Research lines
1. Phase separation in the cell nucleus and transcription factors
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In diverse cell types there is a variety of subcompartments with specific properties and functions but not delimited by biological membranes as most cytoplasmic organelles.
In recent years, accumulated evidence suggested that these subcompartments form by a liquid-liquid phase separation process. This constitutes an important, revolutionary shift in the paradigm related to intracellular organization.
In this context, compartmentalization may favor certain biochemical reactions by locally increasing the concentrations of reactants, modulate the speed of reactions due to different properties of liquid phases, and work as storage centers to facilitate or inhibit certain reactions.
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Biophysics-related literature and our results support the hypothesis that the distribution of transcription factors between different nuclear compartments modulates indirectly the interaction of these biomolecules with their DNA targets and, therefore, the transcriptional response.
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For this reason, we explore the heterogeneous nuclear distribution of certain transcription factors and study their network of interactions within the cell nucleus. In these studies, we focus in two model systems with biomedical relevance:
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a) Action of key transcription factors for mantainence of fundamental properties of pluripotent stem cells.
Pluripotent stem cells have the ability to multiply unlimitedly in culture and differentiate to every cell type of the organism, re-capitulating the properties of primitive cell of the embryo. This determines that these cells are an important promise in the area of regenerative medicine.
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b) Action of the glucocorticoid receptor
This receptor is a ligand-activatable transcription factor, particularly by glucocorticoids. These compounds play a relevant physiological role with diverse effects in the organism. They are used as drugs by their anti-inflammatory effects.
2. Cytoskeleton organization and function in transmission of mechanical signals
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The ability of an eukaryotic cell to resist deformation, transport organelles and vesicles and change shape during cell migration depend on cytoskeleton and reglatory proteins in constant remodelling. Internal and external physical forces may act through the cytoskeleton to locally modify the mechanical properties and cell behavior. For this reason, it is very important to understand how the cytoskeleton networks are capable of generate, transmit and respond to mechanical signals thus affecting shape, function and cell destiny.
3. Function of molecular motors in intracellular transport
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The intracellular transport of small molecules and larger particles such as organelles is essential for cell function. However, the principles behind this transport are unknown.
While small molecules can move through the cytoplasm through diffusion, organelles and vesicles require an active transport system involving polymerized filaments (i.e. actin filaments and microtubules) and molecular motores (i.e. myosin, kinesin and dynein). These latter ones use energy provided by ATP hydrolysis to move in discrete steps along filaments. The interest in motors has grown in the last years since they rule the directed transport of macromolecules, biological membranes and chromosomes, necessary for cell viability.