T-FRAME
Financiado
Real time analysis of ribosomal frameshifting and its impact on immunity and dis...
The coding region of many genes contains sequence elements that constitute roadblocks during mRNA translation. These roadblocks present problems, but also opportunities for the cell to increase the coding capacity of the genome by...
The coding region of many genes contains sequence elements that constitute roadblocks during mRNA translation. These roadblocks present problems, but also opportunities for the cell to increase the coding capacity of the genome by so-called programmed ribosome frameshifting (PRF). PRF is a universal gene expression strategy that brings plasticity to the proteome. It is widely studied in viruses and bacteria, yet poorly understood in humans.
My own mechanistic discoveries have highlighted that, regardless of various stimulatory structures and slippery nucleotides involved, PRF in bacterial and viral mRNAs follows one of the two general pathways depending on substrate. In contrast, many questions remain regarding the occurrences of PRF in humans and its regulation by recently discovered trans-acting viral and cellular factors.
In T-FRAME, I will investigate the mechanism of PRF and its role in disease using HIV infection of human-T lymphocytes as an in vivo paradigm. To study molecular details of how trans-factors modulate PRF, I will leverage cutting-edge ensemble and single-molecule techniques to monitor the ribosome as it moves along the mRNA codon per codon. In addition, I will assess mRNA interactions with PRF factors during this process. Using a PRF-RNA-interactome capture assay that we have recently developed, I will search for new trans- factors in human cells. Finally, I will study the translation of T cells and HIV-1 on a global level during infection to understand the full scope and dynamic nature of PRF in this model system.
To summarize, T-FRAME will advance our understanding of how RNA structure and trans-factors shape translation regimes in higher eukaryotes and how deviations from the standard decoding path impact infection and innate immunity. I envision harnessing these findings to develop novel tools for synthetic biology and new design principles for RNA-centric antiviral and immune therapies.
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Duración del proyecto: 80 meses
Fecha Inicio: 2020-11-25
Fecha Fin: 2027-07-31
Fecha Fin: 2027-07-31
Línea de financiación: concedida
El organismo H2020 notifico la concesión del proyecto el día 2020-11-25
Línea de financiación objetivo
El proyecto se financió a través de la siguiente ayuda:
ERC-2020-STG:
ERC STARTING GRANTS
Cerrada
hace 5 años
Presupuesto
El presupuesto total del proyecto asciende a
1M€
Líder del proyecto
HELMHOLTZZENTRUM FUR INFEKTIONSFORSCHUNG GMBH
No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico
TRL
4-5
Perfil tecnológico
TRL
4-5
315.18K€ |
Participante