Bruno Silva-Santos, Luísa Figueiredo in collaboration with Cláudio Franco, and Marc Veldhoen in collaboration with Sílvia Almeida, were awarded in the CaixaResearch Health Call 2024 to advance research in the fields of immune system modulation in response to infectious and inflammatory diseases, and host-pathogen interactions.
For this edition of the contest, which is the most important philanthropic call for biomedical research in Portugal and Spain, a total of nine groundbreaking projects were selected led in research institutions in Portugal as the Champalimaud Foundation, the i3S, ITQB NOVA, ICVS, and the University of Aveiro. This funding underscores the commitment of the “la Caixa” Foundation to champion projects of unparalleled excellence that stand to significantly benefit public health.
Read below to discover more about the projects that this funding will bring to life at GIMM.
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- Novel regulators of gamma-delta T cell subset differentiation and activation in infection
Bruno Silva-Santos
Infectious diseases like malaria or tuberculosis are still a major burden worldwide, as the available vaccines are incapable of fully preventing infection and eradicating disease. New developments require a better understanding of the immune system and how it may organise protective responses to such microbes. For many years, Bruno Silva-Santos has worked on a specific type of immune cell, the gamma delta T cells, which proliferate vigorously in response to malaria or tuberculosis. Even though these cells are associated with these diseases, for now, there are no means to manipulate their response for the benefit of the host.
In this project, now funded by the “la Caixa” Foundation, the team will identify molecules in gamma delta T cells that may become new therapeutic targets. They will focus on molecules involved in crucial processes in these cells, such as their activation and differentiation, by studying, for example, the mechanisms that allow gamma delta T cells to respond to infection through the production of special immune hormones, called cytokines. By developing this project they aim to discover new molecular strategies to mobilise the desired type of gamma delta T cell response in different pathologies that can open new and more effective strategies for controlling these challenging infections.
“This project will allow us to investigate a poorly understood immune cell subset, gamma-delta T cells, in the context of infectious diseases, aiming to boost their protective roles while reducing potentially harmful inflammatory effects. For my group, which is mostly dedicated to cancer immunotherapy, this grant will allow us to have part of the team focused on infectious diseases and thus enhance the global impact of our research”, says Bruno Silva-Santos.
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- Decoding trypanosome interactions with the host vasculature
Luísa Figueiredo and Cláudio Franco from Católica Biomedical Research Centre
Certain parasites, immune cells or tumour cancer cells travel through the blood circulation and cross blood vessels to invade organs. The parasite Trypanosoma brucei, which causes fatal diseases in Africa, crosses blood vessels, and invades various organs such as adipose tissue and the brain. This allows parasites to hide inside organs, which hampers diagnosis and worsens outcomes. In this project, the researchers aim to find parasite genes that facilitate the crossing of blood vessels, understand how the blood vessels change during infection, and elucidate the step-by-step process of parasite vascular crossing.
By collaborating with the laboratory led by Cláudio Franco in Católica Biomedical Research Centre, Portugal, which is specialised in vascular biology, the team will uncover how parasites exploit blood vessels. This knowledge may offer new treatment strategies for the diseases caused by the Trypanosome parasite, but also other pathologies that might use similar mechanisms such as cancer metastasis and inflammation.
“This grant will fund a truly interdisciplinary project bringing together the fields of parasitology and vascular biology. Understanding the role of vasculature in trypanosomiasis will allow us to better understand how this disease can be chronic for several years and escape standard diagnostic tests”, says Luísa Figueiredo.
“The “la Caixa” grant will support the productive synergy between Luísa Figueiredo’s lab and mine, at the interface between parasitology and vascular biology. This generous funding will help us uncover new mechanisms of blood vessel crossing, which could aid in treating trypanosomiasis and cancer metastasis”, adds Cláudio Franco, collaborator in this project.
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- A new strategy to modulate T-lymphocyte action and prevent hyperreactive immune responses
Marc Veldhoen and Sílvia Almeida from Co-Lab AccelBio
Infectious and inflammatory diseases, whose prevalence is increasing globally, are one of the leading causes of mortality worldwide. Many of these pathologies are related to the activity of T-lymphocytes, a type of white blood cell responsible for orchestrating the immune attack against pathogens. Sometimes, these defensive cells overreact, which can lead to the development of serious conditions such as fibrosis, chronic obstructive pulmonary disease or asthma.
Broad-spectrum immunosuppressive drugs, which target general processes, are often used to avoid these complications, but these drugs have significant side effects and increase the risk of infection. This makes it necessary to develop new therapeutic options that can selectively inhibit the activity of T-lymphocytes.
Marc Veldhoen’s team already discovered a factor that is crucial for the activation of these defensive cells. In the project now funded by the “la Caixa” Foundation, in collaboration with Silvia Almeida from Co-Lab AccelBio, experts in drug discovery, the researchers will explore this factor as a new therapeutic target to identify drugs that can modulate the T-lymphocyte response without affecting the rest of the protective immune function. This project could provide tools to avoid the common side effects when treating infectious and inflammatory diseases.
“I am very grateful to have been awarded another prestigious grant from la Caixa Health Research for our proposal, which reflects “la Caixa” Foundation’s critical support and commitment to pioneering and innovative research. This grant will enable us to advance a very promising project on controlling inappropriate T cell responses in immune-mediated inflammatory diseases”, says Marc Veldhoen.
