Project acronym LIMBo
Project Zooming the link between diet and brain health: how phenolic metabolites modulate brain inflammation
Researcher (PI) Cláudia NUNES DOS SANTOS
Host Institution (HI) UNIVERSIDADE NOVA DE LISBOA
Call Details Starting Grant (StG), LS9, ERC-2018-STG
Summary Currently a big concern of our aging 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, prevalent e.g. in fruits, 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. I wish to address this gap by identifying candidate compounds that can support development of effective strategies to delay neurodegeneration.
Specifically, I will be analysing the potential of dietary phenolics in both prevention and treatment (i.e delay) of neuroinflammation – key process shared in neurodegenerative diseases. To break down the current indeterminate status of “cause vs effect”, my vision is to focus my research on metabolites derived from dietary phenolics that reach the brain. I will be investigating their effects in both established and unknown response pathways of microglia cells - the innate immune cells of the central nervous system, either alone or when communicating with other brain cells. Ultimately, to attain an integrated view of their effects I will establish nutrition trials in mice. LIMBo considers both pro- and anti- inflammatory processes to preliminary validate the action of any promising metabolite in prevention and/or therapeutics.
LIMBo provides valuable scientific insights for future implementation of healthy brain diets. My group is in a unique position to address LIMBo objectives due to multidisciplinary expertise in organic synthesis, metabolomics and molecular and cellular biology, together with our previous data on novel neuroactive metabolites.
LIMBo also creates far-reaching opportunities by generating knowledge that impacts our fundamental understanding on the diversity of phenolic metabolites and their specific influences in neuroinflammation and potential use as prodrugs.
Summary
Currently a big concern of our aging 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, prevalent e.g. in fruits, 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. I wish to address this gap by identifying candidate compounds that can support development of effective strategies to delay neurodegeneration.
Specifically, I will be analysing the potential of dietary phenolics in both prevention and treatment (i.e delay) of neuroinflammation – key process shared in neurodegenerative diseases. To break down the current indeterminate status of “cause vs effect”, my vision is to focus my research on metabolites derived from dietary phenolics that reach the brain. I will be investigating their effects in both established and unknown response pathways of microglia cells - the innate immune cells of the central nervous system, either alone or when communicating with other brain cells. Ultimately, to attain an integrated view of their effects I will establish nutrition trials in mice. LIMBo considers both pro- and anti- inflammatory processes to preliminary validate the action of any promising metabolite in prevention and/or therapeutics.
LIMBo provides valuable scientific insights for future implementation of healthy brain diets. My group is in a unique position to address LIMBo objectives due to multidisciplinary expertise in organic synthesis, metabolomics and molecular and cellular biology, together with our previous data on novel neuroactive metabolites.
LIMBo also creates far-reaching opportunities by generating knowledge that impacts our fundamental understanding on the diversity of phenolic metabolites and their specific influences in neuroinflammation and potential use as prodrugs.
Max ERC Funding
1 496 022 €
Duration
Start date: 2019-04-01, End date: 2024-03-31
Project acronym MIMESIS
Project Development of biomaterials through mimesis of plant defensive interfaces to fight wound infections
Researcher (PI) Cristina Maria Da Costa Silva Pereira
Host Institution (HI) INSTITUTO DE TECNOLOGIA QUIMICA E BIOLOGICA - UNIVERSIDADE NOVA DE LISBOA
Call Details Consolidator Grant (CoG), LS9, ERC-2014-CoG
Summary Fighting microbial infection of wounds, especially in immunocompromised patients, is a major challenge in the 21st century. The skin barrier is the primary defence against microbial (opportunistic) pathogens. When this barrier is breached even non-pathogenic fungi may cause devastating infections, most of which provoked by crossover fungi able to infect both plant and humans. Hence, diabetic patients (ca. 6.4% of the world population), who are prone to develop chronic non-healing wounds, constitute a major risk group. My research is driven by the vision of mimicking the functionality of plant polyesters to develop wound dressing biomaterials that combine antimicrobial and skin regeneration properties.
Land plants have evolved through more than 400 million years, developing defence polyester barriers that limit pathogen adhesion and invasion. Biopolyesters are ubiquitous in plants and are the third most abundant plant polymer. The unique chemical composition of the plant polyester and its macromolecular assembly determines its physiological roles. This lipid-based polymer shows important similarities to the epidermal skin layer; hence it is an excellent candidate for a wound-dressing material. While evidences of their skin regeneration properties exist in cosmetics formulations and in traditional medicine, extracting polyesters from plants results in the loss of both native structure and inherent barrier properties hampering progress in this area.
We have developed a biocompatible extraction method that preserves the plant polyester film forming abilities and their inherent biological properties. The ex-situ reconstituted polyester films display the native barrier properties, including potentially broad antimicrobial and anti-biofouling effect. This, combined with our established record in fungal biochemistry/genetics, places us in a unique position to push the development of plant polyester materials to be applied in wounds, in particular diabetic chronic wounds.
Summary
Fighting microbial infection of wounds, especially in immunocompromised patients, is a major challenge in the 21st century. The skin barrier is the primary defence against microbial (opportunistic) pathogens. When this barrier is breached even non-pathogenic fungi may cause devastating infections, most of which provoked by crossover fungi able to infect both plant and humans. Hence, diabetic patients (ca. 6.4% of the world population), who are prone to develop chronic non-healing wounds, constitute a major risk group. My research is driven by the vision of mimicking the functionality of plant polyesters to develop wound dressing biomaterials that combine antimicrobial and skin regeneration properties.
Land plants have evolved through more than 400 million years, developing defence polyester barriers that limit pathogen adhesion and invasion. Biopolyesters are ubiquitous in plants and are the third most abundant plant polymer. The unique chemical composition of the plant polyester and its macromolecular assembly determines its physiological roles. This lipid-based polymer shows important similarities to the epidermal skin layer; hence it is an excellent candidate for a wound-dressing material. While evidences of their skin regeneration properties exist in cosmetics formulations and in traditional medicine, extracting polyesters from plants results in the loss of both native structure and inherent barrier properties hampering progress in this area.
We have developed a biocompatible extraction method that preserves the plant polyester film forming abilities and their inherent biological properties. The ex-situ reconstituted polyester films display the native barrier properties, including potentially broad antimicrobial and anti-biofouling effect. This, combined with our established record in fungal biochemistry/genetics, places us in a unique position to push the development of plant polyester materials to be applied in wounds, in particular diabetic chronic wounds.
Max ERC Funding
1 795 968 €
Duration
Start date: 2015-09-01, End date: 2020-08-31
Project acronym SCENT
Project SCENT: Hybrid Gels for Rapid Microbial Detection
Researcher (PI) Ana Roque
Host Institution (HI) NOVA ID FCT - ASSOCIACAO PARA A INOVACAO E DESENVOLVIMENTO DA FCT
Call Details Starting Grant (StG), LS9, ERC-2014-STG
Summary Antimicrobial resistant bacteria are a global threat spreading at an alarming pace. They cause over 25,000 annual deaths in the EU, and represent an economic burden exceeding €1.5 billion a year. Current methods for microbial detection in clinical settings take about 24-36 h, but for slow-growing bacteria, as those causing tuberculosis, it can take more than a week. Early-detection and confinement of the infected individuals are the only ways to provide adequate therapy and control infection spread. Thus, tools for rapid identification of bacterial infections are greatly needed.
The analysis of microbial volatile metabolites is an area of increasing interest in diagnostics. Recent works demonstrate that fast microbial identification is possible with chemical nose sensors. These sensors usually present limited stability and selectivity, and require aggressive conditions during processing and operation. Bioinspired nose sensors employing biological olfactory receptors are an alternative. Unfortunately, their complexity and low stability are a limitation. My group recently discovered a new class of stimulus-responsive gels which tackle these key challenges. Our gels are customisable and have a low environmental footprint associated. I intend to further explore their potential to advance the field of odour detection, while providing new tools for the scientific community. I will focus specifically in fast microbial detection. To accomplish this, I propose to 1) build libraries of hybrid gels with semi-selective and selective properties, 2) generate odorant specific peptides mimicking olfactory receptors, 3) fully characterise the gels, 4) assemble artificial noses for analysis of microbial volatiles, 5) create databases with organism-specific signal signatures, 6) identify pathogenic bacteria, including those with acquired antimicrobial-resistances. This project is a timely approach which will place Europe in the forefront of infectious disease control.
Summary
Antimicrobial resistant bacteria are a global threat spreading at an alarming pace. They cause over 25,000 annual deaths in the EU, and represent an economic burden exceeding €1.5 billion a year. Current methods for microbial detection in clinical settings take about 24-36 h, but for slow-growing bacteria, as those causing tuberculosis, it can take more than a week. Early-detection and confinement of the infected individuals are the only ways to provide adequate therapy and control infection spread. Thus, tools for rapid identification of bacterial infections are greatly needed.
The analysis of microbial volatile metabolites is an area of increasing interest in diagnostics. Recent works demonstrate that fast microbial identification is possible with chemical nose sensors. These sensors usually present limited stability and selectivity, and require aggressive conditions during processing and operation. Bioinspired nose sensors employing biological olfactory receptors are an alternative. Unfortunately, their complexity and low stability are a limitation. My group recently discovered a new class of stimulus-responsive gels which tackle these key challenges. Our gels are customisable and have a low environmental footprint associated. I intend to further explore their potential to advance the field of odour detection, while providing new tools for the scientific community. I will focus specifically in fast microbial detection. To accomplish this, I propose to 1) build libraries of hybrid gels with semi-selective and selective properties, 2) generate odorant specific peptides mimicking olfactory receptors, 3) fully characterise the gels, 4) assemble artificial noses for analysis of microbial volatiles, 5) create databases with organism-specific signal signatures, 6) identify pathogenic bacteria, including those with acquired antimicrobial-resistances. This project is a timely approach which will place Europe in the forefront of infectious disease control.
Max ERC Funding
1 500 000 €
Duration
Start date: 2015-12-01, End date: 2020-11-30
