“la Caixa” Foundation supports projects in Leukemia, the immune system, and antibiotic resistance
Improving the quality of life of survivors of T lymphocyte leukemia, developing immunotherapies for the treatment of infectious diseases, and combating antibiotic resistance are the main objectives of the three projects led by i3S researchers who have just been awarded funding from the 6th CaixaResearch Competition of Health Research 2023, promoted by the “la Caixa” Foundation in partnership with the Foundation for Science and Technology (FCT).
These three i3S proposals are among a total of 33 (Portuguese and Spanish) research projects in biomedicine and health considered to be of excellence, which will receive more than 25 million euros over the next three years. Of the 152 Portuguese applications presented, 11 were selected and, as a whole, will be financed with 7.9 million euros.
Around one million euros will be invested in the project led by Nuno Rodrigues dos Santos called “Deciphering the effect of leukemia on the immune system beyond the disease” which is a consortium between the i3S group led by Nuno Alves with the Center of Molecular Biology Severo Ochoa (“Consejo Superior de Investigaciones Científicas”) in Spain, and with the University of Oxford from the United Kingdom. The project led by Nuno Alves focuses on improving the design of immunotherapies for the treatment of infectious diseases, immunodeficiencies and tumors and will be financed with 500 thousand euros. The same amount was allocated to the proposal presented by Didier Cabanes, which aims to find new strategies to combat antibiotic resistance.
Improving the immune system of leukemia survivors
Leukemia is the most common cancer in children under 14 years of age and T lymphocyte leukemia, in particular, affects 20 to 35 children per one million inhabitants. Thanks to current treatments the remission rate is more than 80% in children and 50% in adults - however, survivors often develop immunological diseases later in life. Because of this Nuno Rodrigues dos Santos says “it is essential to understand how, when and why diseases or immunological disorders develop as a consequence of the original leukemia. Recent studies indicate that this is due to the effects of leukemia on the bone marrow and thymus, the organs where B and T lymphocytes, two types of immune cells, are formed”.
This project, explains the researcher, will make use of genetically modified mouse models that replicate the development, treatment and remission of T lymphocyte leukemia. The objective is to “understand how leukemic cells affect the regeneration, maintenance and function of the immune system during the disease and after remission”. In addition to the known toxic effects of chemotherapy treatments, it is essential to distinguish between the direct effects of leukemia and those caused by chemotherapy. The ultimate goal is to “pave the way for the design of new therapies targeting the immune system that improve the quality of life of survivors”.
Control the functioning of the thymus gland
Also in the area of the immune system, the project led by Nuno Alves focuses on the study of the molecular mechanisms that regulate the production of T lymphocytes and their implications for the response against infectious diseases. T lymphocytes are immune cells in the blood that become less effective in fighting infections and responding to vaccines as they age. As T lymphocytes are produced in the thymus, this organ plays an essential role in establishing antimicrobial immune responses. The deterioration of thymus function that occurs with age has significant negative consequences for older people and people who are immunocompromised, such as cancer patients or people who have recently received a bone marrow transplant.
Within the scope of this project, explains Nuno Alves, “we want to understand the molecular mechanisms that regulate the production of T lymphocytes in the thymus with the aim of controlling the functioning of this organ”. The knowledge “will be used to improve the design of immunotherapies for the treatment of infectious diseases, as well as immunodeficiencies and tumors”. To achieve this goal, the team will investigate at various levels, from cellular analysis to the study of infection models in mice, with the aim of better understanding the function of the thymus in vivo.
Two ways to attack super-resistant bacteria
The project coordinated by Didier Cabanes focuses on one of the biggest health challenges of the 21st century: antibiotic resistance. Gram-positive bacteria, such as staphylococci, enterococci, and streptococci, represent a serious threat to public health and, although antibiotics can eliminate some microorganisms, the truth is that they also contribute to the emergence of resistant bacteria, which can proliferate without control. At the same time, the researcher emphasizes, “there is also a stagnation in the development of new antibiotics”.
For these reasons, and also to preserve the human microbiota, which is essential for health, underlines Didier Cabanes, “alternative therapeutic strategies to antibiotics are being sought which may, for example, aim to decrease the virulence of microorganisms or ‘resensitize’ resistant bacteria so that they become susceptible again to available antibiotics”.
In previous studies, the team led by Didier Cabanes demonstrated that certain specific glycopolymers present in the cell wall of gram-positive bacteria are crucial not only for bacterial pathogenicity, but also for their resistance to host defenses and antibiotics. With the current project, the researchers aim to “decipher the molecular mechanisms involved in this process, in order to develop new medicines that, by inhibiting cell wall glycosylation, simultaneously reduce the pathogenic capacity of bacteria and increase their susceptibility to the host’s immune system and the action of antibiotics”.
About the CaixaResearch Health Research Awards
The CaixaResearch Health Research Competition was created in 2018 with the aim of supporting basic, clinical and translational research projects of scientific excellence and with social impact in the study areas of cardiovascular and infectious diseases, oncology, and neurosciences, as well as projects that develop enabling technologies in these areas. Since the beginning of the Program, the competition’s funding has totaled 120.5 million euros for 171 projects, 117 of which are led by Spanish teams and 54 by Portuguese research groups. In Portugal, the initiative is carried out in collaboration with the Foundation for Science and Technology (FCT), belonging to the Ministry of Science, Technology and Higher Education, which funded 5 of the 11 Portuguese projects selected in this edition with 2.3 million euros.