We aim to understand the nutrition-related mechanisms of cellular processes at the molecular level and associated to lifestyle-related chronic illnesses.
We are particularly interested in the study of polyphenol metabolism in humans and animal models by metabolomics approaches, i.e. bioaccessability, bioavailability, brain permeability and cellular metabolism, and polyphenol metabolites bioactivity towards neurodegenerative diseases, focusing on Parkinson’s disease, neurodegeneration, neuroinflammation and blood brain barrier permeability.
We perform mechanistic studies using yeast, relevant cell models of disease and animals, and state-of-art cellular and molecular approaches to unravel the molecular mechanisms of cytoprotection mediated by polyphenol-derived metabolites.
Temos particular interesse no estudo do metabolismo dos polifenóis em humanos e em modelos animais utilizando abordagens metabolómicas, ou seja, bioacessibilidade, biodisponibilidade, permeabilidade cerebral e metabolismo celular, e a bioatividade dos metabolitos dos polifenóis em modelos de doenças neurodegenerativas, com foco na doença de Parkinson, neurodegeneração, neuroinflamação e permeabilidade da barreira hematoencefálica.
Realizamos estudos mecanísticos usando modelos relevantes de doenças, como os modelos de leveduras, modelos celulares e modelos animais, e abordagens celulares e moleculares de última geração para desvendar os mecanismos moleculares da citoproteção mediada por metabolitos derivados dos polifenóis.
A big concern of our society is to efficiently delay the onset of neurodegenerative diseases, which are progressively rising in incidence. The paradigm that a diet rich in the phenolics is beneficial to brain health has reached the public. However, their mechanistic actions in brain functions remain to be seen, particularly since the nature of those acting in the brain remains overlooked. LIMBO’s project addresses this gap by identifying candidate compounds that can support development of effective strategies to delay neurodegeneration. We have been analysing the potential of dietary phenolics in both prevention and treatment of neuroinflammation. We are focused on the low molecular weight (poly)phenol metabolites (LMWPM) derived from dietary phenolics and study their brain permeability and effects in both established and unknown response pathways of microglia cells either alone or when communicating with other brain cells.
The project’s 3 main objectives are:
We listed all described LMWPM and reviewed the molecular mechanisms underlying their effects in the brain and their specific role on neuroinflammation identifying the gaps. We also gather the sparse data available for the brain bioavailability of these LMWPM including evidence of crossing blood brain barrier in silico, in vitro and in vivo. Based on this we updated our library with all described LMWPM either acquiring commercially or by synthesis.
To get a comprehensive overview of LMWPM neuroprotective effects towards neuroinflammation we screen their anti-neuroinflammatory properties to protect microglia cells from a strong inflammatory insult by monitoring the release of pro-inflammatory cytokines and neurotoxic factors. Kinetics and dose response of their protective effects using near-physiological conditions of both concentration and residence time for each metabolite was established.
The brain permeability of all LMWPM was evaluated in silico and for the 3 compounds with higher activity, its brain permeability was confirmed in vivo. Compounds were injected intravenously at post-absorption physiological levels. Brain extracts were analysed for detection of the LMWPM and their end-route metabolites by untargeted metabolomics.
We aim to use specific LMWPM to study new routes of their metabolism inside the brain and push our knowledge on the neuroactive molecular mechanisms of the novel end-route metabolites. LIMBo will provide valuable scientific insights for future implementation of healthy brain diets and the potential use of phenolic metabolites as prodrugs.
ERC-2018-Starting grant (N° 804229) PI- Cláudia N Santos
Pursuant to the provisions of article 11, paragraph 2, of Decree-Law no. 57/2016, of August 29, it becomes public that by Dean’s decree of March 16, 2022, the opening of aninternational selection competition procedure was authorized for the completion of a PhDholder job vacancy for the exercise of scientific research activities financed by internationalfunds, through the European Research Council, ERC-2018-STG 804229, under anuncertain fixed-term employment contract under the Labor Code in the Faculdade deCiências Médicas|NOVA Medical School, Universidade NOVA de Lisboa.
Application Deadline: May 12, 2022
1 — The work in the scope of the project ERC-2018-STG 804229, is intended to perform the following functions:a) Develop specific research activities under the guidance of the group leader within thescope of the ERC project;b) Report and present work in the Molecular Nutrition and Health group and eventually innational and/or international meetings;c) Sharing knowledge and expertise;d) Contribute to the production of research works for publication;e) Improving established protocols and/or developing new protocols.
2 — General requirements of the application:a) Portuguese nationals, foreigners or stateless persons, holding a PhD degree in LifeSciences;b) Holders of a scientific and professional curriculum appropriate to the project to bedeveloped.
Additional information on the notice available at this page (Portuguese and English versions).
Researchers from the Molecular Nutrition and Health group presented several of their works at the Food Bioactives & Health Conference (FBHC).
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