A5031891630- Gene Regulatory Network Analysis
- Fungal and yeast genetics research
- Single-cell and spatial transcriptomics
- RNA and protein synthesis mechanisms
- Cell Image Analysis Techniques
- Microbial Metabolic Engineering and Bioproduction
- Advanced Fluorescence Microscopy Techniques
- PI3K/AKT/mTOR signaling in cancer
- Bioinformatics and Genomic Networks
- RNA Research and Splicing
- Receptor Mechanisms and Signaling
- Genomics and Chromatin Dynamics
- Neurobiology and Insect Physiology Research
- Bacterial Genetics and Biotechnology
- Reproductive Biology and Fertility
- Monoclonal and Polyclonal Antibodies Research
- Nuclear Structure and Function
- Estrogen and related hormone effects
- Microtubule and mitosis dynamics
- Cell Adhesion Molecules Research
- Lipid Membrane Structure and Behavior
- Neuroendocrine regulation and behavior
- Plant Reproductive Biology
- Reproductive System and Pregnancy
- Neuroscience and Neuropharmacology Research
Fundación Ciencias Exactas y Naturales
2015-2025
University of Buenos Aires
2015-2025
Instituto de Neurología de Buenos Aires
2018-2025
Institute of Astronomy and Space Physics
2018-2025
Consejo Nacional de Investigaciones Científicas y Técnicas
2014-2024
Centro Científico Tecnológico - San Juan
2022-2023
Fred Hutch Cancer Center
2016
Czech Academy of Sciences, Institute of Physiology
2014
Instituto de Cardiología y Cirugía Cardiovascular
2013
Experimental Medicine and Biology Institute
1995-2011
The phosphorylation and dephosphorylation of proteins by kinases phosphatases constitute an essential regulatory network in eukaryotic cells. This supports the flow information from sensors through signaling systems to effector molecules ultimately drives phenotype function cells, tissues, organisms. Dysregulation this process has severe consequences is one main factors emergence progression diseases, including cancer. Thus, major efforts have been invested developing specific inhibitors...
Cells make decisions based on a combination of external and internal signals. In yeast, the high osmolarity response (HOG) is mitogen-activated protein kinase (MAPK) pathway that responds to variety stimuli, it central general stress response. Here we studied effect heat-stress (HS) HOG. Using live-cell reporters genetics, show HS promotes Hog1 phosphorylation Hog1-dependent gene expression, exclusively via Sln1 phosphorelay branch, strength activation larger in yeast adapted osmolarity....
Although the proteins comprising many signaling systems are known, less is known about their numbers per cell. Existing measurements often vary by more than 10-fold. Here, we devised improved quantification methods to measure protein abundances in Saccharomyces cerevisiae pheromone response pathway, an archetypical system. These limited variation between independent of abundance a factor two. We used these together with quantitative models identify and investigate behaviors system sensitive...
Cells continuously sense their surroundings to detect modifications and generate responses. Very often changes in extracellular concentrations initiate signaling cascades that eventually result gene expression. Increasing stimulus strengths can be encoded increasing concentration amplitudes or activation frequencies of intermediaries the pathway. In this paper we show different way which amplitude frequency encoding map environmental endow cells with qualitatively information transmission...
We selected peptide aptamers from combinatorial libraries that disrupted cell-cycle arrest caused by mating pheromone in yeast. used these as baits two-hybrid hunts to identify genes involved arrest. These experiments identified known function the pathway, well a protein kinase, CBK1 product, whose was not known. modified system specific interactions aptamers. demonstrate means perform "genetics" on complement of cell without altering its genetic material. Peptide can be disrupt process....
Crosstalk between MAPK pathways activated by a single sensory input enhances yeast responses to multiple simultaneous stimuli.
Studies of cell-to-cell variation have in recent years grown interest, due to improved bioanalytical techniques which facilitates determination small changes with high uncertainty. Like much high-quality data, single-cell data is best analysed using a systems biology approach. The most common approach the standard two-stage (STS) In STS, from each cell separate sub-problem, meaning that only same used calculate parameter values within cell. Because parts are considered, problems...
Abstract According to receptor theory, the effect of a ligand depends on amount agonist–receptor complex. Therefore, changes in abundance should have quantitative effects. However, response pheromone Saccharomyces cerevisiae is robust (unaltered) increases or reductions G‐protein‐coupled ( GPCR ), Ste2, responding instead fraction occupied receptor. We found experimentally that this robustness originates during G‐protein activation. developed complete mathematical model step, which suggested...
Using a model of medroxyprogesterone acetate (MPA)-induced mouse mammary tumors that transit through different stages hormone dependence, we previously reported the activation phosphatidylinositol 3-kinase (PI3K)/AKT (protein kinase B) pathway is critical for growth hormone-independent (HI) carcinomas but not hormone-dependent (HD) carcinomas. The objective this work was to explore whether PI3K/AKT responsible changes in tumor phenotype and transition autonomous growth. We found inhibition...
Akt/PKB is a key signaling molecule in higher eukaryotes and crucial protein kinase human health disease. Phosphorylation, acetylation, ubiquitylation have been reported as important regulatory post-translational modifications of this kinase. We describe here that Akt modified by SUMO conjugation, show lysine residues 276 301 are the major attachment sites within protein. found phosphorylation SUMOylation appear independent events. However, decreasing levels severely affects role regulator...
Significance Many cell decisions depend on precise measurements of external ligands reversibly bound to receptors. Yeast cells orient in gradients sex pheromone detecting differences the amount ligand-receptor complex. However, yeast can with nearly all receptors occupied. We describe a general systems-level mechanism, pre-equilibrium sensing and signaling (PRESS), which overcomes this saturation limit by shifting expanding input dynamic range respond. PRESS requires that events downstream...
The gradient of Bicoid (Bcd) is key for the establishment anterior-posterior axis in Drosophila embryos. properties are compatible with SDD model which Bcd synthesized at anterior pole and then diffuses into embryo degraded a characteristic time. Within this model, diffusion coefficient critical to set timescale formation. This has been measured using two optical techniques, Fluorescence Recovery After Photobleaching (FRAP) Correlation Spectroscopy (FCS), obtaining estimates FCS value an...
The protein kinase Akt/PKB participates in a great variety of processes, including translation, cell proliferation and survival, as well malignant transformation viral infection. In the last few years, novel Akt posttranslational modifications have been found. However, how these modification patterns affect subcellular localization, target specificity and, general, function is not thoroughly understood. Here, we postulate experimentally demonstrate by acyl-biotin exchange (ABE) assay 3...
The unfolded protein response (UPR) and the Akt signaling pathway share several regulatory functions have capacity to determine cell outcome under specific conditions. However, both pathways largely been studied independently. Here, we asked whether regulates UPR. To this end, used a series of chemical compounds that modulate PI3K/Akt monitored activity three UPR branches: PERK, IRE1 ATF6. antiproliferative antiviral drug Akt-IV strongly persistently activated all branches We present...
The process of embryo implantation requires extensive remodelling the endometrial extracellular matrix, a function largely performed by matrix-degrading metalloproteinases (MMPs). In present study, we used trophoblast cells isolated from human term placentas to study regulation MMPs nitric oxide (NO). Using combination zymography, Western blot and indirect immunofluorescence, showed that MMP-2 MMP-9 are increased during conversion low-motile cytotrophoblast highly motile differentiated...
Ultrasensitive response motifs, capable of converting graded stimuli into binary responses, are well-conserved in signal transduction networks. Although it has been shown that a cascade arrangement multiple ultrasensitive modules can enhance the system’s ultrasensitivity, how given combination layers affects cascade’s ultrasensitivity remains an open question for general case. Here, we introduce methodology allows us to determine presence sequestration effects and quantify relative...