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Error-prone protein synthesis in fungal pathogens Microsporidia: its scope and potential therapeutic targeting

Project description

Protein synthesis errors favour parasite over host

Microsporidia are unicellular pathogenic parasites known for their capacity to form spores. Despite the potential of Microsporidia to threaten human health and industrially valuable species such as fish and cattle, their biology has been largely unexplored. The EU-funded MicroMISTRANS project combines microbiology, proteomics and molecular biology to investigate how Microsporidia can produce different protein isoforms from their genes because of errors in protein synthesis. This phenomenon of protein diversification alters the interaction with the host, leading to immune evasion with wider implications for Microsporidia infection. The results of the project could contribute to the design of more effective drugs against Microsporidia.

Objective

Microsporidia are ubiquitous and poorly treatable eukaryotic obligate intracellular pathogens that threaten human health and industrMicrosporidia are poorly treatable eukaryotic pathogens that threaten human health and industrially valuable insects, fish, and cattle. Despite Microsporidia being recognized as emerging pathogens that require development of new drugs, many aspects of their biology remain totally unexplored due to a lack of appropriate genetic tools and because only a handful of laboratories in the world can grow and manipulate Microsporidia in infected host organisms or cell cultures. This proposal involves a promising scientist with a background in biochemistry and molecular biology and who will move to a host laboratory in Newcastle University, UK – a renowned center for excellent training of young researchers, and a leading research center in the field of pathogen evolution. The researcher will undertake a multidisciplinary investigation, combining microbiology, proteomics, and molecular biology, in order to investigate how Microsporidia diversify their proteomes through error-prone protein synthesis (mistranslation). The researcher’s training at the host laboratory – in cultivating and manipulating Microsporidia in mammalian cell lines for proteomic and toxicity studies – will synergistically complement the researcher’s expertise in molecular biology of protein synthesis. Completing the project will equip the researcher with a rare, increasingly valuable and transferable skill of Microsporidia experimental biology that will be a key asset in his transition to an independent research career. The project will deliver the first detailed insights into the ability of Microsporidia to produce myriad protein isoforms from their genes as a result of highly inaccurate translation. The outcome of this project will have general implications for understanding how eukaryotic pathogens can modulate their interactions with the host and evade host immune systems.

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Topic(s)

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Funding Scheme

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MSCA-IF-EF-ST - Standard EF

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Call for proposal

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(opens in new window) H2020-MSCA-IF-2019

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Coordinator

UNIVERSITY OF NEWCASTLE UPON TYNE
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 224 933,76
Address
KINGS GATE
NE1 7RU Newcastle Upon Tyne
United Kingdom

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Region
North East (England) Northumberland and Tyne and Wear Tyneside
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 224 933,76
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