Mechanisms of Disease Cell Signaling
We aim to unravel how cells detect and respond to environmental changes. We focus our studies on the characterisation of stress signal transduction pathways, especially those regulated by MAP kinases of the Hog1/p38 family, also known as the stress-activated MAP kinases (SAPKs). Proper adaptation to stress involves the modulation of several basic aspects of cell biology, among them the cell cycle and gene expression. Using S. cerevisiae budding yeast as a model organism, as well as higher eukaryotic cells, we are dissecting the molecular mechanisms underlying cell response to changes in the extracellular environment and characterising the adaptive responses required for cell survival. Based on our knowledge of signal transduction and using synthetic biology, we also seek to modify cell behaviour to reprogram cell response to specific inputs/stimuli.
1. SAPK signalling: Using quantitative data in single cells and mathematical modelling, together with mutational analyses, we study the basic signalling properties of stress-responsive MAP pathways and how to alter them.
2. SAPK targets: Using proteomics, biochemistry and genetics, our main goal is to identify new targets for SAPKs and thus widen our understanding of cellular adaptation to stress. This information is expected to facilitate the characterisation of the bases of adaptation in eukaryotes.
3. Cell cycle control: SAPKs act in several phases of the cell cycle to allow prompt response to extracellular stimuli and the maintenance of cell integrity. We are uncovering the mechanisms by which Hog1 and p38 SAPKs regulate the cell cycle.
4. Regulation of mRNA biogenesis: SAPKs control critical steps of mRNA biogenesis and are thus key regulators of stress-responsive gene expression. Our main aim is to determine the contribution of multiple factors to overall gene expression in response to stress. We are also using genome-wide CRISPR screening to identify essential genes for stress adaptation.
5. Synthetic biology: We are interested in implementing complex engineered networks to perform in vivo cellular computation. In a joint effort between theoretical and experimental groups, we have established biological circuits with distributed computation. We are now addressing the application of cellular computation to relevant health issues, such as diabetes.
* shared senior authorship
- Regulation of Retinoblastoma (RB) as a newe therapeutic strategy for the treatment of breast cáncer. AECC (Spanish Asociation Against Cancer Fundation) 2018-2021.
- Transcriptional regulation by histone modifications. (BFU2017-85152-P) 2018-2020.
- Global analysis of SAPK functions in eukaryotic cells. (BFU2015-64437-P) 2016-2018.
- Systematic identification of histone marks required for transcriptional stress responses. (BFU2014-52333-P) 2015-2017.
- Molecular mechanisms under the control of SAPKs that mediate stress adaptation in eukaryotic cells. (BFU2012-33503) 2013-2015.
- Control of gene expression in response to heat stress by post-translational histone modifications in S. cerevisiae. (BFU2011-26722) 2012-2014.
- Gene expression and cell cycle control by kinases in response to stress. (BIO2009-07762) 2010-2012.
- Study of the role of chromatin in regulating induced transcription in response to heat stress. (BFU2008-00530) 2009-2011.
- Genomic instability. (Consolider) 2008-2013.
- Cell cycle control by p38 MAPK in mammalian cells. (BFU2007-66503) 2007-2010.
- Distributed Computation in Synthetic Cellular Consortia (SYNCOM). ERC Advanced Grant (7th FP) 2012-2017.
- Eukaryotic unicellular organism biology-systems biology of the control of cell growth and proliferation (UNICELLSYS). European Commission (7th FP) 2008-2013.
- Biological computation built on cell communication systems (CELLCOMPUT). European Commission (6th FP) 2007-2011.
European Science Foundation:
- Function and Regulation of SAPK Signaling Pathways in Eukaryotic Cells. EURYI 2005-2010.
- Botín Foundation (http://www.fundacionbotin.org/) 2008-2018.
- Encapsulated Synthetic Cellular Circuits to Restore Glycemic Control in Type 1 Diabetes. La Marató de TV3 2017-2019.
- Re-Configurable Biocomputing Circuits (rCBC). Office of Naval Research Global 2018-2020.
- Novel regulation of retinoblastoma (RB) creates a super-repressor for cancer treatment. UPF INNOValora - The UPF Proof-of-Concept Programme 2018.
- Distributed computation applications in biological systems for the study and application in Diabetes Mellitus. Centre per a la Innovació de la Diabetis Infantil (CIDI)- Fundació Sant Joan de Déu 2012-2016.
- INESGEN Consortium: Genomic instability. 2014-2016; 2017-2019.
- CellSYS Consortium: Developing realistic models of the different cellular processes. 2014-2016.
- Cell Signaling Research Group (SGR; Catalan Government) 2017 SGR 799.