RNA Cell Biology
Structural and Cellular Biology
Plant Molecular Physiology
Plants are able to perceive their surrounding light environment. Thanks to the latter, plants are able to obtain information related, for instance, to the presence, proximity and size of the neighbour plants that can compete for resources. Plants use this information provided by the light environment to adjust the shape and physiological functions of their body. In dense agricultural crops, plants shade each other and this environment has consequences on yield. The aim of our laboratory is to investigate the mechanisms used by plants to perceive and respond to the signals provided by the light environment in crops in order to help optimise crop yield.
Amyloidosis and Neurodegeneration
The main interest of our laboratory is to understand the relationship between neurodegenerative disorders (especially Alzheimer’s disease) and the accumulation of abnormal substances in the brain called “amyloid proteins”. To this end, we use a diversity of methods including the post-mortem examination of affected brains and animal models (mice, rats and flies) genetically designed to mimic some aspects of these diseases. The basic questions that higher risk of having Alzheimer’s diseases we address are: 1) why these abnormal substances accumulate? 2) are they toxic to brain cells? 3) how is the interaction between amyloid proteins and cells that determines toxicity?. On the other hand, we have started a project to search for potential genetic markers that when combined together may contribute to a higher risk of having Alzheimer in the argentine population. A better understanding of these problems will help to explore novel treatments for these diseases that, due to an increasing aging population and life expectancy, represent a public health problem of increasing magnitude
Plant Molecular Biology
When the weather is cold or warm, or light bothers us, we can look for repair, move closer to a water source or under the shade of a tree; if we lack food, we can move in its search; such behavior is a constant in the animal kingdom. However, plants are sessile, and will be in the same place in rain or snow, during hot weather or under incresing UV light, with or without wind, moisture or drought, and if food is missing there will be no option to search for it. During evolution, plants have developed remarkable acclimation mechanisms, which allow them to survive under unfavorable conditions and take advantage of the most favorable conditions. As the days get shorter before the arrival of autumn, the plants anticipate the arrival of winter; they loose leaves and protect the buds, which remain dormant until the arrival of spring. They will resist during the winter, but when the days begin to lengthen, they anticipate the arrival of spring and growth will be restored and eventually bloom, so so the fruit develops in benign conditions. If neighboring plants limit light reception, they respond by extending their stems, avoiding the shade, to get enough light (their food supply!). Plants do not move, but change their morphology in response to external stimuli. None of this would be possible without the presence of photoreceptors. Just as we have photoreceptors that allow us to see, plants have several families of photoreceptors that allow them to sense the quality and intensity of light that reach them, a measure of the presence of neighboring plants, as well as the length of the days, enabling them to anticipate the onset of winter and spring. Plants can also sense temperature, but we do not know yet the nature of the thermoreceptors. In our laboratory, we try to understand how plants perceive environmental variables such as light and temperature, and respond accordingly, modulating their development. We believe that our studies are important to develop new strategies for crop improvement, and to advance the understanding of the basic biologica mechanisms that are common to the organisms that inhabit our planet.
Circadian rhythms (circa: around, diem: day) are biological rhythms with a period close to 24h that have been described in every organism, from cyanobacteria to humans. Their presence confers clear adaptive value, allowing organisms to anticipate the daily changes in light and temperature generated by the rotation of our planet, and to adjust their behaviors and physiology accordingly. Such circadian clock keeps ticking even in the absence of day/night or high/low temperature cycles, underscoring its endogenous origin. Our lab is interested in understanding how the biological clock controls rhythms in behavior, i.e. to be awake during the day and sleepy at night. To get to these complex questions we use a powerful model system, the fruit fly Drosophila melanogaster. Drosophila is a remarkable model system because of its well-characterized development, life cycle, genetics and the availability of its full sequenced genome. Due to its short generation time, abundant progeny and efficient upbringing, the fly is an incredibly cost-effective tool to unravel complex processes that would require much more effort (in terms of time and financial support) if performed in any mammalian system. The genetics and molecular biology allow easy identification, isolation and manipulation of genes. Drosophila has not only been instrumental for the dissection of numerous signaling cascades and biochemical pathways conserved in mammals, but has also been used as model system for investigating the pathways associated with a number of human genetic conditions.
Integrative Systems Biology
The main goal of the laboratory is to understand how viral RNAs communicate with the host cell machinery and other viral components to ensure viral replication. In our research, we are using dengue virus as a model because it is one of the most important human viral pathogens of our times. Pathogenic RNA viruses, including HIV, SARS, dengue and influenza, have been the cause of the largest epidemics worldwide. Currently, neither vaccines nor antiviral drugs exist to control dengue virus infections. Our main goal is to generate knowledge and new tools to rationally design antiviral strategies. To this end, we combine biochemistry, molecular biology, and biophysics, together with classical and molecular virology studies. We use infectious dengue virus clones and manipulation of the viral genome to define the function of RNA structures and viral proteins. Using these tools in infected cells and employing reconstituted in vitro systems, we are investigating the mechanism of viral genome amplification and the process of genome encapsidation. The laboratory has made important contributions to the current knowledge of the dengue virus biology, and has developed new genetic tools to address basic questions of the viral life cycle.
Molecular Immunology and Microbiology
Cell Cycle and Genomic Stability
Cancer is a collection of cells that have acquired uncontrolled proliferative potential. These cells are very similar to the rest of the cells in our organism but the difference resides in changes of tracks of DNA which are called mutations. These mistakes (mutations) in turn, are generated as a consequence of the unfaithful duplication of DNA region(s). Mistakes are more frequent in tracks of DNA topologically altered by DNA lesions. And unfortunately, DNA lesions are very frequent and happen as a consequence of our own cellular metabolism (more than 10.000 lesions/cell daily) and increase after challenges such as sun exposure (100.000 lesions/cell in an hour). Since we cannot avoid cellular and DNA duplication (required for life itself) we need to remove lesions from DNA as fast as possible. This is done by DNA repair mechanisms. However, it is impossible to avoid the encounter of the DNA duplication machinery with at least some of those lesions. Those are extremely dangerous situations and “intelligent decisions” must be made by mechanisms that aid DNA replication in such instances. Would it be “intelligent” to kill every cell that is about to make a potencial mistake? No, it wouldn´t be, because we could loose to many cells and put tissues (and may be the whole organism) in jeopardy. Would it then be “intelligent” to preserve life and copy DNA lesions without caring about the introduction of mutation? Well, then cancer risk would increase steeply. There are many mechanisms, which are only partially understood, that make decisions at each single DNA lesions encounter by the DNA duplication machinery. These molecular decisions seek the best balance between the survival of healthy cells (with none or few mutations) and the killing of potentially dangerous cells (with higher mutagenic load). In our laboratory we study the mechanisms in charge of such decisions. We are also interested in exploring whether the disruption of such decision-maker pathways might sensitize cancer cells to the killing by agents that abruptly increase the frequency of DNA lesions such as most chemotherapeutic drugs.
Developmental Neurobiology Lab
The structure and function of proteins is crucial to understand all biological processes. The principal interest of our group is the study of proteins, including their function, evolution, structure and interaction with other molecules. Our focus is the study and development of bioinformatics tools for analysis and prediction of functionally important sites, classification and functional annotation of proteins as well as protein-protein interactions.
One of our goals is to “teach” the immune system to fight cancer using therapeutic vaccines. We work with a specialized type of immune cells called dendritic cells, which are responsible for initiating the antitumoral immune response. We study different ways to improve their action in human and murine models. We also study the tumor mechanisms responsible for immune evasion and how to revert them. In addition, we investigate cancer stem cells, which are responsible for the generation of the tumor, to find new targets and “weak points” that we can explore in order to attack cancer in a more efficient way.
Protective and Regenerative therapies of the CNS
Molecular and Cellular Therapy
Genomics studies associated with malignant progression and cellular and molecular therapy of cancer Our group is involved in the identification of genes and intracellular pathways associated with certain cancer cell types. The goal is to make use of these genes as biomarkers or novel therapeutic targets using viral and non viral-directed therapy. A) Gene identification is performed through the use of high throughput genomics and proteomics platforms using human samples (mainly in breast cancer) and cell lines with enforced expression of genetic modifiers; B) we produce nanomedicines that are retargeted using camelid nanobodies; C) we also produce onolytic adenoviruses pseudotyped with chimeric fibers, hybrid promoters, synthetic enhancers to augment viral potency and specificity. A main goal of our lab is a novel area of stem cell gene therapy that implies the target of the tumor microenvironment using stem cells as carriers of genetic medicines.
Protein Structure-Function and Engineering
Biochemistry and Molecular Biology of Development
We study molecular and physiological aspects of insects development, focusing in the holometaboulous life cycle, using Ceratitis capitata, the Mediterranean fruitly (the Medfly) and other dipterans like Drosophila melanogaster as main models. The Medfly is the main orchard pest world-wide, with significant economic importance in Argentina. Our current interest is on the study of parameters related to Functional Senescence of adults, with independence of age, using both behavioral and molecular approaches, particularly lipid profiles. We also study a novel mechanism for neurotransmitters regulation through the formation of Beta-alanine-conjugates in insect brain. The same mechanism is triggered by the innate immune response. We develop similar studies in the Hornfly, a main cattle pest and other insects.
The hippocampus is an area of the cerebral cortex that contains neural stem cells with the capacity to generate neurons through life. In our lab we investigate how adult neurogenesis contributes to hippocampal function, in particular, how newly generated neurons are develop and process information. We also investigate how these mechanisms of neural plasticity become altered under conditions such as aging and neurodegeneration.
Genetics and Molecular Physiology
Comparative Genomics of Plant Development
Molecular and Cellular Microbiology
Our goal is contribute to the understanding of how certain bacteria that are relevant for agriculture or health are capable to colonize the various niches they inhabit. We are particularly interested to determine the molecular bases of biofilm formation and adhesion to the host in species of the alpha-proteobacteria group, such as Rhizobium and Brucella. Rhizobium is a legume symbiont that is very beneficial for the plant due to its ability to fix the atmospheric nitrogen. Brucella is a close relative of Rhizobium. However, the interaction with the host results in a zoonotic disease called brucellosis, which affects cattle, pigs, and sheep, causing significant economic losses in several countries of our region. Some years ago we started another project whose objective is to explore the possibility to inactivate bacterial resistance genes and other essential genes through gene silencing approaches. The overall goal of this project is to develop a proof of concept on the use of antisense technology to extend the use of certain antibiotics or as an antimicrobial therapy per se.