Paradigms of survival in Leishmania parasites, Prof. Dr. Alicia Ponte-Sucre

Summary

The Molecular Physiology Laboratory was created in 1994, a few months upon the return of Alicia Ponte-Sucre (APS) to the Chair of Physiology, after completing her Doctorate in Sciences at the Central University of Venezuela. Although the academic career of APS had begun in 1981, when she joined the Department of Physiological Sciences, Faculty of Medicine, UCV as an Instructor, it was at the end of her doctorate when she decided to become independent and organized her research group. The leitmotif of the Molecular Physiology Laboratory has been to understand fundamental processes involved in essential functions related to homeostasis and preservation of life. The main focus in their research has been understanding the physiological mechanisms responsible for drug- susceptibility/resistance, in the metabolically flexible parasites such as Leishmania and to a lesser extent Trypanosoma. The comprehensive approach that this laboratory has made in this field of health research is based on the training that APS, as well as her colleagues, have in multiple areas of knowledge including, biochemistry, biophysics, cellular biology, physiology and pharmacology. In 1988 when APS began her doctorate, she decided to direct her research towards this area of ​​knowledge, closely related to health and development, that constitute important challenges in areas of the world that include her country of origin, Venezuela. Since then, her laboratory has focused on the understanding the physiology and exploring the pharmacology of neglected tropical diseases (NTDs), such as leishmaniasis and trypanosomiasis, produced by the unicellular parasites Leishmania and Trypanosoma. This short article summarizes the scientific production, teaching activities, and services provided by the Molecular Physiology Laboratory upon reaching 25 years of existence.

Key words: Leishmania, Trypanosoma, Molecular Physiology, Neglected Diseases

Introduction

Search for knowledge identifies human beings. Since ancient times, the how and why of the surrounding world are challenging questions. The seventeenth century represented a hallmark with the improvement of the scientific method. Since then, human beings began to systematically accumulate knowledge and build human capacity, behaviors that favor the optimization of our environment and destiny. Consequently, scientists assumed great responsibility before society. Doing science (being curious and searching for answers) is incorporated into our DNA. This condition exalts our human trait, and creating knowledge expands our horizon to improve the living conditions of the society in which we are immersed.

Since the second half of the twentieth century the complexity of doing science has increased significantly, in line with the scale of the challenges we dare to face. The consequence has been the conformation in the 21st century of large-scale collaboration models, or “Big Science.”  (1) Large-scale science complements the creative work of individual researchers, who explore the limits of nature; Big Science is based on concepts, techniques, instruments and reagents that, in a coordinated and systematic way, identify challenges whose solution exceeds the strengths of an individual researcher.

An example of this, from a global perspective, refers to one of the best examples of international solidarity of the 21st century, the decision taken by the 193 member states of the United Nations in 2000 to approve the Millennium Development Goals (MDGs) ), subsequently extended for the 2015-2030 period to the Sustainable Development Goals (SDGs). In 2000, the international community committed itself to working together and coordinating efforts to achieve a better world by 2015 (2, 3) and later by 2030. (4) The MDGs catalyzed coordination, research and solidarity efforts without precedents, thus exposing the best of our human condition.

Three of the eight MDGs are directly related to the area of ​​health. ODM-4, ​​ODM-5 and ODM-6, and ODM-8 to research and development. However, despite the enormous effort invested so far, 5 years after leaving 2015, we are far from achieving the MDGs globally. (5) In this arduous mission researchers and academics carry out tasks of great commitment, linked to the possibility of improving the living conditions of the society, including health. It is in this subject where my professional life is inserted.

As a graduate of the Andrés Bello Catholic University, School of Education, Venezuela, my academic career began formally in 1981, upon entering the Department of Physiological Sciences, Faculty of Medicine, UCV as an Instructor (equivalent to Assistant Professor). I joined this Chair after completing my studies at the Venezuelan Institute of Scientific Research (IVIC) and graduating from the Magister Scientiarum in Biology, mention Physiology and Biophysics. I initiated the Molecular Physiology Laboratory (LFM) in 1994, a few months upon returning to the Chair of Physiology, after completing my fourth level of studies and obtaining the degree of Doctor in Sciences (Pharmacology, 1993, UCV). Since 1988, when I started my doctorate, I oriented my research interest towards issues related to health and sustainable development. The laboratory studies leishmaniasis and trypanosomiasis, neglected tropical diseases (NTDs), produced by the single-celled parasites Leishmania and Trypanosoma.

Control and prevention of these diseases is closely related to experimental research, due to the urgency of establishing adequate diagnoses and offering optimal chemotherapies, achieving appropriate control and/or elimination of vectors and, optimizing guidelines to be applied in epidemiological, sociocultural and health contexts, common in areas of the world where these diseases are endemic. The organisms that cause these conditions are extremely flexible and have sophisticated survival mechanisms, implying that the challenge we face indicates that our work must produce useful knowledge for solving the ailments caused by these parasites.

The leitmotif of the LFM has been to understand fundamental processes involved in essential functions related to homeostasis and preservation of life, with a focus on the study of the mechanisms responsible for drug- susceptibility, or resistance, in these metabolically flexible parasites. The integral approach of the LFM has been based on the training of its members in areas including biochemistry, biophysics, cell biology, physiology and pharmacology.

But why physiology of parasites? Physiological sciences are an example of integration in which knowledge is organized according to broad and specialized interests. A physiologist, to study the mechanism of action of a drug, or the processes involved in parasite-host interaction, or the cellular mechanisms triggered in a parasite during the adaptation phenomena that support its survival at very high doses of chemotherapy, uses biochemical, histological, biophysical and physiological methods. The obtained results derive from concepts that could eventually be associated with the pathophysiology of the disease and the clinic outcome, according to the general principle of Claude Bernard (1859): It is necessary to raise first of all the medical problem as it is given by the observation of the disease, and then experimentally analyze the pathological phenomena trying to give their physiological explanation.

This implies a conceptual identity between biochemistry, physiology, pathology and pharmacology. At the same time this illustrates the perpetuation of the classical separation of these disciplines in the curriculum of medical studies, based on the intrinsic value of each, without affecting the object of inquiry of the physiological sciences as a whole (6), the function of an organism. As we believe in a transdisciplinary and interdisciplinary university, in which frontiers of knowledge surpass dogmatic canons, our research is consistent with these integration concepts.

This scheme includes teaching-learning methods based on the analysis of the philosophy of the medical science itself, as the "epistemology of interdisciplinarity", in tune not only with innovation, but with specific circumstances, such as break points of educational institutions, health centers (7), and in a Faculty of Medicine, as is the case. Therefore, among those who "do" physiological sciences, physiologists take the lead in how to link the other disciplines that make up the organization chart and integrate them. (7) This constitutes a natural process since physiological systems are only a context (organism, tissue, cell), where chemical processes (biochemistry), are regulated by molecules (pharmacology), and under strict control (functional feed-back loops), which if altered (pathology), break the physiological dynamics. This conceptual identity guides the research presented here around a concrete subject, the flexibility of Leishmania.

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