profile of Jiyuan Hu
Aug 24, 2018
Contributor

An early selection for a life-long health

In general, the enteric microbiota composition is relatively stable due to the ongoing competition of bacterial members for space and nutrients. Newly arriving bacteria hardly find an empty niche and sufficient nutrients to thrive and colonize. Shortly after birth, however, this situation is markedly different. The neonate is born sterile and newly incoming bacteria can easily find a place and nutrients to stay and colonize the neonate's intestinal mucosa. Notably, it is generally thought that this process is mainly driven by exposure to bacteria derived e.g. from the mother of the environment. But is that really true? If only the environment determines the microbiota composition couldn't that go terribly wrong? Shouldn't we expect that host factors influence the emerging microbiota ensuring a beneficial bacterial composition?
Go to the profile of Mathias Hornef
Aug 08, 2018