Modelling in four dimensions
By: Nuala Moran /
Tag: Modelling
From conception to birth, death and beyond, the human body is all about change. Thus, a key issue in modelling any aspect of the body is to move beyond static images of what any element looks like at any particular point, and factor in the fourth dimension of time.
Yaki Setty of the Computational Biology Group at Microsoft Research Cambridge has been working with academics in Israel to create a four-dimensional computer model that recreates the origin and formation of the pancreas in a mouse embryo.
“Our overall aim is to devise a generic platform for modelling any organ. Eventually, it should be possible to create such models in a week, or an hour,” said Setty. “The key is to determine what is the right level of abstraction.”
Organogenesis – the process by which organs develop – involves precursor stem cells proliferating, differentiating and organising themselves to form a functioning structure. But until now, understanding of the development of the pancreas, or any other organ, was based mainly on two-dimensional, static images captured in a time sequence. This reveals nothing about the emergence of the 3-D shape, nor of the dynamics that drive the process.
“The program gives a virtual real-time view of the growth of the pancreas from a few isolated stem cells to an integrated structure.”
Working from known mechanisms and processes, Setty and his colleagues have developed a 4-D simulation of pancreas development. When the program is run it gives a virtual real-time view of the growth of the pancreas from a few isolated stem cells to an integrated structure.
The model is interactive. This means that the signal pathways that are activated in the model can be altered, resulting in altered patterning as the pancreas develops. In other words, the model can be used to test hypotheses about the specific factors that drive organogenesis.
While such experiments carried out by computer programs cannot yet replace live experiments, they can inform them, saving time and resources. “Initial applications would be for ‘in silico' [computer] simulations in research and drug development, using these models to reduce the use of animals,” said Setty.
“The program gives a virtual real-time view of the growth of the pancreas from a few isolated stem cells to an integrated structure.”
In the longer term, the researchers believe such in silico experimentation may lead to better understanding of the pancreas, and of diseases such as diabetes. It can also provide a starting point for computer models of the formation of other organs.
Since creating the initial model, Setty and colleagues have extended it further along the development pathway of the pancreas, to show the formation of islets cells, the bodies that are responsible for secreting the hormone insulin.
In addition, the robustness of the model has been tested by applying it to the development of another organ, in this case the gonad of the worm Caenorhabditis elegans. “This fits well into the system, which is especially interesting, given the two models representing two distinct organs from two evolutionarily diverged organisms,” Setty noted.
He added, “It shows there are common, underlying principles and that you can extend the approach and concepts in the mouse pancreas model to other species and other organs.”
The next stage might be to model the function of organs, but Setty said it is not certain that the approach used to model proliferation and structure is appropriate for function. “A better approach may be two separate models that intersect with each other.”
Reference: Four-dimensional realistic
modeling of pancreatic organogenesis,
by Yaki Setty, Irun R. Cohen,
Yuval Dor, David Harel, Proceedings
of the National Academy of Sciences,
Volume 105, Number 51, pages
20374–9, 23 December 2008