Molecular Nutrition and Health

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.

LIMBo’s Project

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:

  • Identify LMWPM in brain and screen their capability to attenuate microglia-mediated neuroinflammation
  • Elucidate the molecular mechanisms mediating the effects of LMWPM in brain cells undergoing inflammation
  • Attain an integrated perception of dietary phenolics effects in mice models of neuroinflammation and Parkinson’s disease.

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

  • ERC-2018-Starting grant,LIMBo-Zooming the link between diet and brain health: how phenolic metabolites modulate brain inflammation. (1/4/2019-31/3/2024) (in collaboration with iBET-Instituto de Biologia Experimental e Tecnológica)
  • H2020 project, CHIC-Chicory as a multipurpose crop for dietary fibre and medicinal terpenes. (1/1/2018-30/6/2022) (in collaboration with iBET-Instituto de Biologia Experimental e Tecnológica)
  • FP7 project, BacHBerry-BACterial Hosts for production of Bioactive phenolics from bERRY fruits. (29/10/2013-31/10/2016) (in collaboration with iBET)
  • FP7 project, EUBerry: The sustainable improvement of European berry production, quality and nutritional value in a changing environment. (1/5/2011-31/10/2014) (in collaboration with iBET)
  • FCT project, Therapeutics@DIAPP_Perceiving Diabetes as an Islet Amyloid PolyPeptide oligomeropathy: disease progression and therapeutic focus. (in collaboration with iBET)
  • Inova4health project, TherDIAPP_Islet Amyloid Polypeptide oligomers as critical entities in diabetes: early diagnosis and therapeutic focus. (1/1/2018-31/12/2018) (in collaboration with iBET)
  • FCT/ANR project, CardioBDP- Mechanisms of Cardioprotection by Berries-driven Polyphenols. (1/2/2014-31/07/2017) (in collaboration with iBET)
  • Fundo EDP para a Biodiversidade 2010/2012: ”Conservation and Recovery of Threatened endemic Flora in Portugal”. (in collaboration with iBET)
  • FCT project, Polyphenols as protective agents in cellular models of alpha-synucleinopaties, in particular Parkinson’s disease, (in collaboration with ITQB)

 

 

  • Prémio Inovação - 9º Encontro Nacional de Produtores de Mirtilo, 2020 (Cláudia Santos)
  • Fulbright Research Fellowship for an internship at University of Kentucky, College of Medicine, Lexington, EUA, 2019 (Ana Filipa Raimundo)
  • Food & Nutrition Awards 2019, honourable mention for Research and Development, Project: Poli4Hiper-(Poly)phenols beneficial effects in hypertension (Claúdia N. Santos, Andreia Gomes)
  • Nuno Castelo Branco Prize of Sociedade Portuguesa de Diabetologia (Portuguese Diabetes Society) for the project ""Therapeutics4DM: Towards the elucidation of Islet Amyloid Peptide role in Diabetes Mellitus – opening new venues for therapeutic intervention"", 2016 (Regina Menezes (IBET) and Rogério Ribeiro)
  • Nutrition Awards 2012, Research and Development - 2º Honorable mention, Project: Portuguese wild blackberries, new functional foods for the brain. (Lucélia Tavares; Cláudia Santos -ITQB)

 

International selection competition procedure for the hiring of a PhD holder (Aviso n.º 8636/2022 - Notice no.8636/2022) - PhD degree in Life Sciences @Cláudia Santos Lab
Investigator

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 an
international selection competition procedure was authorized for the completion of a PhD
holder job vacancy for the exercise of scientific research activities financed by international
funds, through the European Research Council, ERC-2018-STG 804229, under an
uncertain fixed-term employment contract under the Labor Code in the Faculdade de
Ciências 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 the
scope of the ERC project;
b) Report and present work in the Molecular Nutrition and Health group and eventually in
national 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 Life
Sciences;
b) Holders of a scientific and professional curriculum appropriate to the project to be
developed.

 

Additional information on the notice available at this page (Portuguese and English versions).

 

Strong presence of NMS Research in international congress on Food and Health

Researchers from the Molecular Nutrition and Health group presented several of their works at the Food Bioactives & Health Conference (FBHC).

  • Catarina Brito, Animal Cell Technology Unit, ITQB-NOVA and iBET, Oeiras, Portugal
  • Rita Ventura, Biorganic Chemistry, ITQB-NOVA, Oeiras, Portugal
  • Teresa Pais, IGC, Oeiras, Portugal
  • Maria Alexandra Brito, Faculdade de Farmácia, Universidade de Lisboa, Portugal
  • Derek Stewart, James Hutton Institute, Invergowrie, Dundee, Scotland, UK
  • Francisco Tomas-Barberan, CEBAS-CSIC, Murcia, Spain
  • Danielle Del Rio, Parma University, Parma, Italy
  • David Berry, University of Vienna, University of Vienna, Vienna, Austria
  • Florin Despa - Department of Pharmacology and Nutritional Sciences and Department of Neurology, University of Kentucky, Lexington, USA
  • Ana Novials - Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), Barcelona, Spain
  • Giovanni Meli - European Brain Research Institute (EBRI), Roma, Italy
  • Antonino Cataneo - EBRI; Scuola Normale Superiore, Pisa, Italy
  • Ivo Martins - Instituto de Medicina Molecular (IMM), Faculty of Medicine, University of Lisbon, Portugal

Principal Investigator

Cláudia Nunes dos Santos

Team

Regina Menezes
Senior Post-doctoral Researcher
Natasa Loncarevic-Vasiljkovic
Senior Post-Doctoral Researcher
Angela Ávila
Post-Doctoral Researcher
Inês Figueira
Post-Doctoral Researcher
Paulo Bastos
Post-Doctoral Researcher
Rúben Rodrigues
Post-Doctoral Researcher
Ana Filipa Raimundo
PhD Student
Catarina Pinto
PhD Student
Daniela Marques
PhD Student
Diogo Carregosa
PhD Student
Rafael Carecho
PhD Student
Rita Ramos
PhD Student
Sofia Ferreira
PhD Student
Diogo Mendes
MSc Student
Hugo Tainha
MSc Student
Sara Mota
MSc Student