ORCID Profile
0000-0001-6529-794X
Current Organisation
University of Leeds
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Publisher: Elsevier BV
Date: 11-2007
Abstract: With the completion of sequencing projects for several parasite genomes, efforts are ongoing to make sense of this mass of information in terms of the gene products encoded and their interactions in the growth, development and survival of parasites. The emerging science of systems biology aims to explain the complex relationship between genotype and phenotype by using network models. One area in which this approach has been particularly successful is in the modeling of metabolism. With an accurate picture of the set of metabolic reactions encoded in a genome, it is now possible to identify enzymes or transporters that might be viable targets for new drugs. Because these predictions greatly depend on the quality and completeness of the genome annotation, there are substantial efforts in the scientific community to increase the numbers of metabolic enzymes identified. In this review, we discuss the opportunities for using metabolic reconstruction and analysis tools in parasitology research, and their applications to protozoan parasites.
Publisher: Wiley
Date: 05-09-2006
DOI: 10.1016/J.FEBSLET.2006.08.063
Abstract: RNA interference (RNAi) is an RNA degradation process that involves short, double-stranded RNAs (dsRNA) as sequence specificity factors. The natural function of the RNAi machinery is to generate endogenous short double-stranded RNAs to regulate gene expression. It has been shown that treatment of Plasmodium falciparum, the etiologic agent of malaria, with dsRNA induces degradation of the corresponding microRNA (miRNA), yet typical RNAi-associated genes have not been identifiable in the parasite genome. To clarify this discrepancy we set out to clone short RNAs from P. falciparum-infected red blood cells and from purified parasites. We did not find any short RNA that was not a rRNA or tRNA fragment. Indeed, only known human miRNAs were isolated in parasite preparations indicating that very few if any short RNAs exist in P. falciparum. This suggests a different mechanism than classical RNAi in observations of dsRNA-mediated degradation. Of the human miRNAs identified, the human miRNA mir-451 accumulates at a very high level in both infected and healthy red blood cells. Interestingly, mir-451 was not detectable in a series of immortalised cell lines representing progenitor stages of all major blood lineages, suggesting that mir-451 may play a role in the differentiation of erythroid cells.
Publisher: Springer Science and Business Media LLC
Date: 17-05-2023
DOI: 10.1038/S41586-023-06034-3
Abstract: Critical illness in COVID-19 is an extreme and clinically homogeneous disease phenotype that we have previously shown 1 to be highly efficient for discovery of genetic associations 2 . Despite the advanced stage of illness at presentation, we have shown that host genetics in patients who are critically ill with COVID-19 can identify immunomodulatory therapies with strong beneficial effects in this group 3 . Here we analyse 24,202 cases of COVID-19 with critical illness comprising a combination of microarray genotype and whole-genome sequencing data from cases of critical illness in the international GenOMICC (11,440 cases) study, combined with other studies recruiting hospitalized patients with a strong focus on severe and critical disease: ISARIC4C (676 cases) and the SCOURGE consortium (5,934 cases). To put these results in the context of existing work, we conduct a meta-analysis of the new GenOMICC genome-wide association study (GWAS) results with previously published data. We find 49 genome-wide significant associations, of which 16 have not been reported previously. To investigate the therapeutic implications of these findings, we infer the structural consequences of protein-coding variants, and combine our GWAS results with gene expression data using a monocyte transcriptome-wide association study (TWAS) model, as well as gene and protein expression using Mendelian randomization. We identify potentially druggable targets in multiple systems, including inflammatory signalling ( JAK1 ), monocyte–macrophage activation and endothelial permeability ( PDE4A ), immunometabolism ( SLC2A5 and AK5 ), and host factors required for viral entry and replication ( TMPRSS2 and RAB2A ).
Publisher: Oxford University Press (OUP)
Date: 07-2006
DOI: 10.1093/NAR/GKL196
Publisher: Public Library of Science (PLoS)
Date: 11-03-2009
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Glenn McConkey.