Objective
The mitochondrial pathway of apoptosis is the major form of programmed cell death in vertebrates. In this pathway, pro-apoptotic members of the Bcl-2 protein family cause mitochondrial outer membrane permeabilisation (MOMP) leading to the release of mitochondrial intermembrane space proteins that activate caspase proteases and apoptosis. Regulation of MOMP has been intensively investigated because it represents a crucial, and potentially targetable, process that determines cell survival.
Upon initiation, MOMP has previously been shown to occur synchronously and quickly in all mitochondria in less than ten minutes. However, using a new approach that mimics cancer cells that are primed to die, I find that the duration of MOMP can take over one hour in some cells (termed here slow MOMP). Importantly, cells that undergo slow MOMP fail to display overt signs of caspase activity and survive in the short-term, strongly indicating that caspase activity and kinetics of MOMP are tightly linked. My first objectives are to understand what controls differential MOMP kinetics and define how these regulate caspase activity and cell survival.
Furthermore, I have recently found that some mitochondria can remain intact upon MOMP. This suggests that under normal or stressed conditions a minority of mitochondria can undergo MOMP without triggering apoptosis (termed here accidental MOMP). A second objective will be to investigate the occurrence of accidental MOMP and understand its impact upon caspase activity and cell viability. To meet both objectives I will use a variety of biochemical and cell biological methods including extensive and novel live-cell imaging techniques.
This project will provide new insight into how MOMP and cell survival are regulated. It is expected that results and knowledge obtained from this work will contribute towards efforts to therapeutically target MOMP in various diseases such as cancer.
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: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences clinical medicine oncology
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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.
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.
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.
FP7-PEOPLE-2012-CIG
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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.
MC-CIG - Support for training and career development of researcher (CIG)
Coordinator
G12 8QQ Glasgow
United Kingdom
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.