By Jim Beynon
Life is complex, probably the most complex subject for science to unravel. At the core of the system are the DNA molecules that encode the blueprints for life; in humans this contains the codes for 20,000 to 25,000 proteins. Some of these proteins interact to control the expression of the genes and only subsets of the genes are expressed in any one cell type. So to be a brain or kidney cell, different combinations of the blueprint need to be turned on or off. Interwoven with this process are more levels of control in that more than one regulatory protein can regulate expression of any gene and structural changes to the DNA itself; also a whole suite of small molecules similar to DNA exist that alter when and where any gene can be expressed. So controlling the expression of the blueprint is complex. However, in addition, proteins can interact with one another in a range of different ways depending on the environment in which the cell is existing and the consequence of many cellular processes produces or modifies chemicals (or metabolites), the profiles of which will be different in varying cell types. The key to understanding the complexity of living things is to understand the interactions between all these components that lead to a successful functioning cell. However, the challenge does not stop there but extends to the world that we see daily, and to understanding how species interact with one another to create life-sustaining communities. At each stage, it is interactions between many different components that result in a viable living organism or the community of species within which it will exist.
A major impact that the human species is having on the planet is causing global warming resulting in a changing environment. This will be a major challenge to crop scientists in the coming decades as it will place our food producing plants under a range of new stresses that will affect their productivity. These environmental changes will include higher temperatures, altered growing seasons and the arrival of new pests and disease. Plants’ responses to environmental changes such as drought, disease and pests are complex. The model plant, Arabidopsis, contains some 30,000 genes, more than humans but less than many crops. When exposed to environmental stress, several thousand of these change whether they are on or off compared to growing in benign conditions. Within this complex response some of the genes produce proteins that control the expression of others and, hence, are key players in the response. Identifying these key controlling genes in the face of all this complexity is a major challenge. This requires collaboration between biologists, statisticians, engineers and mathematicians to bring new analysis techniques to enable biology to begin to unravel this complexity. This in itself is a major challenge to the theoretical sciences as many techniques are not capable of dealing with so many variable components. However, using this interaction between scientists from different backgrounds, we have created models of gene networks with the key genes at the centre of spider web like predicted gene/protein interactions. We have now shown that preventing the function of many of these genes, predicted to play a significant role in stress responses, results in a change in the way the plants respond to environmental stress. This suggests that bringing diverse approaches to building models to understand the complexity of these responses has successfully de-convoluted some of the complexity in the system.
Yet this is only the beginning, as we are only looking at one stress, but in the crop field the situation is much more complex as plants are exposed to many stresses at once. Therefore, we are extending these studies to understand how these gene networks respond to multiple stresses. However, changes in levels of gene expression is only one component of the complexity. Another key network involved in plant environmental responses is the interaction between the proteins encoded by the genes. When pathogens (disease-causing bacteria or fungi) attack plants, many introduce proteins into plant cells to disrupt the protein networks of the host. We are working with leading groups in the USA to reveal the complexity of the protein interactions between the 25,000 plus proteins in the model plant and how the pathogen proteins disrupt this complex network. Identifying the targets of the pathogen proteins will lead to new ways of protecting plants from disease.
The complexity of living systems may seem contradictory to having a reliable and easily maintainable method to maintain life. Nevertheless, it is this complexity that gives living systems robustness. It prevents the failure of one component disrupting the functioning of the system as a whole. Modulating the response to a particular stress prevents overreaction, acting as a buffer to stop catastrophic outcomes unless that stress becomes overwhelming. Having many forms of particular proteins or altering their relative expression levels enables members of a species to be diverse, so maintaining the ability to survive even when the environment is changing. So complexity of interactions is fundamental to the successful evolution of life and it remains one of the greatest challenges for mankind to understand.
‘The key to understanding the complexity of living things is to understand the interactions between all the components that lead to a successful functioning cell.’
Jim Beynon is Chair of Plant Systems Biology at Warwick HRI. He works on host-pathogen interactions in the field of plant science research, and has been building key genomic resources to exploit the new systems biology approach to science, involving extensive collaboration with consortia in Belgium and France.
Professor Jim Beynon