Стратегії проповідницького дискурсу І. Галятовського: антропологічний аспект

How cells in developing organisms interpret the quantitative information contained in morphogen gradients is an open question. Here we address this question using a novel integrative approach that combines quantitative measurements of morphogen-induced gene expression at single-mRNA resolution with mathematical modelling of the induction process. We focus on the induction of Notch ligands by the LIN-3/EGF morphogen gradient during vulva induction in Caenorhabditis elegans. We show that LIN-3/EGF-induced Notch ligand expression is highly dynamic, exhibiting an abrupt transition from low to high expression. Similar transitions in Notch ligand expression are observed in two highly divergent wild C. elegans isolates. Mathematical modelling and experiments show that this transition is driven by a dynamic increase in the sensitivity of the induced cells to external LIN-3/EGF. Furthermore, this increase in sensitivity is independent of the presence of LIN-3/EGF. Our integrative approach might be useful to study induction by morphogen gradients in other systems

Snooping on cells in worms and mini-organs

Throughout their lifetime, animals face a wide variety of biological challenges. Starting out as single cells, their _rst challenge is to undergo development and become fully grown and functional adults. Remarkably, this incredibly complex process occurs in a highly reproducible manner despite the huge variability in environmental, genetic and molecular uctuations they encounter during their journey through development. However, the challenges do not end here; once animals become adults, their tissues are constantly subject to damage, either by external sources such as disease, or due to intrinsic causes such as cellular aging. Thus, adult tissues are constantly renewing themselves, and must do so in a tightly controlled manner in order to maintain homeostasis. In this thesis, we explore how animals cope with a few of such challenges with the help of two model systems, C. elegans worms and stem cell-derived organoids.BN/Sander Tans La

Long-term expanding human airway organoids for disease modeling

Organoids are self-organizing 3D structures grown from stem cells that recapitulate essential aspects of organ structure and function. Here, we describe a method to establish long-term-expanding human airway organoids from broncho-alveolar resections or lavage material. The pseudostratified airway organoids consist of basal cells, functional multi-ciliated cells, mucus-producing secretory cells, and CC10-secreting club cells. Airway organoids derived from cystic fibrosis (CF) patients allow assessment of CFTR function in an organoid swelling assay. Organoids established from lung cancer resections and metastasis biopsies retain tumor histopathology as well as cancer gene mutations and are amenable to drug screening. Respiratory syncytial virus (RSV) infection recapitulates central disease features, dramatically increases organoid cell motility via the non-structural viral NS2 protein, and preferentially recruits neutrophils upon co-culturing. We conclude that human airway organoids represent versatile models for the in vitro study of hereditary, malignant, and infectious pulmonary disease