Building a picture of biological robustness Complex biological systems are subject to many perturbations, yet they show great robustness during development. Researchers in the RobustNet project are using C. elegans as a model system to investigate the underlying factors behind this robustness, and also model infections by emerging pathogens, as Dr Michalis Barkoulas explains A biological system is subject to many perturbations during development, including both environmental and genetic variations, yet such systems are able to cope with this variability and produce a consistent output. Based at Imperial College in London, Dr Michalis Barkoulas is the Principal Investigator of the RobustNet project, an EU-funded initiative investigating the underlying mechanisms behind biological robustness. “In particular we’re looking at developmental robustness – for example, thinking about how a fertilised egg is transformed into a multi-cellular individual. We take it for granted that this is going to work, but we shouldn’t lose sight of the fact that this is pretty remarkable, given all the perturbations that biological systems face,” he outlines.
C. elegans The C. elegans nematode is being used in the project as a model system in research. C. elegans is a eutelic organism, meaning that it produces a precise number of cells; complete lineage maps have been developed for all different cell types, STUDYING MECHANISMS OF DEVELOPMENTAL ROBUSTNESS AND NOVEL OOMOCYTE INFECTIONS IN C. ELEGANS Doctor Michalis Barkoulas Group Leader | Imperial College Department of Life Sciences SAF building, office 607 SW7 2AZ, London T: +44 (0)207 5945227 E: m.barkoulas@imperial.ac.uk W: https://www.imperial.ac.uk/ people/m.barkoulas : https://mobile.twitter.com/ barkoulab?lang=en Dr Michalis Barkoulas obtained his PhD on plant evolution and development from the University of Oxford. He started working on questions related to C. elegans developmental patterning as a postdoctoral researcher at the Ecole Normale Superieure in Paris. He is currently a Lecturer at Imperial College in London and his group investigates the robustness of various developmental systems and host-pathogen interactions.
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enabling researchers to trace the developmental history of any cell in the adult all the way back to the zygote. “Based on these reproducible developmental lineages, we can study the mechanisms that are actually behind this robustness,” says Dr Barkoulas. One major area of
prioritise them and how do we identify those that are likely to help us derive more general principles,” says Dr Barkoulas. The wider goal in this research is to investigate how genes stabilise developmental outcomes, in order to establish a framework for phenotypic buffering. This could lead to new insights into the underlying causes of disease, and how mutations cause specific conditions. “A lot of disease can be viewed in the context of the buffering of normal physiological states. For example, we study cell numbers, which is very relevant to cancer,” says Dr Barkoulas. “We hope that some of our findings, such as identifying points of fragility in C. elegans gene networks, will be relevant for other biological systems and disease in the long run. For example, cancer is notoriously robust against therapeutic treatments but it is still unclear how cancer cells gain this robustness.”
We hope that some of our findings, such as identifying points of fragility in C. elegans gene networks, will be relevant for other biological systems and disease in the long run interest in the project is the consistency of cell numbers in the population. “If you compare animals in controlled settings, they typically have the same number of cells,” continues Dr Barkoulas. C. elegans nematodes all have the same genetic composition. However, mutations can be induced where certain genes and pathways are perturbed, leading to animal-to-animal variation in the population. Dr Barkoulas and his colleagues are using genetics to discover the full spectrum of mutations that can give rise to variability in the model organism. “We are trying to find out what are the genes leading to developmental variability and how they work,” outlines Dr Barkoulas. These screening techniques are unbiased, so researchers hope to identify both pleiotropic factors, which are not specific to a particular developmental system, and more specific factors for the tissues investigated. “These screens provide a lot of data on new mutations; the question then is how do we
Oomycetes Researchers are also using C. elegans to model infections from a particular class of understudied organisms called oomycetes, the most famous of which is Phytopthora infestans, which causes potato blight. For the first time Dr Barkoulas and his colleagues have two oomycetes in culture infecting C. elegans; this opens up new areas of research. “We study questions related to innate immunity. How does C. elegans recognise the presence of these pathogens in the environment? What sorts of responses does it trigger as protection? And how do these pathogens manage to circumvent these responses to kill nematodes?” he says. This research holds wider importance in terms of understanding disease. “This is particularly important as some of these oomycetes also infect humans, especially in tropical regions, and these infections are currently incurable,” explains Dr Barkoulas.
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