21 May 2008

Workshop on Computational Morphodynamics

Meeting Goals

The goals of the workshop were to:

To provide a forum for cross-fertilization of ideas across campus, i.e., a chance for members of different groups working on different problems related to morphodynamics to meet with one another and discuss common problems, directions, and goals;

Assess the current state of the art of computational modeling of morphodynamic problems in biology;

Assess the needs of the Caltech community to further the study of morphodynamics;

To determine what kinds of computational tools and/or techniques are available or might be needed to help biologists further understand morphodynamics;

To identify the types of problems that are currently being studied on campus;

To identify what kinds of problems might be helped by additional modeling;

To assess the modeling needs of the community in regards to the relationship between morphology, geometry, physics, and regulatory networks;

To assess the need for further inter-group and inter-disciplinary research collaborations, grant-applications, group meetings, journal clubs, tutorials, training, courses, etc.

The term “Caltech Community” refers to researchers working on campus and their close collaborators working at other institutions.

Summary of Workshop Presentations and Discussions

Note: Because much of the work discussed centered on current research and unpublished results only very brief summaries of the material are presented. In some case references to or results taken from published results are given, but otherwise no original research actually presented at the meeting is shown here. It is to be emphasized that this was a workshop and not a research symposium.

Elliot Meyerowitz provided some introductory comments and gave a brief definition of computational morphodynamics, and mentioned some of the groups doing research in this are such as the computable plant project.

Marcus Heisler (Meyerowitz Lab) talked about linking biochemical signalling with mechanical models to develop a more comprehensive description of growth patterning in the shoot apical meristem. He obtains dynamic images of cell division and movement via a laser scanning “confocal microscope”: and utilizing various Green Fluorescent Proteins. Of particular interest is the development of microtubules that form the cytoskeleton, such as those described by the Shaw Lab at Indiana ; the importance of Auxin for cell signalling as described by Reinhardt’s Group in Switzerland; and studies of meristem architecture being performed by Jan Traas' group in Lyon.

David Sprinzak (Michael Elowitz lab) discussed the development of fine grained differentiation patterns during development in terms of a framework in which networks are reconstructed in mammalian cells [ Sprinzak & Elowitz, Nature 438:443-8 ]. Synthetic circuits can be used as simple in vivo models to explore the relation between the structure and function of a genetic circuit. An example of notch-delta signalling was given, similar to the model of [ Collier et al. JTB 183:429-46 ] which reconstructs various checkerboard-like patterns.

Melissa Pope, Ehsan Jabbarzadeh, and Keiichiro Kushiro (Anand Asthagiri group) described how various aspects of cell adhesion affect epithelial patterning during development. The physical interactions of a cell with its environment includes both cell-cell interactions and interactions with an an extracellular solid-state matrix of proteins. In addition to providing a physical platform, cell-matrix adhesion also stimulates various biochemical signals and networks. Their lab is engineering physical platforms that elicit similar control over cell behavior and using them to study mammalian cell behaviors and pattern development.

Eric Mjolsness discussed the need for morphodynamic mathematical frameworks. A large number of frameworks have been proposed and successfully used to described various aspects of morphodynamics, including: generalized reaction networks; fixed cells; Turing models; PDE’s that describe cell growth and polarity; cellular compartmental models including weak spring systems, finite element descriptions, and lively cell complexes; spatially stochastic approaches; and unified approaches such as variable structure grammars. [for a review see Mjolsness, J Plant Growth Regulation 25:270-277]. He also proposed a definition of computational morphology: the attempt to answer the question, “How do biochemical and informational processes determine major changes in the morphology of living organisms?“

Alex Cunha of the Caltech Center for Advanced Computing Research summarized many of the image processing techniques that are being used on campus to do image analysis; filtering; segmentation; and de-noising. He referred to the paper by [Buades, Coll, & Morel, Multiscale Modeling and Simulation, 4:490-530] as providing some standard algorithms.

Boris Shraiman (UCSB/KITP) discussed the relationships between mechanics, growth, size and pattern control. He talked about how morphogen gradients affect the development of the fly wing [ PNAS 104:3835-3840 ] and the importance of mechanical feedback as a growth regulator [ PNAS 102:3318-3323 ]. During the discussion he also posed a question for us in our research: are we looking for universality or computational efficiency (in our software/analysis/models)?

Greg Reeves (laboratory of Angela Stathopoulos discussed projects in which he is studing the spatial gradients of the dorsal protein in drosophila. The development of the dorsal/ventral protein in drosophila occurs as a result of a gradient that develops in the nuclear transcription factor called Dorsal. Dorsal is a maternally deposited rel-containing transcription factor that is present in a nuclear gradient within the early Drosophila embryo.

Ingmar Riedel-Kruse discussed his studies of synchrony dynamics of the segmentation clock in drosophila and how it affects patterning in the embryo. [ ref: Science 317:1911-1915 ].

The following gives a summary of points that were brought up during the final discussion.

To understand shape formation one needs to understand (among other things): (1) cell/cell interactions and (2) cell/substrate interactions.

This is a diverse and widely multidisciplinary field. Is there a way to turn some of this information into some sort of course. We need focused short courses that will help people understand enough of the analytic/computational techniques to be able to work with a modeler – much less be able to do our own modeling.

We need to have more interactions like this and sharing of information. It would be useful to have: journal clubs; multi-lab group meetings focuses on morphodynamics; tutorials on image analysis. It was decided that we would start having monthly super-group meetings with this aim.

Exchange of knowledge is essential. We need to know where to get information: even simple web pages with lists of course, books, articles, software, etc, that tell us where to go to find things out will help a lot. The BNMC offered to post the information that people suggest.

Is common tool development possible? There is not a single common tool being applied by all of these different projects, do we need one? If so what should it do and how?

There was a discussion of the question of how can modeling help us do better biology. A number of questions were raised: when do you have enough information to begin modeling; when is it OK to model; modeling can be expensive (because of the time required) and it might be cheaper to just do all the experiments; it takes a long time to get confirmation of a model. It was emphasized, however, that modeling is there only way one can get explicit about (even a simple) biological hypothesis.

Can we come up with a better name for this field than Computational Morphodynamics?