Danuser Lab

Danuser Lab - UT Southwestern

Objectives until April 2013:

• Integrate generic particle tracking software into OMERO
• Implement wizard to guide user through application-specific software controls

The Danuser lab studies the integration of chemical signals and mechanical forces in the regulation of cytoskeleton dynamics during cell migration, cell division and vesicle trafficking. They use live cell imaging approaches to visualise the molecular events underlying these processes in situ. Central to these imaging efforts is the development of cutting edge mathematical algorithms for the measurement of a wide range of image parameters to inform quantitative mechanistic models. Key technologies the lab has developed include quantitative Fluorescent Speckle Microscopy for the analysis of the structural dynamics of cytoskeleton components and macromolecular assemblies [1], models of cytoskeleton mechanics to derive from live cell measurements of cytoskeleton deformation intracellular force fields [2], single particle and single molecule tracking methods [3] to follow receptor dynamics [4] and vesicle trafficking [5]. More recently the lab’s mathematical focus has been on linear and non-linear correlation methods to identify from the constitutive fluctuations of molecular activities as visualised by live cell microscopy the spatial and temporal organisation of information flows in mechanochemical pathways [6].

Critical to all these applications is a complete and unbiased measurement of all image events visualised by a specific microscope modality. This requires robust algorithms for detection and tracking of image events and statistical methods for the integration of multidimensional image data in models of the underlying molecular process. Most recently the lab has coined the notion of “computational multiplexing” as an approach to integrate by statistical means image events observed sequentially in different imaging experiments to reconstruct the interdependence of a series of molecular activities that cannot be observed simultaneously [7]. This technology has opened the door to an image-based reconstruction of large and complex molecular pathways in living cells.

Until now our lab has been writing software with home-knitted interfaces to the file system to store and organise data. We have established common practices for image data management and data formats to ensure compatibility between our software packages. Most of our software can be downloaded via the lab website, an offering to the community that is used heavily.

Our interest in collaborating with the OMERO team is to integrate with the OMERO package some of the image analysis software that is generic and thus amenable to wide-spread use. The first immediate goal until April 2013 is to package a generic particle tracking software for diverse applications we have published, e.g. single molecule imaging [8], tracking of microtubule dynamics with +TIP markers [9], single cell tracking in populations [10], etc. These functionalities are currently distributed over different software packages, although they all use the same basic mathematical framework. The switching between these applications will be controlled by a wizard that guides the operator through application specific choices of motion models and parameters. The wizard will communicate with OME to load raw data and deposit results. It will also offer several viewers and trajectory post-processing toolkits.

Further information is available on the Danuser Lab website

Gaudenz Danuser is a Professor of Cell Biology at UT Southwestern. Before, he directed research laboratories at ETH Zurich and at The Scripps Research Institute in La Jolla. Trained as an engineer (geodetic and electrical engineering), he entered the field of cell biology as a postdoctoral fellow in the Program for Architectural Dynamics of Living Cells at the MBL in Woods Hole. Since then, he has focused his research on the interface between chemical and mechanical signalling and structural adaptation that dictates the regulation of cytoskeleton functions. His lab develops innovative quantitative imaging methods to experimentally probe these processes and uses mathematical modelling to integrate the data in mechanistic systems analyses. His teaching activities at HMS focus on computational cell biology, molecular biomechanics and measurement theory applied to cell biological analyses. Together with Khuloud Jaqaman, Steve Altschuler, and Lani Wu, he also initiated a 10-day course at the MBL in Woods Hole dedicated to training mathematicians and computer scientists in the specific aspects of computer vision applications to cell and developmental biology.