Project acronym EXCHANGE
Project Forensic Geneticists and the Transnational Exchange of DNA data in the EU: Engaging Science with Social Control, Citizenship and Democracy
Researcher (PI) Helena Cristina Ferreira Machado
Host Institution (HI) UNIVERSIDADE DO MINHO
Country Portugal
Call Details Consolidator Grant (CoG), SH2, ERC-2014-CoG
Summary Today we are living in the “genetic age” of criminal investigation. There is a widespread cultural belief that DNA technology has the unrivalled capacity to identify authors of crimes. In light of this ideology, EU Law (Prüm Decision, 2008) obliges all Member States to create the conditions for the reciprocal automated searching and comparison of information on DNA data for the purpose of combating cross-border crime, terrorism and illegal immigration. Forensic geneticists play a crucial role in this scenario: they develop the techno-scientific procedures that enable DNA data to be shared across national boundaries. EXCHANGE aims to understand the close links between a highly specialised field of expert knowledge – forensic genetics – and surveillance in the EU.
If the EU succeeds in this political project, about 10 million genetic profiles of identified individuals will be exchanged between agencies in all EU countries. This raises acute cultural, political and societal challenges. EXCHANGE aims to address these challenges by scrutinizing how forensic geneticists, within the context of the transnational exchange of DNA data in the EU, engage with the social values attributed to science – i.e. objectivity, truth – and the values of social control, citizenship and democracy.
The expected outputs are: 1. To provide a general picture of the Prüm framework by conducting interviews with forensic geneticists in all EU countries; 2. To develop in-depth knowledge of forensic geneticists’ activities relating to Prüm using ethnographic observation and qualitative analysis of criminal cases; 3. To study countries with different local positionings in relation to Prüm by means of a comparative study involving Portugal, Germany, the Netherlands and the UK. EXCHANGE stimulates interdisciplinary dialogue between the social sciences and the forensic genetics. This research also tackles questions that are relevant to all the actors involved in criminal justice cooperation in the EU.
Summary
Today we are living in the “genetic age” of criminal investigation. There is a widespread cultural belief that DNA technology has the unrivalled capacity to identify authors of crimes. In light of this ideology, EU Law (Prüm Decision, 2008) obliges all Member States to create the conditions for the reciprocal automated searching and comparison of information on DNA data for the purpose of combating cross-border crime, terrorism and illegal immigration. Forensic geneticists play a crucial role in this scenario: they develop the techno-scientific procedures that enable DNA data to be shared across national boundaries. EXCHANGE aims to understand the close links between a highly specialised field of expert knowledge – forensic genetics – and surveillance in the EU.
If the EU succeeds in this political project, about 10 million genetic profiles of identified individuals will be exchanged between agencies in all EU countries. This raises acute cultural, political and societal challenges. EXCHANGE aims to address these challenges by scrutinizing how forensic geneticists, within the context of the transnational exchange of DNA data in the EU, engage with the social values attributed to science – i.e. objectivity, truth – and the values of social control, citizenship and democracy.
The expected outputs are: 1. To provide a general picture of the Prüm framework by conducting interviews with forensic geneticists in all EU countries; 2. To develop in-depth knowledge of forensic geneticists’ activities relating to Prüm using ethnographic observation and qualitative analysis of criminal cases; 3. To study countries with different local positionings in relation to Prüm by means of a comparative study involving Portugal, Germany, the Netherlands and the UK. EXCHANGE stimulates interdisciplinary dialogue between the social sciences and the forensic genetics. This research also tackles questions that are relevant to all the actors involved in criminal justice cooperation in the EU.
Max ERC Funding
1 838 150 €
Duration
Start date: 2015-10-01, End date: 2021-09-30
Project acronym IL7sigNETure
Project IL-7/IL-7R signaling networks in health and malignancy
Researcher (PI) Joao Pedro Taborda Barata
Host Institution (HI) INSTITUTO DE MEDICINA MOLECULAR JOAO LOBO ANTUNES
Country Portugal
Call Details Consolidator Grant (CoG), LS4, ERC-2014-CoG
Summary Deregulation of signal transduction is a feature of tumor cells and signaling therapies are gaining importance in the growing arsenal against cancer. However, their full potential can only be achieved once we overcome the limited knowledge on how signaling networks are wired in cancer cells. Interleukin 7 (IL7) and its receptor (IL7R) are essential for normal T-cell development and function. However, they can also promote autoimmunity, chronic inflammation and cancer. We showed that patients with T-cell acute lymphoblastic leukemia (T-ALL), an aggressive hematological cancer, can display IL7R gain-of-function mutations leading to downstream signaling activation and cell transformation. Despite the biological relevance of IL7 and IL7R, the characterization of their signaling effectors remains limited. Here, we propose to move from the single molecule/pathway-centered analysis that has characterized the research on IL7/IL7R signaling, into a ‘holistic’ view of the IL7/IL7R signaling landscape. To do so, we will employ a multidisciplinary strategy, in which data from complementary high throughput analyses, informing on different levels of regulation of the IL7/IL7R signaling network, will be integrated via a systems biology approach, and complemented by cell and molecular biology experimentation and state-of-the-art in vivo models. The knowledge we will generate should have a profound impact on the understanding of the fundamental mechanisms by which IL7/IL7R signaling promotes leukemia and reveal novel targets for fine-tuned therapeutic intervention in T-ALL. Moreover, the scope of insights gained should extend beyond leukemia. Our in-depth, systems-level characterization of IL7/IL7R signaling will constitute a platform with extraordinary potential to illuminate the molecular role of the IL7/IL7R axis in other cancers (e.g. breast and lung) and pathological settings where IL7 has been implicated, such as HIV infection, multiple sclerosis and rheumatoid arthritis.
Summary
Deregulation of signal transduction is a feature of tumor cells and signaling therapies are gaining importance in the growing arsenal against cancer. However, their full potential can only be achieved once we overcome the limited knowledge on how signaling networks are wired in cancer cells. Interleukin 7 (IL7) and its receptor (IL7R) are essential for normal T-cell development and function. However, they can also promote autoimmunity, chronic inflammation and cancer. We showed that patients with T-cell acute lymphoblastic leukemia (T-ALL), an aggressive hematological cancer, can display IL7R gain-of-function mutations leading to downstream signaling activation and cell transformation. Despite the biological relevance of IL7 and IL7R, the characterization of their signaling effectors remains limited. Here, we propose to move from the single molecule/pathway-centered analysis that has characterized the research on IL7/IL7R signaling, into a ‘holistic’ view of the IL7/IL7R signaling landscape. To do so, we will employ a multidisciplinary strategy, in which data from complementary high throughput analyses, informing on different levels of regulation of the IL7/IL7R signaling network, will be integrated via a systems biology approach, and complemented by cell and molecular biology experimentation and state-of-the-art in vivo models. The knowledge we will generate should have a profound impact on the understanding of the fundamental mechanisms by which IL7/IL7R signaling promotes leukemia and reveal novel targets for fine-tuned therapeutic intervention in T-ALL. Moreover, the scope of insights gained should extend beyond leukemia. Our in-depth, systems-level characterization of IL7/IL7R signaling will constitute a platform with extraordinary potential to illuminate the molecular role of the IL7/IL7R axis in other cancers (e.g. breast and lung) and pathological settings where IL7 has been implicated, such as HIV infection, multiple sclerosis and rheumatoid arthritis.
Max ERC Funding
1 988 125 €
Duration
Start date: 2015-09-01, End date: 2021-08-31
Project acronym iPROTECTION
Project Molecular mechanisms of induced protection against sepsis by DNA damage responses
Researcher (PI) Luis Filipe Ferreira Moita
Host Institution (HI) FUNDACAO CALOUSTE GULBENKIAN
Country Portugal
Call Details Consolidator Grant (CoG), LS4, ERC-2014-CoG
Summary Severe sepsis remains a poorly understood systemic inflammatory condition with high mortality rates and limited therapeutic options outside of infection control and organ support measures. Based on our recent discovery that anthracycline drugs prevent organ failure without affecting the bacterial burden in a model of severe sepsis, we propose that strategies aimed at target organ protection have extraordinary potential for the treatment of sepsis and possibly for other inflammation-driven conditions. However, the mechanisms of organ protection and disease tolerance are either unknown or poorly characterized.
The central goal of the current proposal is to identify and characterize novel cytoprotective mechanisms, with a focus on DNA damage response dependent protection activated by anthracyclines as a window into stress-induced genetic programs conferring disease tolerance. To that end, we will carry out a combination of candidate and unbiased approaches for the in vivo identification of ATM-dependent and independent mechanisms of tissue protection. We will validate the leading candidates through adenovirus-mediated delivery of constructs for overexpression (gain-of-function) or shRNA for gene silencing (loss-of-function) to the lung, based on our recent finding that rescuing this organ is essential and perhaps sufficient in anthracycline-induced protection against severe sepsis. The candidates showing the most promise will be characterized using a combination of in vitro and in vivo genetic, biochemical, cell biological and physiological methods.
The results arising from the current proposal are likely not only to inspire the design of transformative therapies for sepsis but also to open a completely new field of opportunity to molecularly understand core surveillance mechanisms of basic cellular processes with a critical role in the homeostasis of organ function and whose activation can ultimately promote quality of life during aging and increase lifespan.
Summary
Severe sepsis remains a poorly understood systemic inflammatory condition with high mortality rates and limited therapeutic options outside of infection control and organ support measures. Based on our recent discovery that anthracycline drugs prevent organ failure without affecting the bacterial burden in a model of severe sepsis, we propose that strategies aimed at target organ protection have extraordinary potential for the treatment of sepsis and possibly for other inflammation-driven conditions. However, the mechanisms of organ protection and disease tolerance are either unknown or poorly characterized.
The central goal of the current proposal is to identify and characterize novel cytoprotective mechanisms, with a focus on DNA damage response dependent protection activated by anthracyclines as a window into stress-induced genetic programs conferring disease tolerance. To that end, we will carry out a combination of candidate and unbiased approaches for the in vivo identification of ATM-dependent and independent mechanisms of tissue protection. We will validate the leading candidates through adenovirus-mediated delivery of constructs for overexpression (gain-of-function) or shRNA for gene silencing (loss-of-function) to the lung, based on our recent finding that rescuing this organ is essential and perhaps sufficient in anthracycline-induced protection against severe sepsis. The candidates showing the most promise will be characterized using a combination of in vitro and in vivo genetic, biochemical, cell biological and physiological methods.
The results arising from the current proposal are likely not only to inspire the design of transformative therapies for sepsis but also to open a completely new field of opportunity to molecularly understand core surveillance mechanisms of basic cellular processes with a critical role in the homeostasis of organ function and whose activation can ultimately promote quality of life during aging and increase lifespan.
Max ERC Funding
1 985 375 €
Duration
Start date: 2015-10-01, End date: 2021-03-31
Project acronym MEMOIRS
Project Children of Empires and European Postmemories
Researcher (PI) Maria Margarida DE SA CALAFATE RIBEIRO
Host Institution (HI) CENTRO DE ESTUDOS SOCIAIS
Country Portugal
Call Details Consolidator Grant (CoG), SH5, ERC-2014-CoG
Summary MEMOIRS focuses on the intergenerational memories of the children and grandchildren of those involved in the decolonization processes of colonies held by France, Portugal and Belgium. Through interviews of this second and third generation, and a comparative analysis of the cultures influenced by the postmemory of the colonial wars and the end of empire, Europe's postcolonial heritage will be reinterrogated, and a new understanding of the contemporary continent will be developed. At the heart of the project is a desire to comprehend the effects of Europe's postimperial diversity through postmemories of colonial praxis.
The project is interdisciplinary, bringing together specialists from literary and cultural studies, arts, history, sociology and migration studies. MEMOIRS aims to maximize the impact of its findings through broad web, open-access publications and an itinerant artistic exhibit that captures multiple aspects of the representations of postmemory, and fosters a meaningful North-South dialogue.
Summary
MEMOIRS focuses on the intergenerational memories of the children and grandchildren of those involved in the decolonization processes of colonies held by France, Portugal and Belgium. Through interviews of this second and third generation, and a comparative analysis of the cultures influenced by the postmemory of the colonial wars and the end of empire, Europe's postcolonial heritage will be reinterrogated, and a new understanding of the contemporary continent will be developed. At the heart of the project is a desire to comprehend the effects of Europe's postimperial diversity through postmemories of colonial praxis.
The project is interdisciplinary, bringing together specialists from literary and cultural studies, arts, history, sociology and migration studies. MEMOIRS aims to maximize the impact of its findings through broad web, open-access publications and an itinerant artistic exhibit that captures multiple aspects of the representations of postmemory, and fosters a meaningful North-South dialogue.
Max ERC Funding
1 982 475 €
Duration
Start date: 2015-11-01, End date: 2021-10-31
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) UNIVERSIDADE NOVA DE LISBOA
Country Portugal
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: 2021-08-31
