Inflammation is an answer to infection or tissue damage that occurs to eradicate microorganisms or irritating agents and to potentiate tissue repair. When excessive or persistently activated, inflammation can cause commitment of organs and systems, leading to decompensation, organic dysfunction, and death. Currently, it is recognized that inflammation is involved in different diseases, infectious or not, understanding diseases caused by protozoans and bacteria, osteoarthritis, cardiovascular system diseases, neuropathies, pulmonary diseases, multiple sclerosis and cancer, which generate, every year , high cost to health systems in the country. Despite this knowledge, the cellular and molecular mechanisms involved in the pathogenesis of these diseases are not fully elucidated, which leads to diagnostic limitation and application of more effective therapies. Thus, the continuous investment in research and training of human resources in the technical / scientific field is fundamental for the advancement of the identification of new targets for the development of more effective therapeutic strategies to the treatment of these inflammatory natural diseases. In this context, the research currently developed in this institution, in the field of inflammation, encompass three main issues: 1) molecular and cellular bases of inflammatory diseases; 2) identification of molecular targets involved in inflammatory diseases and 3) development of treatments and therapies for inflammatory diseases. In view of the complexity of this theme, activities that promote the internationalization of our Institution will contribute strongly to the extension of knowledge, establishment of new technologies, disclosure and exchange experiences with other centers of excellence in that area of knowledge. In addition, we stress that the internationalization process will encourage the strengthening and establishment of new external partnerships, by exchange of faculty and students, achievement of courses, workshops and symposia, which contribute to the enhancement of highly trained staff and involved in the development of research in this theme.
- Molecular and cellular bases of inflammatory diseases
In this line of research it will be contemplated studies aimed at clarifying the mechanisms underlying the participation of inflammatory mediators in psychopharmacological conditions and the establishment of the inflammatory process from the cell to the organ, in different pathological conditions. Inflammation is present in several pathological processes and has been an important therapeutic target; however, our understanding of how to establish and whether inflammation is the cause or consequence of the pathological process is still limited. In this sense, in our institution several research groups are already developing studies that have thes main to investigate the mechanisms and systemic repercussions of inflammation. The present proposal is convergent in the sense of grouping these different institutional groups with multidisciplinary and translational characteristics, as well as include international collaborators of recognized reputation in the area who will allow the advancement in scientific knowledge and innovation, besides promoting the formation of human resources of high quality and advance in internationalization. The main topics to be addressed are molecular, cellular, functional, and integrative mechanisms related to inflammation in various experimental models (in vitro, in vivo, in situ, ex vivo) including: cardiovascular, respiratory, renal, metabolic diseases (obesity and diabetes), infectious bacterial or parasitic, neurodegenerative, autonomic and hematological, endocrine and reproductive. The aim is to identify the acute and chronic molecular mechanisms of inflammation, its repercussions and interactions, investigating processes such as autophagy, inflammasome, protein acetylation, epigenetic changes, angiogenesis, oxidative stress, neurohumoral alterations, repercussions of interventions such as physical exercise, diet and nutraceutical effect, innate immunity, signaling network of nuclear receptors, among others. One focus will be the translational approach, for example, the study of patients undergoing cardiac surgery and revascularization, as well as patients with inflammatory diseases of the male reproductive tract and those with sickle cell disease. It is important to highlight that the development of this subproject entitled “Molecular and cellular bases of inflammatory pathologies”; will be important and convergent to the other two subprojects involved in the present proposal.
- Identification of molecular targets involved in inflammatory diseases
In this area of knowledge, the studies are aimed at understanding the actions of mediators of various natures and the characterization of biological targets, or biomarkers, involved in inflammatory disorders or diseases, aiming at the development of new drugs with anti-inflammatory activity. These studies are part of two research fronts: 1) studies of the pathophysiological role of anti- and pro-inflammatory agents and their molecular mechanism on the cellular response in certain organs or systems; 2) identification and characterization of pharmacological targets or exogenous compounds, with potential regulatory effect on the inflammatory response. For this, experimental protocols are used in vivo and in vitro, which include models of acute inflammation of tissue and dermatological lesions and of chronic inflammation of the airways, neural and sensorial. Also, molecular biology, microscopic and functional techniques are used, as well as analysis of systems biology, such as metabolomics and lipidomics.
- Development of treatments and therapies for inflammatory diseases
Acute inflammation is defined as the human body’s immune reaction aimed at defense against foreign elements - these include microorganisms and toxins. This process occurs in several stages (being single or multiple) with lesions and tissue repairs in search of return to the normal physiological state. Not infrequently, in mild to moderate inflammatory processes of short duration, tissue repair occurs without sequelae, however, severity with chronicity of the inflammatory process can lead to tissue changes of various degrees and contribute to the induction of various diseases, the bankruptcy of the affected organs and even the death of the patient. This project aims to the physiopathological understanding with a focus on the treatment and development of therapies of several types of inflammatory diseases, which include ischemic diseases (eg, cerebral, cardiac, limb and sensory structures of the inner ear); respiratory diseases caused by environmental pollution, allergies; metabolic diseases (such as diabetes and its consequences) and toxic (ex: accidents with toxins from venomous animals). Thus, taking advantage of the knowledge generated by research in basic and translational sciences, we intend to develop therapies based on the modulation of genes that control the activity of inflammatory cells (such as monocytes and macrophages), the use of stem cells among other approaches that aim potential anti-inflammatory and regenerative treatments.
Partner countries: Canada; Australia; United Kingdom; Italy; Norway; Germany; U.S; France; Chile; Costa Rica; Portugal.