Functional Genomics of Cell Morphogenesis
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.
- Vaggi F, Schiavinotto T, Lawson JL, Chessel A, Dodgson J, Geymonat M, Sato M, Carazo-Salas RE#, Csikász-Nagy A. A scientific approach to interdisciplinary conference organization. Invited Feature Article. eLife 2014;3:e02273. DOI: 10.7554/eLife.02273
- Lawson JL, Carazo-Salas RE#. Microtubules: greater than the sum of the parts. Biochem Soc Trans. 2013 Dec 1;41(6):1736-44. doi: 10.1042/BST20130239
- Bajpai A, Feoktistova A, Chen JS, McCollum D, Sato M, Carazo-Salas RE, Gould KL, Csikász-Nagy A. Dynamics of SIN asymmetry establishment. PLoS Comput Biol. 2013 Jul;9(7):e1003147
- Carazo-Salas R E, Czikasz-Nagy A and Sato M (2013) Cellular polarity : From mechanisms to disease. Philosophical Transactions of the Royal Society B : Special issue. Publication Online 23 Sept 2013, paper November 2013 > > See contents > Read papers
- Dodgson J, Chessel A, Yamamoto M, Vaggi F, Cox S, Rosten E, Albrecht D, Geymonat M, Csikàsz-Nagy A, Sato M and Carazo-Salas R E (2013) Spatial segregation of polairty factors into distinct cortical clusters is required for cell polarity control. Nature Communications. 2013;4:1834
- Vaggi F, Dodgson J, Bajpai A, Chessel A, Jordán F, Sato M, Carazo-Salas R E 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 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 R E and Nurse P (2007) Self-Organization of interphase microtubule arrays in fission yeast. Nature Cell Biology 3:95-6.
- Carazo-Salas R E, Antony C and Nurse P (2005) The kinesin Klp2 mediates polarization of interphase microtubules in fission yeast. Science 309(5732):297-300