Research at Molecular Cytology

Molecular Cytology is the study of the dynamic architecture of living cells. Our central theme is 'Self-organization and signaling in living cells'. Self-organization is the intrinsic property of matter to organize itself in a (dynamic) structure, whereas signaling implies the activity of gene-products to control a local activity which can alter the local cellular architecture (e.g. driving morphogenesis). In order to achieve a certain 3D architecture in cells, these two important mechanisms work in concert. At Molecular Cytology both mechanisms are studied with emphasis on membrane-related architecture of living cells using advanced microscopy tools.
 

The two main research areas are:

Spatial organisation of sub-cellular signalling - group leaders: prof. dr. T.W.J. Gadella, dr. ir. J. Goedhart, dr. ir. M.A. Hink

By employing genetic encoded fluorescent biosensors we analyze the in situ molecular interactions between signaling molecules (phospholipid-second messengers, receptors, G-proteins and effector molecules) & flow of information across and in the plane of the membrane of living mammalian cells. We aim to understand how cells can achieve and maintain a local signal in the membrane (e.g. in order to drive morphogenesis, or to define new cytoskeletal anchorage or vesicle-docking sites).

Molecular dynamics of the bacterial cell cycle - group leader: dr. T. den Blaauwen

The morphology of rod shaped bacteria is achieved through two very dynamic synthetic complexes: the elongasome and the divisome. The elongasomes use the actin-like cytoskeleton MreB helix underneath the plasma membrane as tracking devise to elongate the cell envelope whereas the divisome is responsible for division and the synthesis of new cell poles. Cell division is directed by the FtsZ ring (a tubulin homolog) that exerts a small force on the bacterial envelope. The assembly and the dynamics of the elongasome and divisome are studied in vivo using immunofluorescence and fluorescence microscopy techniques (FRET, FRAP, localization) and in vitro using state of the art biochemical and biophysical techniques. By aiming to obtain quantitative data, we hope to model the measured and observed interactions.

Computational modelling of Cnidarian embryogenesis - group leader: dr. M. Postma

Embryonic development inherently is a complex interplay between gene regulation, morphological changes of cells and tissue, and environmental conditions. In recent time significant progress has been made in identifying transcription factors and signalling pathways that regulate embryogenesis. Additionally, detailed time dependent morphological data on cells and embryo's are becoming available. One of the major challenges in developmental biology is to integrate all the data into spatiotemporal computational models that realistically describe the dynamics of embryogenesis.

As a primary model organism Nematostella vectensis is used. This projects aims to design, test and investigate computational models of embryogenesis, primarily driven by experimental data. We aim to reconstruct the gene regulatory networks that determine body-plan formation during several early developmental stages. Furthermore, we want to get a better understanding on how genes interact with biomechanics, by developing three-dimensional mechanical models of embryogenesis. These models will be validated by using fluorescent probes and advanced fluorescent microscopy techniques to follow cell and tissue dynamics in living embryos. Using these models we will investigate how multiple mechanisms involved in shaping the embryo may lead to robust embryogenesis. By comparing Nematostella vectensis embryogenesis to related organisms the models can give insights into evolutionary aspects of embryogenesis. General applicable techniques will be developed for analyzing experimental data, multi-scale modelling of tissue and cell mechanics, modelling of genetic regulation and signalling, parameter estimation and model analysis.

Advanced light microscopy

The above research lines are strongly supported by the development and implementation of advanced light microscopy, since it enables a sensitive, non-invasive and highly specific way of visualizing structures and interactions in cells (prof. dr. G.J. Brakenhoff, prof. dr. T.W.J. Gadella, prof. dr. E.M.M. Manders & dr. M.A. Hink).