{"id":10,"date":"2023-03-20T14:39:20","date_gmt":"2023-03-20T14:39:20","guid":{"rendered":"https:\/\/geiselmed.dartmouth.edu\/landino\/?page_id=10"},"modified":"2026-10-30T20:46:10","modified_gmt":"2026-10-30T20:46:10","slug":"research","status":"publish","type":"page","link":"https:\/\/geiselmed.dartmouth.edu\/landino\/research\/","title":{"rendered":"Research"},"content":{"rendered":"

Cellular Self-Organization and Cell Divison<\/strong><\/h3>\n
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Four panels from time lapse imaging of self-organized Rho (cyan) and filamentous actin (F-actin, magenta) waves traveling across a supported lipid bilayer. Active Rho leads the wave front and is followed in space and time by F-actin.<\/figcaption><\/figure>\n

The Landino Lab is interested in understanding how cells organize and remodel their cellular architecture to carry out essential cellular functions. One lens through which we study this is cytokinesis, the process by which one cell divides its genetic and cellular material into two new daughter cells. Cytokinesis is a highly choreographed, dynamic event that requires coordination between signaling pathways and remodeling of structural networks. Cell division is an essential process for all life, and errors in cell division are correlated with disease states like cancer. We aim to determine the foundational principles that underlie cellular organization and cell division to better understand how these processes are disrupted during disease.<\/p>\n

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Cortical Patterning<\/h3>\n

Recent studies have shown that the cell cortex is dynamically patterned during c<\/p>\n

ell division. The cell cortex is a thin network of F-actin that supports the plasma membrane and defines the structure and function of animal cells. Cortical F-actin is rapidly assembled and disassembled in wave-like patterns that emerge during cell division in early embryos. This self-organized patterning emerges through coupled positive and negative feedback signaling mediated by the small GTPase Rho. Our lab uses cell-free reconstitution to assemble cell cortices in vitro and investigate the biochemical and biophysical mechanisms that regulate these patterns. Our long-term goal is to determine how dynamic cortical patterning promotes successful cell division.<\/p>\n

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Approach<\/h3>\n

The Landino Lab uses African clawed frogs (Xenopus<\/em> laevis<\/em>) as a model to investigate protein signaling pathways that are relevant for understanding human disease. Xenopus<\/em> are an ideal model system to carry out biochemical reconstitution of cellular phenomena, as the proteins and signaling mechanisms are well conserved with humans. Frogs can be induced to lay eggs on demand, and Xenopus<\/em> lay hundreds of eggs in a single clutch. The eggs are 1 mm in diameter, and we can easily obtain bulk, undiluted cytoplasm by centrifugation. Eggs are cell cycle arrested, allowing us to chemically control the cell cycle state of the cytoplasm.<\/p>\n

We previously developed and characterized an artificial cortex system to investigate mechanisms of cortical patterning in vitro<\/em>. The artificial cortex is comprised of supported lipid bilayers (SLBs) and cytoplasm from Xenopus<\/em> eggs (egg extract). This combination is sufficient to produce multiple regimes of cortical patterning (Landino et al. 2021<\/a>) and reconstitute dynamics comparable to those describes in vivo<\/em>. This powerful, biochemical system allows us to carefully manipulate and examine features of the cortex that are not easily perturbed in cells or in whole embryos.<\/p>\n

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Our lab using quantitative, live imaging by TIRF (Total Internal Reflection Fluorescence) microscopy to track cortical pattern dynamics over time. We use recombinant biosensors to measure both bulk and dynamic activity in the artificial cortex. Cortical pattern dynamics are quantified by custom code (waveanalysis<\/em>) which enables high throughput, unbiased temporal image analysis.<\/p>\n

Ongoing Projects<\/h3>\n

Role of membrane composition in cortical patterning<\/h4>\n

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The relationship between the cell\u2019s plasma membrane and the actin cortex is important for building a variety of cytoskeletal networks and for determining cell structure. Our lab recently discovered that plasma membrane composition regulates cortical patterning dynamics and pattern regime (Schwarz et al. MBoC<\/a>). This work was recognized by the MBoC editorial board for its novelty and impact with the 2026 MBoC Paper of the Year Award<\/a>.<\/p>\n

We continue to investigate the relationship between membrane composition and cortical actin. Ongoing projects are focused on the role of phosphatidylinositol signaling, actin anisotropy, and membrane curvature.<\/p>\n

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Rho family GTPase crosstalk<\/h4>\n

Current models indicate that Rho-mediated positive feedback, through the RhoGEF Ect2, and negative feedback via<\/em> F-actin are necessary for cortical patterns to develop. We are currently exploring the role of other Rho-family GTPases in modulating the cortical excitability circuit. Additionally, we are testing how these GTPases are spatially organized in response to spatial makers of cytokinesis, such as microtubule asters.<\/p>\n

Cortical patterning in cell division and development<\/h4>\n

Cortical patterns emerge during early embryogenesis, a stage of life with many rapid, synchronous cell divisions. Pattern dynamics are coupled to both cell cycle state and developmental stage in Xenopus<\/em> embryos. We are currently investigating the molecular mechanisms that regulate cortical patterns in these physiological states. Ongoing projects include investigating cortical waves in single cells, testing the role of cell cycle state, and investigating the relationship between cortical waves and cell surface area.<\/p>\n","protected":false},"excerpt":{"rendered":"

Cellular Self-Organization and Cell Divison The Landino Lab is interested in understanding how cells organize and remodel their cellular architecture to carry out essential cellular functions. One lens through which we study this is cytokinesis, the process by which one cell divides its genetic and cellular material into two new [\u2026] <\/p>\n

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