Objective
Bacteria use various mechanisms to combat competitors and colonize new niches. The Type VI Secretion System (T6SS), a contact-dependent protein delivery apparatus, is a widespread, recently discovered machine used by Gram-negative bacteria to target competitors. Its toxicity is mediated by secreted proteins called effectors, yet the identity of many effectors, the mechanism of secretion of different effector classes, and their toxic activities remain largely unknown. I recently uncovered a widespread class of T6SS effectors that share a domain called MIX. MIX-effectors are polymorphic proteins carrying various toxin domains, many of which with unknown activities.
Many bacterial pathogens have acquired resistance to contemporary antibiotic treatments, becoming a public health threat and necessitating the development of novel antibacterial strategies. Thus, as a relatively untapped antibacterial system, studying the T6SS and its MIX-effectors presents a double incentive: 1) previously uncharacterized antibacterial activities of MIX-effectors can illuminate novel cellular targets for antibacterial drug development; 2) the T6SS machinery can be used as a novel toxin delivery platform to combat multi-drug resistant bacterial infections, using polymorphic MIX-effectors.
In this proposal, I will focus on T6SS MIX-effectors and elucidate their activities, mechanism of secretion, and utilization as antibacterial agents, by combining microbiology, molecular biology, genetic, biochemical, and proteomic approaches. Specifically, the goal of this proposal is to utilize T6SSs and MIX-effectors to develop a novel T6SS-based, antibacterial therapeutic platform in which a nonpathogenic bacterium will be engineered to carry a T6SS that can secrete a diverse repertoire of polymorphic antibacterial MIX-effectors. This innovative platform has several advantages over current antibacterial strategies, and can be used as an adjustable tool to combat multi-drug resistant bacteria.
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.
- medical and health sciences basic medicine pharmacology and pharmacy drug discovery
- natural sciences biological sciences microbiology bacteriology
- medical and health sciences health sciences public health epidemiology epidemics prevention
- medical and health sciences basic medicine pharmacology and pharmacy pharmaceutical drugs antibiotics
- medical and health sciences basic medicine pharmacology and pharmacy drug resistance multidrug resistance
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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)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC)
MAIN PROGRAMME
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Topic(s)
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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.
Funding Scheme
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.
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.
ERC-STG - Starting Grant
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2016-STG
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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.
69978 Tel Aviv
Israel
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