Project description
Towards novel anti-fungal drugs
Cryptococcus neoformans is a fungal pathogen that can be life-threatening for people with weakened immune systems such as those infected with HIV. The scope of the EU-funded BiCoACC project is to discover novel anti-fungal drugs against Cryptococcus neoformans. Scientists will focus on Apt1 and Cdc50, two fungal proteins critical for fungal virulence known for their role in maintaining phospholipid asymmetry and membrane homeostasis. The biochemical characterisation of these proteins will help identify inhibitors of the Apt1/Cdc50 complex from a chemical library and assess their impact on Cryptococcus neoformans survival and virulence, paving the way for novel anti-fungal agents.
Objective
Cryptococcus neoformans is an opportunist fungal pathogen lethal for patient with AIDS. Treatment options are limited and there is an urgent need for the discovery of anti-fungal drugs. The membrane proteins Apt1 and Cdc50 from C. neoformans were identified as potential drug targets since it is involved in antifungal resistance and pathogen’s virulence. Apt1 belongs to the P4-type ATPase family and together with Cdc50 proteins they are involved in the maintenance of phospholipid asymmetry in biological membranes. In this project I plan to biochemically characterize Apt1/Cdc50 from C. neoformans, to identify inhibitors and functionally impaired mutants of this complex. These in vitro findings will be translated in vivo in C. neoformans cultures. I plan to join the Laboratoire des Protéines et des Systèmes Membranaires (LPSM) at the CEA Paris-Saclay, a world-leading lab on P4-type ATPases, where I will set up protocols for the expression and purification of the Apt1/Cdc50 complex expressed in Saccharomyces cerevisiae. Furthermore, thanks to my expertise in membrane protein reconstitution in liposomes and functional analysis, I will set up an assay to monitor in vitro phospholipid transport, an expertise still lacking at the LPSM. Using purified functional Apt1/Cdc50 complex we will screen a chemical library to identify inhibitors of this complex. In parallel a structure-function study of the complex using directed mutagenesis will be conducted. Finally, in vitro findings will be translated in vivo thanks to a collaboration with Pr Kronstad (University of British Columbia), a world expert on C. neoformans pathophysiology, where C. neoformans cultures are available. This multidisciplinary project will benefit from the expertise of the host institution on P4-ATPases, my knowledge on membrane protein reconstitution in liposomes, and the experience of Pr Kronstad on in vivo study of C. neoformans. This would allow a 3-ways transfer of expertise.
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 physiology pathophysiology
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences biological sciences microbiology mycology
- medical and health sciences health sciences infectious diseases RNA viruses HIV
- natural sciences mathematics pure mathematics mathematical analysis functional analysis
You need to log in or register to use this function
We are sorry... an unexpected error occurred during execution.
You need to be authenticated. Your session might have expired.
Thank you for your feedback. You will soon receive an email to confirm the submission. If you have selected to be notified about the reporting status, you will also be contacted when the reporting status will change.
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.
-
H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
See all projects funded under this programme -
H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
See all projects funded under this programme
Topic(s)
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.
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.
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)
See all projects funded under this funding scheme
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) H2020-MSCA-IF-2019
See all projects funded under this callCoordinator
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.
75015 Paris
France
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.