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Biology subjects

Wischik, I.

Publications and source records attributed to Wischik, I..

2 recordsLinked to original sources

From Flocks to Swarms: Rewriting the Rules of Collective Cell Migration

From flocking birds to swarming insects, collective motion enables groups to accomplish tasks beyond the capabilities of individuals. These behaviors emerge from local interactions among group members, but the interaction rules that organize collectives at the cellular scale remain poorly understood, in part because they are difficult to manipulate experimentally. Here we develop a cell-machine interface that enables us to rewrite the rules of collective migration. Cell-cell interaction rules are specified in software and implemented in living cells through real-time computer vision and closed-loop optogenetic control. Using a single engineered cell line, we program cells to self-organize into flocks, to propagate regenerative signal relays that recapitulate the interaction logic of immune-cell swarms, and to collectively navigate guidance cues that individual cells cannot. Our work shows that altering simple rules of cell-cell interaction is sufficient to generate new emergent collective capabilities. This approach provides an experimental framework for discovering the organizational principles of multicellular coordination and designing synthetic collectives with capabilities beyond those of their individual members.

synthetic biology↗

Atypical PI3Ks coordinate chemotaxis, signaling dynamics, and multicellular development in Dictyostelium

Phosphoinositide 3-kinase (PI3K) signaling regulates protrusion, polarity, membrane uptake, and multicellular development in Dictyostelium discoideum, but these functions have been interpreted largely through canonical Class I PI3Ks and PI(3,4,5)P production. This framework does not fully explain how PI3K-dependent pathways attenuate Ras activity, organize PI(3,4)P2-associated polarity states, support cAMP relay, or coordinate development. Here, we identify three atypical PI3K-family enzymes--PikF, PikG, and PikH--as functionally distinct regulators of these processes. PikF constrains Ras-phosphoinositide-actin signaling; pikF- cells show prolonged cAMP-stimulated Ras activation, extended PIP recruitment, delayed PI(3,4)P2 biosensor recovery, elevated peripheral actin activity, impaired chemotactic precision, and delayed abnormal development. PikG acts through a distinct relay-associated pathway: pikG- cells fail to generate endogenous cAMP oscillations, display disrupted ACA polarity, deposit spatially disorganized ACA-positive vesicle trails, and fail to aggregate. PikH, in contrast, supports efficient phagocytic uptake with little effect on acute chemotactic signaling. Kinase-dead rescue experiments show that conserved catalytic lysines are required for PikF- and PikG-dependent development and PikH-dependent uptake. Together, our results reveal that atypical PI3Ks diversify the Dictyostelium PI3K signaling toolkit, separating protrusive signal attenuation, cAMP relay organization, membrane uptake, and multicellular development into distinct kinase-dependent modules.

cell biology↗