We study how eukaryotic cells measure their own growth, and how ceramides, nutrients and lipid signals link that measurement to the cell cycle in yeast.
Cells only move to the next stage of the cycle once they have grown enough. So they must be able to measure their own growth.
Regulation of cell growth is crucial for the survival, development and adaptation of all organisms. In every cell, key transitions in the cell cycle occur only after a certain threshold of growth has been reached, so that enough growth happens during each phase of the cycle.
To do this, cells must translate growth-related events into a proportional signal that reflects how much they have grown. How eukaryotic cells sense growth and coordinate it with cell cycle progression has remained deeply puzzling.
Our work has shown that lipid metabolism, and ceramides in particular, play a central role in coordinating cell growth with cell division in both fission and budding yeast, together with a conserved TORC2 signalling network that responds to nutrients.
Our data suggest a connection between ceramide production and the signalling pathways that control cell wall synthesis, cell division and fungal pathogenesis.
The findings could open new ways to design therapies that target ceramide-regulated pathways in resistant pathogenic fungi.
A rod-shaped cell that grows at its tips and divides in the middle at a constant size.
A plant pathogen that switches from budding yeast to an infective filament. We use it to ask whether ceramide-dependent morphogenesis is conserved in a pathogenic fungus.
Infective filament (DIC). Image: Flor-Parra, Castillo-Lluva and Pérez-Martín, The Plant Cell 2007
Ceramide synthases keep the fungal plasma membrane intact and working, and shape cell wall synthesis, growth and division. We want to find the molecular mechanisms that link ceramide biosynthesis to these processes.
Two genome-wide genetic screens look for processes that compensate for the loss of ceramide synthase activity. We then test key candidates related to growth-dependent signalling pathways.
We are building a global analysis of lipids in fission yeast. Cells tightly control their lipid composition and distribution to support membrane function and signalling.
Nutrient signals reshape the architecture of the plasma membrane. We study how eisosome remodelling and TORC2 signalling adjust cell growth when nutrients change.
We will use Ustilago maydis, a well-established model for studying fungal dimorphism and virulence, to investigate whether ceramide synthases contribute to the developmental transitions required for infection. This exploratory approach will provide an initial assessment of the evolutionary conservation of ceramide-dependent morphogenesis in a pathogenic context, while opening the possibility of identifying shared principles underlying fungal development and virulence.
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Anita's first-author preprint is out on bioRxiv. We show that Lac1-dependent ceramide synthesis couples septum assembly to cell separation in fission yeast: without it, septum-synthesis enzymes linger at the division site and most cells die as they try to separate.
Read the preprint →Our work on how specific defects in ceramide structure uncouple nutrient sensing from cell size control is out. It grew from Nacho's TFG and TFM. Great work!
Read the paper →María is now Associate Professor in the Department of Cell Biology at the University of Seville.
When funding is tight, or there is none at all, we celebrate this work as if we were climbing Everest.
Read the preprint →Ana María will do her PhD in the lab after ranking #17 among all candidates in Spain.
Published together with a First Person interview with Rafa.
Read the paper →The two Isas join us in their third year of Biology to learn PCRs, western blots and yeast experiments.
Eu starts a Master's in Education, Andrea a Master's in Health Biotechnology, Marta is looking for a job after her Master's, and Pilar is about to start work at a hospital. We will miss you all.
Dragos-Aurelian Vasvari, an Erasmus student from Constructor University (Germany), joins us for eight weeks to learn fission and budding yeast techniques.
Through a collaboration between María Alcaide's lab and a Higher Education Institute in Pathology, Pilar Valera joins us for six weeks as a technician.
After three years at the University of Seville, Rafa is now Associate Professor.
Eu receives a University fellowship to work in the lab for a few months.
Our preliminary work on Yck1/2 kinases regulating the TORC2 pathway is out on bioRxiv.
Read the preprint →Nacho's first meeting: he presented his work at the XX Meeting of the Spanish Society of Cell Biology.
Anita obtains a «Beca de Colaboración» from the Spanish Ministry of Education to work on TORC2 signalling and nutrients.
Impact of sphingolipids on protein membrane trafficking, in BBA – Molecular and Cell Biology of Lipids.
Read the paper →Nacho presents his work at the XIX IBIS Researchers Forum 2023.
With a grant from the Junta de Andalucía, María starts her group on eisosomes and cell growth and size control.
Rafa presents at the 13th Red Nacional de Levaduras.
Our first paper from the lab is named best paper of January 2022 at the School of Biology.
Three new members join the lab to learn how to treat yeasts.
Rafa presents Nacho's work on cell growth control at the 44th SEBBM meeting, and wins the prize for fastest «pipeteador».
Rafa and Nacho spend the summer at UC Santa Cruz and at IBBTEC in Cantabria.
Associate Professor (Profesor Titular) of Cell Biology, University of Seville
Associate Professor (Profesora Titular) of Cell Biology, University of Seville
B.S. Biology, University of Seville · M.Sc. Molecular Genetics and Biotechnology
Collaborator on fission yeast cell biology and ceramide-dependent growth signals.
Studies how cells sense the behaviour of lipids and how this controls cellular functions.
Former members: Isabel Castaño (Undergraduate) · Isabel Silva (Undergraduate) · Nacho Quesada-Márquez (Master's) · Eugenia Cabezas Olmo (Undergraduate) · Andrea del Valle Zapata (Undergraduate)
We are excited about new members at every stage, from undergraduates to postdocs. If funding is not available yet, write to us anyway and we can discuss options together.