Cytoskeletal Dynamics
ABOUT
Our research focuses on understanding how actomyosin dynamics generate contractile forces in vivo. We investigate how actin filaments, non-muscle myosin II motors, crosslinkers, and nucleators are organized and tuned to build functional networks that drive cell division, tissue morphogenesis, and other contractility-dependent processes.
RESEARCH
Our research aims to decode how actin filament networks are assembled, organized, and tuned to generate contractility in living organisms. We focus on cytokinesis, the final step of cell division, when an actomyosin contractile ring assembles and constricts to physically separate daughter cells. Using the nematode C. elegans, which offers powerful genetics, genome engineering, and great accessibility for high-resolution live imaging, we dissect how actin crosslinkers, nucleators, and myosin motors regulate network architecture, force generation, and constriction robustness. Our work has uncovered mechanisms that preserve the integrity of the contractile ring and ensure reliable cytokinesis completion.
We are now extending this work to understand how actin regulators generate specialized contractile networks across tissues during morphogenesis and organ function. We investigate how network architecture is tuned to support contractions in the myoepithelial spermatheca, cell invasion and remodeling in the vulva, and contractility in skeletal muscle. These contexts require distinct structural and mechanical properties. Because actin regulators and contractility pathways are highly conserved and frequently altered in cancer and other diseases, our research provides fundamental mechanistic insight into how cytoskeletal organization governs cell and tissue function.
Selected Publications
Plastin and spectrin cooperate to stabilize the actomyosin cortex during cytokinesis. Current Biology31(24):5415-5428.e10, 2021. [Journal: Article] [CI: 13] [IF: 10,9]
DOI: 10.1016/j.cub.2021.09.055 SCOPUS: 85121234178
Leite J., Chan F.Y., Osório D.S., Saramago J., Sobral A.F., Silva A.M., Gassmann R., Carvalho A.X.
Equatorial Non-muscle Myosin II and Plastin Cooperate to Align and Compact F-actin Bundles in the Cytokinetic Ring. Frontiers in Cell and Developmental Biology8:, 2020. [Journal: Article] [CI: 13] [IF: 6,7]
DOI: 10.3389/fcell.2020.573393 SCOPUS: 85092498962
Osório D.S., Chan F.Y., Saramago J., Leite J., Silva A.M., Sobral A.F., Gassmann R., Carvalho A.X.
Crosslinking activity of non-muscle myosin II is not sufficient for embryonic cytokinesis in C. elegans. Development146(21):, 2019. [Journal: Article] [CI: 23] [IF: 5,6]
DOI: 10.1242/dev.179150 SCOPUS: 85074964249
Leite J., Osorio D.S., Sobral A.F., Silva A.M., Carvalho A.X.
Network contractility during cytokinesis—from molecular to global views. Biomolecules9(5):, 2019. [Journal: Article] [CI: 21] [IF: 4,1]
DOI: 10.3390/biom9050194 SCOPUS: 85066454203
Chan F.Y., Silva A.M., Saramago J., Pereira-Sousa J., Brighton H.E., Pereira M., Oegema K., Gassmann R., Carvalho A.X.
The ARP2/3 complex prevents excessive formin activity during cytokinesis. Molecular Biology of the Cell30(1):96-107, 2019. [Journal: Article] [CI: 34] [IF: 3,8]
DOI: 10.1091/mbc.E18-07-0471 SCOPUS: 85059257752
Mangal S., Sacher J., Kim T., Osório D.S., Motegi F., Carvalho A.X., Oegema K., Zanin E.
TPXL-1 activates Aurora A to clear contractile ring components from the polar cortex during cytokinesis. Journal of Cell Biology217(3):837-848, 2018. [Journal: Article] [CI: 48] [IF: 8,9]
DOI: 10.1083/jcb.201706021 SCOPUS: 85042867550
Silva A.M., Osório D.S., Pereira A.J., Maiato H., Pinto I.M., Rubinstein B., Gassmann R., Telley I.A., Carvalho A.X.
Robust gap repair in the contractile ring ensures timely completion of cytokinesis. Journal of Cell Biology215(6):789-799, 2016. [Journal: Article] [CI: 23] [IF: 8]
DOI: 10.1083/jcb.201605080 SCOPUS: 85009223214
Davies T., Jordan S.N., Chand V., Sees J.A., Laband K., Carvalho A.X., Shirasu-Hiza M., Kovar D.R., Dumont J., Canman J.C.
High-Resolution Temporal Analysis Reveals a Functional Timeline for the Molecular Regulation of Cytokinesis. Developmental Cell30(2):209-223, 2014. [Journal: Article] [CI: 61] [IF: 9,7]
DOI: 10.1016/j.devcel.2014.05.009 SCOPUS: 84904886021
Lewellyn L., Carvalho A., Desai A., Maddox A.S., Oegema K.
The chromosomal passenger complex and centralspindlin independently contribute to contractile ring assembly. Journal of Cell Biology193(1):155-169, 2011. [Journal: Article] [CI: 55] [IF: 10,3]
DOI: 10.1083/jcb.201008138 SCOPUS: 79955513613
Carvalho A., Desai A., Oegema K.
Structural Memory in the Contractile Ring Makes the Duration of Cytokinesis Independent of Cell Size. Cell137(5):926-937, 2009. [Journal: Article] [CI: 171] [IF: 31,2]
DOI: 10.1016/j.cell.2009.03.021 SCOPUS: 65849336045
