Every year the Konex Foundation rewards an activity different from Argentine culture, and in 2023 it is the turn of the science and technology. No less than one hundred winners from 21 disciplines will be recognized on September 12 at the Assembly Hall of the Faculty of Law of the University of Buenos Aires (UBA). One of those disciplines is Biochemistry and Molecular and Cellular Biology. And there are five Argentine scientists whom the jury decided to highlight for their work in the last decade: Beatriz Caputto, Diego de Mendoza, Marcelo Rubenstein, Alexander Schinder and Alejandro Villa. Passionate and passionate, they described NEWS What are the axes of your research?
lipids
Beatriz Caputtoformer president of the Argentine Society for Research in Biochemistry and Molecular BiologyProfessor and Professor Emeritus of the National University of Cordoba (UNC) and Senior Researcher at CONICET. His track record includes discovering new roles for the c-Fos protein, which regulates key mechanisms for membrane genesis by controlling lipid metabolism.
“The supply of lipids is an essential requirement for cell differentiation, proliferation and growth, since lipids are the most abundant components of biological membranes. A characteristic of tumor cells is their exacerbated cell growth, which requires a very high rate of lipid synthesis,” Caputto explained to NOTICIAS. It is because of this characteristic that Caputto and his team decided to study the synthesis of lipids and their relationship with c-Fos in tumor cells: they found that one hundred percent of the malignant human brain tumors examined (in more than 250 biopsies) and the 99 percent of human breast malignancies examined (more than 210 samples) show abnormally high c-Fos content.
“In addition, this protein is associated with the lipid synthesis machinery and is essential for accelerating tumor growth. If we decrease the c-Fos content in tumor cells or block its ability to activate lipid synthesis, tumor cells grow significantly slower or stop growing. These and other results have led us to postulate c-Fos as a new target to develop antitumor therapies since the control of the expression of c-Fos or its capacity to activate the synthesis of lipids makes it possible to regulate the uncontrolled growth of tumor cells”.
However, warns the researcher, “you have to be very prudent and do not create false expectations because still there is a long way to go so that these results can be translated into a new therapy that can be applied in cancer patients”.
Another of the scientists recognized this year with the Konex Award also works on lipids, but in a completely different line. Is about Diego de Mendozawho already in 2003 received the Konex Award for his research within the Cytology and Molecular Biology discipline.
Diego de Mendoza’s group carries out experiments with a model organism, the tiny worm called C. elegans. “These little worms, only one millimeter long, are a very useful tool because, although it may not seem like it at first glance, They look a lot like humans: have neurons, skin, gut, muscle, and other tissues that are similar in shape, function, and genetics. For this reason, they can be used to deepen the knowledge of certain human diseases of genetic origin”, describes the researcher, who is Honorary Professor of the National University of Rosario and Senior Researcher hired by CONICET at the Institute of Molecular and Cellular Biology of Rosario (IBR).
One of the laboratory’s achievements was the discovery that certain neurotransmitter lipids called endo-cannabinoids can release cholesterol trapped in the tissues of C. elegans due to a mutation. “This mutation, in humans, is the cause of a neurodegenerative genetic disease called Niemann Pick. Also, using this same little worm, we intend to elucidate the mechanism by which disturbances in lipid metabolism are involved in the pathogenesis of Parkinson’s disease”, concludes de Mendoza.
neurons
CONICET Senior Researcher and Director of the Neuronal Plasticity Laboratory at the Leloir Institute Foundation, Alexander Schinder leads a team investigating the process by which the hippocampusregion of the brain involved in learning and memory, generates neurons throughout life. Something that was already believed in the 1960s but was reinforced and verified until the early 2000s.
The brain acquires, processes, and stores information through its neural circuits, huge networks of interconnected neurons that receive and send electrical signals. “Initially it was not believed that it was possible to regenerate neurons -explains Schinder, also awarded with the Konex 2023-, but in the 90s it was discovered that neurons do not duplicate, but the brain contains stem cells capable of producing neurons throughout life. This occurs continuously in the healthy hippocampus, but there are other areas of the brain that can also produce neurons under very specific pathological conditions. In recent decades we have been able to better understand that these new neurons are used to process information in a different way to which all the other neurons generated during early brain development do.”
What is the difference? That each new neuron goes through its own development process, through which it changes its characteristics until it reaches full maturity. This development occurs over a very long period of weeks to months, which is very long for the times that the brain handles. “During this period, the neuron grows, establishing connections with different circuits and changing the way in which it processes information,” concludes Schinder. This kind of plasticity is so special because it gives the adult hippocampus a dynamism that doesn’t occur in any other circuitry in the brain.”
Appetite and bacterial resistance
Marcelo Rubenstein is an Associate Professor of Department of Physiology, Molecular and Cellular Biology (FCEyN, UBA) and Director of the Institute for Research in Genetic Engineering and Molecular Biology (INGEBI-CONICET). His research has allowed him to decipher key components linked to appetite.
Food intake and energy balance are highly regulated by neural circuits that are highly conserved at the genetic, anatomical, and functional levels in all vertebrate animals. These circuits originate very early during the embryonic development of the mammalian brain following specific genetic programs that determine the identity of each group of neurons in distinctive neuroanatomical positions. “In my laboratory we have discovered in recent years multiple genetic components that interact synergistically in neurons whose activity is essential to avoid food overflows Rubinstein describes. We found that mutations in each of these genetic components induces an exaggerated increase in caloric intake with the consequent development of obesity.
But Rubinstein is also co-founder of the Argentine Network of Medicinal Cannabis of the CONICET. “The endocannabinoids They are a very particular type of neurotransmitters (molecules that establish communication between neurons) produced by our brain, which are distinguished by having a unique mechanism of action and by stimulating specific receptors that can also be activated by molecules present in the cannabis plant”. Explain. In recent years, various laboratories have shown that the endocannabinoid system regulates a multiplicity of brain circuits related to cognitive, motor, emotional and sensory functions and that phytocannabinoids have medicinal properties.
Alejandro Villain turn, is distinguished by its Pioneering work in the application of Nuclear Magnetic Resonance in structural biology in Argentina. His group is one of the most important internationally in the study of bacterial resistance to antibiotics, and the development of strategies to control it, and the mechanisms of transport and storage of metals in biological systems.
Professor of Biophysics at the National University of Rosario (UNR), Senior Researcher at CONICET and head of the Structural and Metabolomics Biology Platform at the Institute of Molecular and Cellular Biology of Rosario (IBR), Vila and his group are world leaders in the study of resistance to antibiotics mediated by certain enzymes: metallo-β-lactamases, which they began to study 25 years ago. These substances became one of the main mechanisms of antimicrobial resistance, giving rise to the so-called “superbugs”.
Vila’s work allowed us to understand the mechanism and evolution of resistance guided by these proteins, and identified new dissemination mechanisms among pathogenic bacteria. His group is currently part of an international consortium funded by the United States Institutes of Health (NIH) that designs inhibitors that allow extending the useful life of antibiotics currently in use.
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