Rafael Carazo Salas PhD
Rafael is an ERC Starting Independent Researcher and a member of the Department of Genetics
Functional genomics of cell morphogenesis
Co-workers: Juan Francisco Abenza Martinez • Bálint Antal • Anatole Chessel • James Dodgson • Marco Geymonat • Joe Harvey • Jonathan Lawson • Yung-Chin Oei • Kathy Oswald
Plain English: An extraordinary capacity of cells is the ability to adopt specialized shapes and growth modes according to the functions they need to perform. For example, neurons adopt defined growth patterns in order to properly innervate our bodies, epithelial cells become polarized to correctly function in our skin and tissues, and blood cells take a specific shape allowing them to flow uninterrupted in our bloodstream. Not surprisingly, when cells lose control over that capacity they begin to malfunction and this leads to many human pathologies, ranging from neuronal disorders to cancer. Our general aim is to identify the networks of genes and proteins that regulate polarity, shape and growth pattern in cells, and to understand how the networks act in a coordinated manner to regulate those processes or become uncoordinated in disease.
An extraordinary capacity of cells is their ability to modulate their shape, polarity and intracellular cytoskeletal organisation, according to the functions they need to perform. Work in our lab seeks to elucidate how the gene and protein networks that regulate cellular growth, division and morphogenesis operate in space and in time, and how different cell shapes and growth patterns can arise from a single genome.
We have pioneered the development of 3D image-based high-throughput/high-content microscopy pipelines for yeast-based functional genomics studies. Using that approach, we recently completed the first comprehensive live cell-based screen for microtubule and cell shape regulators and discovered tens of novel candidate regulators - mostly evolutionarily conserved through to humans - which we are validating. Our aim is to generate the most exhaustive genomic map and phenotypic annotation of such regulators, and identify candidate biomedically-relevant targets. Capitalising on this technology, several other microscopy-based functional genomics projects are ongoing in our group.
We also recently discovered that the molecular machinery that regulates cell polarity localises to nanoscopic protein clusters at the cell cortex, with different regulators belonging to different cluster populations. This allows cells to control whether certain polarity regulators interact with others on the cortex, at different points of the cell cycle, revealing a fundamental hitherto ignored layer of cell polarity regulation.
Lastly, a large focus of the lab has shifted to establishing refined biophysical and micro-fabrication technologies to investigate how mechanical inputs modulate cell growth, a fundamental yet very poorly understood aspect of morphogenetic control.
• Dodgson J, Chessel A, Yamamoto M, Vaggi F, Cox S, Rosten E, Albrecht D, Geymonat M, Csikŕsz-Nagy A, Sato M and Carazo-Salas RE (2013) Spatial segregation of polairty factors into distinct cortical clusters is required for cell polarity control. Nature Communications. [In press]
• Vaggi F, Dodgson J, Bajpai A, Chessel A, Jordán F, Sato M, Carazo-Salas RE and Csikàsz-Nagy A (2012) Linkers of cell polarity and cell cycle regulation in the fission yeast protein interaction network. PLoS Computational Biology 8(10):e1002732. doi: 10.1371/journal.pcbi.1002732.
• Chessel, A, Dodgson, J and Carazo-Salas, R. E. (2012) Spherical spatial statistics for 3D fluorescence video-microscopy. 9th IEEE International Symposium on Biomedical Imaging (ISBI) 1747-50
• Carazo-Salas RE and Nurse P (2007) Self-Organization of interphase microtubule arrays in fission yeast. Nature Cell Biology 3:95-6.
• Carazo-Salas RE, Antony C and Nurse P (2005) The kinesin Klp2 mediates polarization of interphase microtubules in fission yeast. Science 309(5732):297-300