Mechanics in development
How cells collectively leverage
mechanical asymmetries and feedback to drive
developmental processes robustly remains poorly
understood. One critical developmental process is
neurulation: the formation of the neural tube, which
later develops into the central nervous system. Together
with the Mangan group
and the Munro
lab, I am using data-driven modeling to
investigate the mechanochemical feedbacks which drive
neural tube closure.
Vertebrate ectodermal appendages
(teeth, hair follicles, scales, feathers, mammary
glands) all originate from interactions between two
adjacent tissue layers: the epithelium and mesenchyme.
One of the first fundamental bifurcations during
ectodermal appendage organogenesis relates to the
physical bending of epithelial sheets, leading either to
invagination or evagination. The mechanisms that
determine epithelial bending direction remain poorly
understood. I collaborate with the Sam Norris in the Shubin Lab
to combine biophysical modeling with in vivo
experiments in catsharks to determine the key mechanisms
which dictate these divergent bending modes.
Bacterial
aggregates: formation and microarchitecture
The bioluminescent bacterium, Vibrio
fischeri, is the exclusive symbiont of the light
organ of bobtail squids. In order to colonize the light
organ of new squid generations, V. fischeri must
form transient aggregates in a mucus-rich ciliated zone
on the outer surface of the light organ. I collaborate
with the Nirody
Lab to investigate how the microenvironment
mechanics impact and potentially drive bacterial
aggregation.
Understanding how microarchitecture of
biofilms impacts resource distribution can serve to
inform mechanisms of addressing antibiotic resistance. I collaborate with the Nirody Lab
to investigate, using an inverse problems perspective,
how metabolic activity of P. aeruginosa biofilms
depends on their underlying microarchitecture.
Actin network dynamics
The actin cytoskeleton—complex
self-organized assemblies of actin protein filaments and
auxiliary proteins—plays important roles in cell shape
and mechanics through the dynamics of self-organized
higher-order architectures such as networks. Through
molecular-scale interactions with molecular motors,
global cell-scale contractile behaviors emerge,
harnessed for cellular processes such as cell
organization, motility, and intracellular transport.
Mathematical modeling in conjunction with in vitro
reconstitutions can reveal the relative importance of
active stresses, friction, cell geometry, and turnover
in directing actin network dynamics. My collaborators on
such work have included Alex Mogilner,
Charles S.
Peskin, Kinneret
Keren, and the Cytomorpho Lab
of Profs. Laurent Blanchoin and Manuel Théry.
Collective cell migration
Collective cell migration plays key
roles in processes such as embryonic development and
cancer metastasis. The ability of cell clusters to
collectively migrate in a directional manner requires
cues such as signaling in development. However,
how cells in cancer clusters coordinate their movements
is still not well understood. Toward this aim, I have
worked with the Carmofon Lab to
reveal how mechanics of the ECM can drive the directed
migration of tumor cell clusters.
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