Objective
LRRK2 is a multi-domain protein, which uniquely possesses both protein kinase and GTPase catalytic activities. Autosomal dominant mutations of LRRK2 represent one of the principal genetic risk factors for Parkinson’s Disease (PD), which results in preferential loss of neuromelanin containing, dopaminergic neurons from the substantia nigra. The (patho)physiological roles of LRRK2 are currently unclear. However, it has been linked to the regulation of endolysosmal membrane trafficking through complex formation with other PD-related gene-products (Rab7L and Vps35). LRRK2 is also highly expressed in skin pigment cells (melanocytes), which specifically produce melanin within the lysosome-related organelles known as melanosomes, in a process referred to as melanogenesis. Here we propose to examine the substrates and function of LRRK2 in pigmented melanoma cells. We will generate a MNT1 cell panel expressing PD-associated mutations of LRRK2 using CRISPR/Cas9 gene editing and characterise the respective (phospho)proteomes ±LRRK2 inhibitors from total lysates and from melanosome-enriched fractions using quantitative mass spectrometry. Melanosome biogenesis itself will be compared across the panel using electron microscopic procedures established by the experienced researcher as well as other organelle associated parameters (e.g. contacts with mitochondria) and trafficking pathways linked to Vps35 and Rab7L. The aim is to establish LRRK2 substrates or cellular consequences of activity, which may be specific to melanin-containing cells and link these to PD or to the increased incidence of melanoma observed in PD patients.
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
- medical and health sciences clinical medicine oncology skin cancer melanoma
- engineering and technology medical engineering medical laboratory technology diagnostic technologies
- medical and health sciences basic medicine neurology parkinson
- natural sciences chemical sciences analytical chemistry mass spectrometry
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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.
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H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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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-EF-ST - Standard EF
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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) H2020-MSCA-IF-2014
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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.
L69 7ZX LIVERPOOL
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.