Sysbio:Research
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ResearchSingaling networks and cancerSmall molecule inhibitors display significant potential as treatment for diseases and cancer progression involving deregulated signal transduction pathways. These inhibitors are developed based on their target specificity and binding affinity. We focus on the fact that the numerous signaling proteins and feedback loops in signaling pathway strongly influences the efficiency of combinatorial small molecule inhibitor treatments. The existence of several regulatory positive and negative feedback loops either creates complex dose-responses, desensitization to periodic treatments, or modulation of the drug effect in combinatorial treatments. Our experiments show that the effect of inhibitors strongly depends on the particularities of the architecture of the targeted pathway, which must then be taken into account when designing treatments to inhibit pathogen nonlinear pathways.The nonlinear characteristics of the interaction between the proteins ultimately dictates the dynamics and response to drug treatment.
Regulation of Stem Cell Differentiation The cellular machinery is governed by interacting proteins, genes and metabolites that form complex and highly interconnected networks of interactions. This way, extracellular stimuli triggers pathways of biological events that regulate gene expression, protein activity, and ultimately, cell response. The transforming growth factor (TGF-ß) pathway is one of the most conserved and prolific of these signaling cascades, involved in a wide variety of both adult and embryonic processes. We use in vivo experiments and theoretical approaches to understand how the wiring of the pathways determines the role of the proteins that regulate neurogenesis. Therefore, to understand the regulation of neuronal formation it is not sufficient to understand the function of each of the proteins in the pathway. A deep understanding of the consequences of the nonlinear wiring of the pathway is required to understand stem cell fate decision and embryogenesis.
Regulation of ligand-receptor systems Cells translate extracellular information into internal responses using surface-receptors embedded in the plasma membrane. A cell surface-receptor is a highly specialized integral membrane protein that binds to a specific family of ligands, including cytokines, neurotransmitters, peptide hormones or growth factors. The interaction of ligand and receptor initiates a chain of intracellular events and biochemical reactions referred as signal transduction, leading to physiological changes and regulating essential cell processes, such as differentiation, development, proliferation or apoptosis. The understanding of the regulation of cell-surface receptors and the interaction with their corresponding ligands constitutes an extremely active area of research, mainly due to their pharmacological importance as selective targets for chemotherapeutic agents. At present, receptors-based drugs represent more than 60% of medicines in the market, designed to treat several diseases like autoimmune illnesses, infectious diseases or even cancer. We use a mathematical approach to unveil the consequences of the complex binding process and its relevance in the regulation of the signaling.
Synthetic BiologyWe use a synthetic biology approach to understand basic biological processes, engineering cells to exhibit a desired behavior that allow us to study regulatory mechanism such as cell division, transcription and translation. In detail, we implement nonlinear network motifs in mammalian cells to determine the dynamics of gene interaction networks.
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