Project description
Illuminating the brain to fight Alzheimer’s
Alzheimer’s disease is the most common form of dementia. It affects millions of people worldwide and is rising sharply as populations age. To understand how the brain works and what goes wrong in neurodegeneration, scientists are turning to optogenetics. This is a method that uses light to control neurons. But current tools face major hurdles. For instance, visible light scatters too much inside tissue. Also, the key protein used, Channelrhodopsin-2 (ChR2), loses activity under prolonged illumination. Supported by the Marie Skłodowska-Curie Actions programme, the ENLIGHT project aims to reveal the molecular secrets of how ChR2 responds to light. Using quantum-classical modelling, ENLIGHT will design more precise optogenetic tools and pave the way for deeper insights into brain function and Alzheimer’s disease.
Objective
Alzheimer's disease is the most common form of dementia. It affects millions of people and is expected to increase in the coming decades due to aging of the population. Optogenetics combines optics and genetics to gain insight into brain function by genetically inserting light-sensitive transmembrane proteins into neurons. Channelrhodopsin-2 (ChR2) is an ion channel protein that enables precise temporal control turning neurons on or off in response to light. In vivo optogenetic experiments have a number of complications. One such complication is related to the wavelength of the visible light needed to activate ChR2. This results in high scattering by biological tissue as well as competition with hemoglobin which absorbs at a similar wavelength. Activation by multi-photon absorption processes (i.e. simultaneous absorption of multiple photons of longer wavelength) has the potential to mitigate both effects. Another complication is that ChR2 becomes inactive after prolonged illumination. This is related to its intricate photocycle. Gaining a detailed understanding of the molecular mechanism of the complete photocycle is crucial for solving these complications. To this end, ENLIGHT will use a holistic approach that combines multiscale quantum-classical methods, molecular dynamics simulations, and statistical analysis to obtain atomistic insight into the photoactivation, kinetics, and thermodynamics of the ChR2 photocycle. The acquired fundamental understanding of ChR2 will thus enable the development of next-generation optogenetic tools that have the potential to help us better understand the brain and neurodegenerative diseases. Dr. David Carrasco de Busturia (DCB) will carry out this project supervised by Prof. Patrick Norman at KTH, and a secondment at EPFL with Prof. Ursula Röthlisberger. This project, and the training provided, will be pivotal in advancing DCB's career goal of becoming a leading, innovative, and independent researcher in theoretical chemistry.
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 physical sciences thermodynamics
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences basic medicine neurology neurodegenerative diseases dementia
- natural sciences physical sciences theoretical physics particle physics photons
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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)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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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.
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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.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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Call for proposal
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(opens in new window) HORIZON-MSCA-2024-PF-01
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100 44 Stockholm
Sweden
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