We study how embryos integrate biochemical signaling, cytoskeletal dynamics and cell mechanics to orchestrate complex cell and tissue behaviors. We combine live imaging, genetic perturbations, biophysical analysis, and computer simulations to address questions in three main areas: Dynamic control of self-organized actomyosin contractility, cell polarization in C. elegans, and tissue morphogenesis in aascidians
The forces that shape embryonic cells and tissues are produced by dynamic contractile networks of actin filaments, myosin motors and cross-linking proteins. The big challenge is to understand how embryonic cells remodel these networks by tuning network assembly, architecture and motor activity to do a sequence of different jobs – to polarize, move, change shape and divide. To address this challenge, we combine in vivo studies in C. elegans with computer simulations, focusing on three specific examples: the long range flows that polarize cells, self assembly of the contractile ring during cytokinesis, and dynamic control of pulsatile contractions that coordinate cell shape change and rearrangements during morphogenesis.
We also use C. elegans embryos as a model system to explore how cells form and stabilize polarity in response to transient polarizing cues. In recent years, we (and others) have uncovered a network of biochemical and mechanical interactions involving conserved PAR polarity proteins, small Rho family GTPases, and the acvtomyosin cytoskeleton, that do this job. We combine single molecule imaging, genetic manipulations and biophysical analysis to characterize key elements of this “mechanochemical circuit”, and to probe the fundamental design principles that allow this circuit to do it's job in such an extraordinarily robust way.
Finally, we use ascidians (“sea squirts”) as a simple model system to study how embryos organize force production in space and time to shape tissues and organs. Ascidians make the many of the same structures that we do - e.g. a notochord, a simple gut and a neural tube, but they do so with very few (tens of) cells, in small optically clear embryos, that are highly accessible to genetic, pharmacological and physical manipulations. We currently focus on neural tube closure. Combining experiments with computer simulations, we ask how embryos use tissue-specific gene expression and conserved pathways for planar and apico-basal polarity to pattern actomyosin contractility in space and time to shape and close the neural tube.
Fred Hutchison Cancer Research Center
Seattle, Wa
Postdoctoral fellow - Cell Biology
2002
University of Washington
Seattle, WA
PhD - Cell and Developmental Biology
2000
Hampshire College
Amherst, MA
BA - Mathematics and Biology
1987
Oligomerization of peripheral membrane proteins provides tunable control of cell surface polarity.
Oligomerization of peripheral membrane proteins provides tunable control of cell surface polarity. Biophys J. 2022 12 06; 121(23):4543-4559.
PMID: 36815706
Fat2 polarizes the WAVE complex in trans to align cell protrusions for collective migration.
Fat2 polarizes the WAVE complex in trans to align cell protrusions for collective migration. Elife. 2022 09 26; 11.
PMID: 36154691
Pulsatile contractions and pattern formation in excitable actomyosin cortex.
Pulsatile contractions and pattern formation in excitable actomyosin cortex. PLoS Comput Biol. 2022 03; 18(3):e1009981.
PMID: 35353813
Modulating RhoA effectors induces transitions to oscillatory and more wavelike RhoA dynamics in Caenorhabditis elegans zygotes.
Modulating RhoA effectors induces transitions to oscillatory and more wavelike RhoA dynamics in Caenorhabditis elegans zygotes. Mol Biol Cell. 2022 05 15; 33(6):ar58.
PMID: 35138935
Filament-guided filament assembly provides structural memory of filament alignment during cytokinesis.
Filament-guided filament assembly provides structural memory of filament alignment during cytokinesis. Dev Cell. 2021 09 13; 56(17):2486-2500.e6.
PMID: 34480876
Roadmap for the multiscale coupling of biochemical and mechanical signals during development.
Roadmap for the multiscale coupling of biochemical and mechanical signals during development. Phys Biol. 2021 04 14; 18(4).
PMID: 33276350
Actin bundle architecture and mechanics regulate myosin II force generation.
Actin bundle architecture and mechanics regulate myosin II force generation. Biophys J. 2021 05 18; 120(10):1957-1970.
PMID: 33798565
Roadmap on multiscale coupling of biochemical and mechanical signals during development.
Lenne PF, Munro E, Heemskerk I, Warmflash A, Bocanegra-Moreno L, Kishi K, Kicheva A, Long Y, Fruleux A, Boudaoud A, Saunders TE, Caldarelli P, Michaut A, Gros J, Maroudas-Sacks Y, Keren K, Hannezo E, Gartner ZJ, Stormo BS, Gladfelter AG, Rodrigues A, Shyer A, Minc N, Maître JL, Di Talia S, Khamaisi B, Sprinzak D, Tlili S. Roadmap on multiscale coupling of biochemical and mechanical signals during development. Phys Biol. 2020 Dec 04.
PMID: 33276350
Apical Relaxation during Mitotic Rounding Promotes Tension-Oriented Cell Division.
Apical Relaxation during Mitotic Rounding Promotes Tension-Oriented Cell Division. Dev Cell. 2020 12 21; 55(6):695-706.e4.
PMID: 33207225
The Dynamics of P Granule Liquid Droplets Are Regulated by the Caenorhabditis elegans Germline RNA Helicase GLH-1 via Its ATP Hydrolysis Cycle.
The Dynamics of P Granule Liquid Droplets Are Regulated by the Caenorhabditis elegans Germline RNA Helicase GLH-1 via Its ATP Hydrolysis Cycle. Genetics. 2020 Jun 01; 215(2):421-434.
PMID: 33954500