SignalYeast: Cell Signaling and Synthetic Biology in Saccharomyces cerevisiae
Scientic Supervisor / Contact Person
Name and Surname
Victor Jimenez Cid
ORCID (link)
Researcher ID (link)
Localization & Research Area
Faculty / Institute
Faculty of Pharmacy
Department
Microbiology and Parasitology
Research Area
Life Sciences (LIF)
MSCA & ERC experience
Research group / research team hosted any MSCA fellow?
No
Research group / research team have any ERC beneficiaries?
No
Research Team & Research Topic
Research Team / Research Group Name (if any)
920628 - Transducción de señales en Saccharomyces cerevisiae
Website of the Research team / Research Group / Department
Brief description of the Research Team / Research Group / Department
Our laboratory, located in the Department of Microbiology and Parasitology at the School of Pharmacy, is among the Universidad Complutense consolidated research groups (UCM-920628). Our interests are focused on the molecular mechanisms that govern cell signaling from sensors and receptors towards intracellular effector proteins in the yeast Saccharomyces cerevisiae, a eukaryotic model organism. Signaling pathways are essential for all cells, ranging from the most elementary prokaryotic systems to complex higher eukaryotes. They allow sensing and adapting to environmental conditions as well to cell-to-cell communication. Highly conserved through evolution, these pathways respond to diverse stimuli to rule physiological processes that are crucial for cell survival and the control of proliferation. Our group consists of five Senior Researchers, one postdoctoral and four predoctoral researchers, plus Master and Undergraduate Students. The Department is fully equipped for performing high standards research in Microbiology, Molecular and Cell Biology.
Our current expertise is focused on two main lines. The first line derives from more than two decades of dedication to the field under the lead of Prof. María Molina and Humberto Martín, which we started with the cloning and characterization of the MAPK (mitogen-activated protein kinase)-coding SLT2 gene, responsible for the maintenance of cell wall integrity (CWI) in the yeast cell. Along the years, we have studied the function of diverse constituents of this pathway, the mechanisms that control their activation and regulation, especially those related with phosphorylation/dephosphorylation events, as well as their interaction with other signaling pathways. The second line, led by Prof. Víctor J. Cid, Isabel rodríguez-Escudero and Teresa Fernández-Acero exploits this expertise for the development of humanized yeast models in order to study human signaling pathways related to human disease. We have reconstituted in yeast the oncogenic human PI3K pathway, studied bacterial virulence factors that interfere with cell signaling, and are currently applying synthetic biology techniques to assemble signalosomes related to innate immunity, such as the myddosome in TLR signaling, the inflammasome and the cGAS-STING pathway.
Our current expertise is focused on two main lines. The first line derives from more than two decades of dedication to the field under the lead of Prof. María Molina and Humberto Martín, which we started with the cloning and characterization of the MAPK (mitogen-activated protein kinase)-coding SLT2 gene, responsible for the maintenance of cell wall integrity (CWI) in the yeast cell. Along the years, we have studied the function of diverse constituents of this pathway, the mechanisms that control their activation and regulation, especially those related with phosphorylation/dephosphorylation events, as well as their interaction with other signaling pathways. The second line, led by Prof. Víctor J. Cid, Isabel rodríguez-Escudero and Teresa Fernández-Acero exploits this expertise for the development of humanized yeast models in order to study human signaling pathways related to human disease. We have reconstituted in yeast the oncogenic human PI3K pathway, studied bacterial virulence factors that interfere with cell signaling, and are currently applying synthetic biology techniques to assemble signalosomes related to innate immunity, such as the myddosome in TLR signaling, the inflammasome and the cGAS-STING pathway.
Research lines / projects proposed
We offer two lines: the first involves gaining insight into MAPK signaling and aims to understand the importance of the spatial architecture of the CWI pathway. By artificially relocating the MAPK Slt2 to specific subcellular compartments and functional complexes, we should be able to define the contribution of local substrates to outputs of this pathway, and discern its cytoplasmic functions from the transcriptional response linked to nuclear translocation of the kinase. This approach can also provide valuable information on how MAPK activation at different locations influences signal propagation and intensity. Additionally, by generating new affinities between the Slt2 MAPK and other components of the CWI pathway that are not direct Slt2-interactors, novel circuitries of the CWI network will be established, which can be also exploited to study in depth the configuration and regulatory mechanisms of MAPK pathways.
The second line involves Synthetic Biology strategies to assemble human signalosome-based complexes in the yeast cell. We will take advantages of signalosome adaptors FADD, ASC, MyD88, TIRAP and TRAM for cellular reprogramming. We will engineer chimeric protein modules that combine subcellular localization signals that target particular yeast cytoplasmic membrane organelles with protein-protein interaction modules (TIR, CARD or DD domains) of human origin, aiming to create artificial membrane junctions in the cell. The assembly of the modules will be controlled by conditional expression of the adaptor. This should allow, on one side, to gain knowledge on the functions of such organelle junctions and, on the other side, to devise screening platforms to search for molecules that target the human signalosome complexes, a useful tool in anti-inflammatory, immunomodulatory and antitumoral drug discovery.
The second line involves Synthetic Biology strategies to assemble human signalosome-based complexes in the yeast cell. We will take advantages of signalosome adaptors FADD, ASC, MyD88, TIRAP and TRAM for cellular reprogramming. We will engineer chimeric protein modules that combine subcellular localization signals that target particular yeast cytoplasmic membrane organelles with protein-protein interaction modules (TIR, CARD or DD domains) of human origin, aiming to create artificial membrane junctions in the cell. The assembly of the modules will be controlled by conditional expression of the adaptor. This should allow, on one side, to gain knowledge on the functions of such organelle junctions and, on the other side, to devise screening platforms to search for molecules that target the human signalosome complexes, a useful tool in anti-inflammatory, immunomodulatory and antitumoral drug discovery.
Key words
Application requirements
Professional Experience & Documents
We search for a motivated Postdoctoral fellow with experience in Cellular and Molecular Biology, ready to work in a friendly and social environment. We appreciate creative minds. Although not mandatory, we will value experience in Microbiology, yeast Genetics and tissue culture handling.
Please submit a letter of motivation and a short CV listing scientific achievements, professional career and publications. We may ask for an interview and/or two recommendation letters from former mentors.
Please submit a letter of motivation and a short CV listing scientific achievements, professional career and publications. We may ask for an interview and/or two recommendation letters from former mentors.
One Page Proposal
You can attach the 'One Page Proposal' to enhance the attractiveness of your application. Supervisors usually appreciate it. Please take into account your background and the information provided in Research Team & Research Topic section to fill in it.
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