Objective
The endo-lysosomal system is critical to diverse processes, including protein homeostasis, signaling and antigen presentation. The vesicular compartment is organized as a collective unit wherein the bulk of endosomes derived from disparate origins resides in a cloud in the perinuclear region and extends outwards to include quickly moving vesicles in the periphery. At this busy intersection between the endocytic and biosynthetic pathways, lies the late endosomal compartment, responsible for protein degradation and antigen processing. In dendritic and other immune cells, this major constituent of the perinuclear cloud serves as a hub for MHC class II antigen loading. Previous work by us and others has elucidated key elements of MHC class II biology through the study of late endosomal transport to and from the cell periphery. It is clear that cell biology of endosomes is modulated by their proximity to other membrane compartments during transport, maturation, cargo selection and delivery and even during cytokinesis in cell division. However, how endosomal positioning in the perinuclear cloud and how their release for further transport is controlled remains largely unknown. The aim of this proposal is to define the molecular basis for endosomal positioning and then to interrogate the relationship between spatial regulation of the endocytic compartment and its functions with respect to i) MHC class II antigen presentation, ii) bacterial infection and iii) mitotic resolution. From a genome-wide siRNA screen for factors influencing MHC class II biology, we have identified a unique and previously uncharacterized ubiquitin ligase that resides in the ER membrane, from where it controls endosomal positioning and times their arrivals and departures as a function of its catalytic activity. On this basis, the work proposed herein is poised to resolve an entirely new molecular network in control of endosomal biology with implications for diverse biological processes.
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 microbiology bacteriology
- natural sciences biological sciences cell biology
- medical and health sciences basic medicine immunology
- medical and health sciences basic medicine physiology homeostasis
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
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.1.1. - EXCELLENT SCIENCE - European Research Council (ERC)
MAIN PROGRAMME
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.
ERC-ADG - Advanced Grant
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) ERC-2015-AdG
See all projects funded under this callHost institution
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.
2333 ZA Leiden
Netherlands
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.