Edinburgh Infectious Diseases
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Research focus: from abortions in livestock to immune traits in Scottish Blackface sheep

A collection of publication highlights from the Edinburgh Infectious Diseases network over the past month.

Evaluation of species-specific polyclonal antibodies to detect and differentiate between Neospora caninum and Toxoplasma gondii

Summary: Researchers from the Moredun Research Institute and the Royal (Dick) School of Veterinary Studies have been looking at neosporosis and toxoplasmosis which are major causes of abortion in livestock, and significant economic impacts.  Researchers have developed species-specific sera that can distinguish the difference between these two diseases - something which is currently unavailable.

Lepore T, Macrae AI, Cantón GJ, Cantile C, Martineau HM, Palarea-Albaladejo J, Cahalan S, Underwood C, Katzer F, Chianini F. J Vet Diagn Invest. 2024 Feb 29:10406387241234322. doi: 10.1177/10406387241234322. Epub ahead of print. PMID: 38420701.

Dantu Blood Group Erythrocytes Form Large Plasmodium falciparum Rosettes Less Commonly

Summary: Researchers from the Institute for Immunology and Infection Research have been examining erythrocytes expressing the Dantu blood group antigen, which express proteins protective against severe malaria. There have been recent studies that show Dantu impairs Plasmodium falciparum invasion (i.e. the parasite that causes malaria), however its effects on pathological host-parasite adhesion interactions have not been investigated previously. This includes rosetting which is the binding of two or more uninfected red blood cells to an infected red blood cell and is an important factor in the development of cerebral malaria.

Researchers found that impaired rosetting resulting from altered erythrocyte membrane receptor expression and reduced MCV might add to the protective effect of Dantu blood group against severe malaria.

Carlier MSA, Nyamu W, Makale J, Williams TN, Rowe JA, Kariuki SN. Am J Trop Med Hyg. 2024 Jan 30;110(3):436-443. doi: 10.4269/ajtmh.23-0347. PMID: 38295409; PMCID: PMC10919173.

RNA-RNA interactions between respiratory syncytial virus and miR-26 and miR-27 are associated with regulation of cell cycle and antiviral immunity

Summary: Researchers from the School of Biological Sciences have been researching microRNAs which regulate all physiological processes. However, our understanding of how microRNAs function is incomplete - particularly with regard to viral infections. Researchers adapted the biochemical method and analysis pipeline in order to idenitfy targets of microRNAs in lung cells infected with Respiratory syncytial virus.

Researchers show that RSV binds directly to miR-26 and miR-27 through seed pairing and demonstrate that these miRNAs target distinct gene networks associated with cell cycle and metabolism (miR-27) and antiviral immunity (miR-26).

Ressel S, Kumar S, Bermúdez-Barrientos JR, Gordon K, Lane J, Wu J, Abreu-Goodger C, Schwarze J, Buck AH. Nucleic Acids Res. 2024 Feb 27:gkae116. doi: 10.1093/nar/gkae116. Epub ahead of print. PMID: 38412296.

Read the paper via PubMed

Predictive phage therapy for Escherichia coli urinary tract infections: Cocktail selection for therapy based on machine learning models

Summary: Researchers from the Roslin Institute and the Royal (Dick) School of Veterinary Studies have conducted a study that supports the development of predictive bacteriophage therapy: the concept of phage cocktail selection to treat bacterial infections based on machine learning models.

In doing so, researchers trained machine learning models on thousands of measured interactions between a panel of phage and sequenced bacterial isolates and applied to Escherichia coli associated for urinary tract infections. The study demonstrates the potential of predictive ML models which integrate bacterial genomics with phage activity datasets.

Keith M, Park de la Torriente A, Chalka A, Vallejo-Trujillo A, McAteer SP, Paterson GK, Low AS, Gally DL. Proc Natl Acad Sci U S A. 2024 Mar 19;121(12):e2313574121. doi: 10.1073/pnas.2313574121. Epub 2024 Mar 13. PMID: 38478693.

The landscape of the methodology in drug repurposing using human genomic data: a systematic review

Summary: Researchers from the Centre for Global Health at the Usher Institute looking at drug repurposing which, in contrast to drug development, is less expensive and can be introduce into clinical practice quicker than drug development. In the last 10 years, there has been a large expansion of biobanks that link genomic data to electronic health record data.

The review aims to provide a thorough summary of different strategies that utilise genomic data to seek drug-respositioning opportunities.

Wang L, Lu Y, Li D, Zhou Y, Yu L, Mesa Eguiagaray I, Campbell H, Li X, Theodoratou E. Brief Bioinform. 2024 Jan 22;25(2):bbad527. doi: 10.1093/bib/bbad527. PMID: 38279645; PMCID: PMC10818097.

Mitochondrial background can explain variable costs of immune deployment

Summary: Researchers from the Institute of Ecology and Evolution have been looking into immune development showing that organismal health and survival depend on the ability to mount an effective immune response against infection. Yet immune defence may be energy-demanding, resulting in fitness costs if investment in immune function deprives other physiological processes of resources.

Researchers employ Drosophila melanogaster cybrid lines, where several mitochondrial genotypes (mitotypes) were introgressed onto a single nuclear genetic background, to explicitly test the role of mitochondrial variation on the costs of immune stimulation.

Kutzer MAM, Cornish B, Jamieson M, Zawistowska O, Monteith KM, Vale PF. J Evol Biol. 2024 Mar 8:voae027. doi: 10.1093/jeb/voae027. Epub ahead of print. PMID: 38456649.

Read the paper via PubMed

Cold dispase digestion of murine lungs improves recovery and culture of airway epithelial cells

Summary: Researchers from the Centre for Inflammation Research have been looking into airway epithelial cells (AECs) which play a key role in maintaining lung homeostasis, epithelium regeneration and the initation of pulmonary immune responses. Researchers present a workflow for efficient AECs isolation and culture by utilising long and cold dispase II digestion of murine lungs.

Their findings demonstrate that temperature and duration of murine lung enzymatic digestion have a considerable impact on AEC yield, viability, and ability to form colonies in vitro. Researchers believe this workflow will be helpful for studying lung AECs and their role in the biology of lung.

Janas PP, Chauché C, Shearer P, Perona-Wright G, McSorley HJ, Schwarze J. PLoS One. 2024 Jan 25;19(1):e0297585. doi: 10.1371/journal.pone.0297585. PMID: 38271372; PMCID: PMC10810513.

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Genetic profile of adaptive immune traits and relationships with parasite resistance and productivity in Scottish Blackface sheep

Summary: Researchers from Scotland's Rural College and Moredun Research Institute have been researching gastrointestinal parasites which cause significant production losses in grazing reminants. This can be mitigated by breeding animals resistant to disease.

Lymphocyte cytokine production and parasite-specific Immunoglobulin A (IgA) are adaptive immune traits associated with immunity to GI parasites. To explore the utility of these traits for selective breeding purposes, this study estimated the genetic parameters of the immune traits in sheep and assessed their relationship with disease and productivity traits.
Pacheco A, Conington J, Corripio-Miyar Y, Frew D, Banos G, McNeilly TN. Animal. 2024 Feb;18(2):101061. doi: 10.1016/j.animal.2023.101061. Epub 2023 Dec 20. PMID: 38232660.

Read the paper via PubMed