Section: Overall Objectives

Overall Objectives

Cells are seen as the basic structural, functional and biological units of all living systems. They represent the smallest units of life that can replicate independently, and are often referred to as the building blocks of life. Living organisms are then classified into unicellular ones – this is the case of most bacteria and archea – or multicellular – this is the case of animals and plants. Actually, multicellular organisms, such as for instance human, may be seen as composed of native (human) cells, but also of extraneous cells represented by the diverse bacteria living inside the organism. The proportion in the number of the latter in relation to the number of native cells is believed to be high: this is for example of 90% in humans. Multicellular organisms have thus been described also as “superorganisms with an internal ecosystem of diverse symbiotic microbiota and parasites” (Nicholson et al., Nat Biotechnol, 22(10):1268-1274, 2004)) where symbiotic means that the extraneous unicellular organisms (cells) live a close, and in this case, long-term relation both with the multicellular organisms they inhabit and among themselves. On the other hand, bacteria sometimes group into colonies of genetically identical individuals which may acquire both the ability to adhere together and to become specialised for different tasks. An example of this is the cyanobacterium Anabaena sphaerica who may group to form filaments of differentiated cells, some – the heterocysts –specialised for nitrogen fixation while the others are capable of photosynthesis. Such filaments have been seen as first examples of multicellular patterning.

At its extreme, one could then see life as one collection, or a collection of collections of genetically identical or distinct self-replicating cells who interact, sometimes closely and for long periods of evolutionary time, with same or distinct functional objectives. The interaction may be at equilibrium, meaning that it is beneficial or neutral to all, or it may be unstable meaning that the interaction may be or become at some time beneficial only to some and detrimental to other cells or collections of cells. The interaction may involve other living systems, or systems that have been described as being at the edge of life such as viruses, or else genetic or inorganic material such as, respectively, transposable elements and chemical compounds.

The application goal of ERABLE is, through the use of mathematical models and algorithms, to better understand such close and often persistent interactions, with a longer term objective of becoming able in some cases to suggest the means of controlling for or of re-establishing equilibrium in an interacting community by acting on its environment or on its players, how they play and who plays. This goal requires to identify who are the partners in a closely interacting community, who is interacting with whom, how and by which means. Any model is a simplification of reality, but once selected, the algorithms to explore such model should address questions that are precisely defined and, whenever possible, be exact in the answer as well as exhaustive when more than one exists in order to guarantee an accurate interpretation of the results within the given model. This fits well the mathematical and computational expertise of the team, and drives the methodological goal of ERABLE which is to substantially and systematically contribute to the field of exact enumeration algorithms for problems that most often will be hard in terms of their complexity, and as such to also contribute to the field of combinatorics in as much as this may help in enlarging the scope of application of exact methods.

The key objective is, by constantly crossing ideas from different models and types of approaches, to look for and to infer “patterns”, as simple and general as possible, either at the level of the biological application or in terms of methodology. This objective drives which biological systems are considered, and also which models and in which order, going from simple discrete ones first on to more complex continuous models later if necessary and possible.