The swallowing organ of a transparent worm reveals the potential inherent in mathematical tools for the study of biological systems
The throat of a capillary worm may seem like a rather strange starting point for studying the complexity of life's processes, but there are good reasons to start there. A collection of unique features have transformed the worm in recent decades C. elegans A model animal is particularly popular, and in fact one of the most studied creatures in the animal kingdom. This impressive body of knowledge is the main reason that led two scientists from the Weizmann Institute of Science straight into the mouth of the worm, in their attempt to demonstrate the great potential of mathematical and algorithmic models in understanding the details of biological systems.
As part of their research, Dr. Dana Sherman and Prof. David Harel From the Department of Computer Science and Applied Mathematics A mathematical model of the behavior of the feeding organ of the worm, in a way that makes it possible to accurately analyze the act of swallowing on its many aspects. Beyond understanding the complex dynamics of ingestion, the scientists demonstrated in the study how computer simulations can simulate, within minutes, biological experiments that would have lasted for years in the laboratory, if they were possible at all.
The glory of the worm
C. elegans She became a sought-after talent in the research community due to her transparent body, her minimalist and elegant structure - only about 1,000 cells - and the great similarity between the biological pathways in her body and those in our body. All these made it an ideal research object for understanding biological processes - from cell differentiation to the study of the nervous system and aging processes. This is how the worm found itself at the center of many studies, which led to groundbreaking discoveries and even the awarding of several Nobel prizes. Among other things, she was the first of the multicellular creatures whose genome was completely cracked. In addition, its complete neural network was also mapped as well as the lineages of each of its cells.
Despite the in-depth knowledge of the biology of the worm, when Dr. Sherman and Prof. Harel approached the work, there was no satisfactory explanation for the action of its mouth - an organ composed of several dozen cells, which performs suction movements that allow the worm to feed itself. At the end of six years of research, the scientists succeeded To develop a model that comprehensively describes all the mechanisms that produce movement in the different pharyngeal areas of the worm, and is able to perform analyzes Computational both of the pharynx as a whole, and of the various parts that make it up.
between biology and mathematics
To build a model of a living organ, Dr. Sherman and Prof. Harel turned to classical mathematics, starting with a description of the most basic components of the pharynx and gradually building from them, layer by layer, the complete system. The various components and variables introduced into the model included, among other things, data on the different types of the pharyngeal muscle cells, the nerve cells that transmit signals to these muscles, the way the signals pass and the concentration of various ions in the muscle cells. In addition, the model also Description of the flow of liquids and food particles in the throat of the worm.
But why build a model of something that has already been built, and successfully, by nature?
"Computer scientists are used to building models in preparation for building the thing itself - from airplanes to pacemakers," says Prof. Harel. "Our model, on the other hand, is designed to explain the behavior of an existing complex biological system. If we manage to build a model whose behavior completely matches everything we know about the system on which it is based - the model can be run under different conditions, and thus, potentially, to witness the phenomena unknown. These findings pave the way for experiments in the laboratory, which can confirm or deny the predictions made by the model."
Between contraction and relaxation
After its assembly was completed, the scientists took the model for a test drive in order to check its accuracy, and what insights could emerge from it. This is how the scientists were able to explain, among other things, the regulating mechanism between the contraction of the pharynx and its relaxation. On the one hand, the contraction action occurs at different times in different areas of the pharynx and propagates at different speeds. On the other hand, the nerve signals that keep this action going spread very quickly, almost simultaneously, all over the pharynx. If muscle cell contractions closely followed the nerve signals that activate them, they should occur in an almost coordinated manner. With the help of the model, the researchers proposed a mechanism that explains this seemingly contradictory dynamic and offer a possible solution to the puzzle.
It also emerged from the model that cells stretching along the pharynx play a role in the action of swallowing, and not just a structural role as had been assumed until now. In addition, the model predicted that in tiny fortifications such as the capillary worm, the production of long-term electrical signals - such as those produced in its pharyngeal muscles - requires the involvement of additional ions besides calcium and potassium ions. Finally, the scientists used the model to conduct computer simulations simulating various hypothetical experiments. For example, they tested how changes in the size or geometric shape of the throat would affect the passage of food. The results of the "experiment" were received almost immediately, and demonstrated another advantage of mathematical models: they make it possible to carry out arbitrary manipulations on the object being studied, even those that are not possible in the laboratory.
The model's predictions may point to promising research directions - far beyond capillary worms - in a way that will make it possible to improve the understanding of the complexity of life mechanisms and the ways of functioning of whole organs. Dr. Sherman and Prof. Harel hope that the model they developed will also allow people from other fields to use mathematical models to study the functioning of biological systems and reveal the secrets of life in another way.
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