H2020Индивидуална стипендия2019–2021

WolAntiS · Using antisense inhibition to understand Wolbachia symbiosis and antiviral protection

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период: 2019-03-01 → 2021-02-28
Финансиране от ЕС: 183 455 €
Участници: 1
Схема: MSCA-IF-EF-ST

Линиите свързват координатора с партньорите.

Накратко на български

Бактерията Wolbachia и начинът, по който тя спира разпространението на вируси в комори и други насекоми, се анализират чрез изключване на специфични гени. Разбирането на този механизъм помага за по-доброто контролиране на болести, пренасяни от насекоми и нематоди.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

Using antisense inhibition to understand Wolbachia symbiosis and antiviral protection

Animals are almost universally associated with microbes, interacting with them in intricate ways. Wolbachia - a maternally transmitted intracellular bacterium - is the most widespread animal symbiont, infecting 50% of known insect species. This symbiont induces a range of phenotypes, including reproductive manipulations, facilitating its own spread within host populations, and antiviral protection. Wolbachia blocks the replication of viruses and in mosquitoes it can prevent virus transmission to humans. Wolbachia is therefore a WHO-recommended strategy for the control of most vector-borne viral diseases – including dengue and Zika – and has been deployed in experimental field releases. To date, however, we lack a mechanistic understanding of Wolbachia-induced antiviral protection. This is unfortunate, as it impedes wider exploitation of the Wolbachia-insect symbioses, e.g. for disease control in species that are poor Wolbachia hosts or in designing novel treatments for viral infections. This proposal aimed at addressing key technological and knowledge deficits. The first objective was to develop an antisense strategy to target the function of Wolbachia genes. Second, to determine which Wolbachia genes are involved in animal-microbe symbiosis and antiviral protection. This work is important due to the prevalence of Wolbachia in nature and its interaction with insects (eg. pests, pollinators) and pathogenic filarial nematodes causing human disease. Understanding Wolbachia-host interaction will allow us to understand insects and nematodes better, improve current efforts to control vector-borne and filarial-caused diseases.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

Wolbachia is a widespread, intracellular symbiont of arthropods and filarial nematodes, inducing reproductive distortions and antiviral protection in insects. Wolbachia is currently being deployed in disease vector control programs and is also a target in the treatment of lymphatic filariasis. Despite its prevalence, fascinating phenotypes, and applied importance, Wolbachia biology remains poorly explored, as it cannot be cultured or genetically manipulated. To date, antisense RNA and a transfection reagent that knock down Wolbachia gene expression have been deployed in cell culture, but the effect was modest and likely very transient. In order to achieve a robust and lasting antisense inhibition in Wolbachia, applicable in an in vivo system, I will utilize developments from drug delivery and gene manipulation in other members of the Rickettsiales. This will involve the use of nuclease resistant nucleic acid analogs, which can strongly inhibit transcripts for many days. This technology will be combined with attachment to different transporter molecules, known to deliver nucleic acids to other intracellular bacteria and parasites within host cells and organisms. I will then use this system to interrogate the genes putatively involved in host-microbe interactions in cell culture. I will focus on genes underlying symbiosis and those directly conferring the trait of antiviral resistance. The technology created will be widely applicable in studies of host-symbiont interactions, and in determining the mechanisms underlying the diverse phenotypes and symbioses observed. This project will thus both enable discovery science and allow better human disease prevention and treatment.

Оригинален текст от CORDIS (на английски).

Участници

THE UNIVERSITY OF LIVERPOOL · LIVERPOOLКоординаторОбединеното кралство