Project description
Kaposi’s sarcoma maintenance and latency mechanisms
Kaposi’s sarcoma herpesvirus (KSHV) is an oncogenic virus that causes tumours in immunocompromised individuals and currently has no definitive treatment. The virus relies on the host cell’s machinery to replicate and transmit its genome during latency, but specific mechanisms and proteins involved are poorly understood. The ERC-funded KAPTION project will enhance the Xenopus laevis egg extract in vitro system to study KSHV maintenance and its latency mechanisms. It will investigate the contribution of the host’s proteome to KSHV maintenance and the molecular mechanisms behind viral genome segregation. Groundbreaking findings from parallel experiments in KSHV-infected cells will address longstanding questions about KSHV latency and support the development of targeted therapies.
Objective
Oncogenic viruses are the third most common cause of cancer in humans. Kaposi’s sarcoma herpesvirus (KSHV) is an oncogenic virus that establishes life-long latent infection and can drive tumor development in immunocompromised individuals. To date no definitive treatment against KSHV has been developed and KSHV-derived cancers are uncurable. Despite the advances in understanding KSHV biology, many key aspects are still obscure, and detailed mechanistic studies are needed for the development of rational targeted therapies. During latency, KSHV exploits the host cell’s replication and segregation machineries to faithfully copy and transmit its genome during cell division. Which cellular proteins contribute to these processes and what mechanisms enable the virus to preserve its genome over time remain poorly dissected. I will remodel the Xenopus laevis egg extract in vitro system, which has been successfully applied to study eukaryotic replication and chromosome segregation, to incorporate the key components of KSHV maintenance and generate a unique tool to dissect the mechanisms of KSHV latency in a test tube. With this innovative system in hand and strong of a previously developed powerful mass-spectrometry workflow for protein identification, my group will overcome the limitations of the current methodologies to answer two main questions. (1) What is the extent of the host’s proteome that contributes to KSHV maintenance? (2) What are the molecular mechanisms that drive faithful segregation of the viral genome? Corroborated by parallel experiments in KSHV infected cells, these ground-breaking findings will answer long-standing questions on the latency of KSHV, setting a solid base for the development of targeted therapies. Furthermore, the newly developed latency system in Xenopus egg extract will emerge as a powerful tool for solving puzzling aspects of the biology of other latently infecting viruses.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences biochemistry biomolecules proteins proteomics
- natural sciences biological sciences microbiology virology
- medical and health sciences clinical medicine oncology
- natural sciences biological sciences genetics chromosomes
- natural sciences biological sciences genetics genomes
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.1 - European Research Council (ERC)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-ERC - HORIZON ERC Grants
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Call for proposal
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(opens in new window) ERC-2023-STG
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35122 PADOVA
Italy
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