Where Ideas Grow

Salomé Pinho wins ERC Synergy Grant and leads European project with seven million euros of funding

The researcher Salomé Pinho was doubly distinguished during this month of October: she was the only Portuguese to have a project in the 29 European projects awarded by the European Research Council (ERC) in this year's edition of the ERC Synergy Grants (SyG) and obtained funding of seven million of euros from the European Commission's Horizon Europe Program to lead a project that aims to predict, intervene and prevent Crohn's Disease.

The project “GlycanSwitch: Glycans as main switches of B-cell activity in autoimmunity” has won an ERC Synergy Grant worth ten million euros and represents an ambitious effort in the fight against autoimmune diseases, resulting from the unprecedented synergy between four principal investigators: Salomé Pinho, leader of the “Immunology, Cancer & GlycoMedicine” group at i3S, two scientists from the University Medical Center Leiden (LUMC), the Netherlands, and a researcher from the company Genos and the University of Zagreb, Croatia. This is only the third time that a Portuguese scientist has won this grant worth ten million euros.

Immune tolerance is responsible for keeping the immune system balanced - it attacks invading agents and does not react against its own organs, tissues, or cells. When this tolerance is lost, the immune system reacts in an uncontrolled and exaggerated way which can cause some type of autoimmune disease. But what causes this loss of tolerance in the immune system? And what are the key moments when this happens, so that it is possible to detect and avoid them before the patient has symptoms? The answer will be given by the four researchers that make up the consortium.

Autoimmune diseases are chronic, debilitating, and in some cases fatal - and as such are diseases with high medical and social costs. As most of them are incurable and those with a high rate of incidence - such as Rheumatoid Arthritis, Systemic Lupus Erythematosus, juvenile diabetes (type 1) and Inflammatory Bowel Disease “have been increasing worldwide, these diseases are considered an important problem of public health that needs urgent intervention”, emphasizes Salomé Pinho. “There is a pressing need to understand the cellular and molecular mechanisms that cause the lack of control in the inflammatory response and the loss of immuno-tolerance”.

Specifically “we want to understand why, how and when the modifications of glycans (sugars/carbohydrates) in B cells (a type of lymphocytes/immune cells that act in the inflammatory response and in the production of antibodies) act as master switches that trigger abnormal B cell activity, thereby resulting in the production of pathogenic autoantibodies associated with loss of immune tolerance and the development of autoimmunity”.

In the context of what an ERC Synergy Grant means, this project is characterized by the “existence of a true synergy between the four Principal Investigators, in which the whole is greater than the sum of the parts”, explains the researcher from i3S. “There is a unique combination of know-how in rheumatology, immunology and glycobiology which, combined with the use of advanced technology in glycoproteomics and glycomics, as well as the use of cellular prototypes and unique animal models of autoimmune disease, will enable a transformative and unravel the cause of the loss of immuno-tolerance and the development of autoimmune diseases”, she adds.

“This is a project that will complete the cycle: from the molecule to the patient; since the experimental evidence that will be generated will be validated in patients with autoimmune diseases such as rheumatoid arthritis”, guarantees Salomé Pinho. The constant sharing of scientific and human resources, experimental models and advanced technology between the four researchers and their respective institutes “will allow a true scientific synergy that will enhance the discovery. There is a real interdependence between all the participants through the execution of the project towards the same objective”.

For Salomé Pinho, winning an ERC project, not to mention an ERC Synergy Grant, “is to achieve the maximum exponent of world recognition for the excellence of the research and science that we develop. The high competitiveness that characterizes ERC projects, the scientific demand and methodological rigor that characterize the evaluations of ERC projects by the European Commission through a diverse and varied range of reviewers and world experts from all scientific areas who evaluate the projects, reveals the requirement of the process and makes this outcome highly gratifying”. More than an individual recognition, this ERC represents a “collective recognition of the merit of the excellent team that has accompanied me over the years and of the scientific excellence of the institute to which I belong, i3S”.
 
European project to predict, intervene and prevent Crohn's Disease
 
The “GlycanTrigger” project, which has received seven million euros by the European Commission's Horizon Europe Program and is led by i3S, has the objective of studying the period between the symptom-free phase and when the diagnosis of Crohn's Disease is made. It is true that this can be a period of years, but it is known that the immunological changes that occur in the intestine are enormous, so it is pertinent to understand what happens in the intestinal mucosa, which causes inflammation of the intestine, and how we can prevent it.

Salomé Pinho, which coordinates this European project, explains that in Crohn's Disease “there is evidence of the existence of a pre-clinical phase (in which there are still no symptoms) that it is characterized by immunological alterations at the level of the intestinal mucosa that precede the symptoms. This pre-clinical/asymptomatic period can last for years”. In this project, adds the researcher, “we propose a completely innovative approach to better understand the transition from health (from a normal intestinal mucosa) to chronic inflammation of the intestine. It is a transformative project whose results will be translated into a better understanding of the specific mechanisms that lead to intestinal inflammation and consequently the ability to predict and prevent the disease”.

For the first time, emphasizes Salomé Pinho, “we are going to study how changes in the intestinal mucosa (specifically in the protective layer formed by sugars/glycans that covers the entire surface of the intestine) could act as a primary event, which triggers the dysregulation of the microbiome gut, consequently leading to the activation of the gut's immune response, with the production of antibodies, which will act as an early trigger that promotes the transition from health to gut inflammation”.
Over the next six years the team also intends to study how these changes that trigger the disease can be detected in the blood and, in this way, constitute a new biomarker capable of predicting the onset of intestinal inflammation years before a diagnosis of CD. In conclusion, “we will have new disease predictive tools and new early intervention strategies to prevent intestinal inflammation and CD”.

This project, called “Glycans as Key Triggers in the Health Transition to Gut Inflammation” involves a multidisciplinary team of nine European and North American partners. As a coordinating entity, i3S will receive almost 3.5 million euros to develop assays and experimental models, ranging from cellular studies, to complex animal models and analysis of patient samples.

From the i3S, in addition to the project coordinator, Salomé Pinho, the project will have the participation of researchers Joana Gaifem, Inês Alves, Manuel Vicente, Cláudia Rodrigues and Eduarda Gomes from the group “Immunology, Cancer & GlycoMedicine”, and researchers José Carlos Machado and Fátima Carneiro, from the group “Intercellular Communication and Cancer”.

To achieve the goals of GlycanTrigger, the team will use cutting-edge technologies in different research and clinical areas, complemented with detailed analysis of samples from patients with Crohn's Disease (taken before and after the disease), for which it will also count on collaboration from the gastroenterology service of the Centro Hospitalar Universitário do Porto. The participation of a European association of patients with Inflammatory Bowel Disease will ensure the involvement of civil society and the impact of this project in improving the quality of life of patients with Crohn's Disease.

In addition to i3S, the following institutions are partners in the GlycanTrigger project: Hospital da Luz – Lisbon, Portugal; Sorbonne University – Paris, France; Charité – Berlin, Germany; Leiden University Medical Center (LUMC) – Leiden, The Netherlands; Ichan School of Medicine at Mount Sinai, NYC, USA; Ludger company - Oxford, UK; European Federation of Crohn's and Ulcerative Colitis Associations (EFCCA) – Belgium; and Portuguese Innovation Society (SPI) – Portugal.