Until very recently, the complexity of living systems was perceived primarily as an impediment to studying them. Accordingly, the standard approach of mainstream Molecular Biology was to reduce this complexity using isolated and purified components proteins, nucleic acids and metabolites. Such reductionist approaches are now being complemented by novel avenues for addressing the multitude of biological problems from the perspective of the whole system. For quite a while now, computational processing of heaps of biological sequence data has assisted virtually all scientists in formulating their experimental questions and interpreting their results. The big breakthrough of recent times has been the spread of high-throughput DNA sequencing technologies that have allowed the complete determination and archiving of the whole genetic complement of a number of individual species from bacteria to humans and through metagenomics even complete ecosystems. DNA sequencing efforts are still on the rise: while sequencing the first bacterial genomes required the effort of dozens of people working full time for many months, the same can now be achieved in a few hours. Massive DNA sequencing was in fact the turning point that opened the door to an era that now includes proteomics, metabolomics, interactomics and many other -omics. The possibility of amassing at once large amounts of data on every biological system is now taken for granted. As a consequence, we live in an age of information overload, with too many genes, too many reactions, too many sequences and too many numbers, which we individuals cannot keep up with. The challenge now, in the words of Sydney Brenner, is to translate data into knowledge and knowledge into understanding.
On top of all this, microbiology has to face the overwhelming diversity inherent to its field of action. While this diversity is fascinating and holds great promise for the applied use of many microorganisms, it also adds another level of complexity further preventing Microbiology from joining the selected club of the hard sciences. The results generated in one microbial system frequently lack universal value, thus limiting the worth of the resulting knowledge. Comparative genomics reveals that contrary to the celebrated Monod's remark on Escherichia coli and the elephant what is true for one E. coli strain may not even be true for the next E. coli strain. An additional downside of having too much diversity is the lack of suitable formats to compare and match results arising from different experimental systems. There is little consensus on the names of the genes, on the conditions of the experiments, on the definitions of key parameters, on the activities of the various enzymes, etc. It is in this context of information overload and lack of proper formatting that Systems Biology and its emphasis on numerical descriptions and standardization comes to the rescue.
Systems Biology is an umbrella concept that includes a range of efforts to take live organisms to a level of quantitative comprehension. The distinct angle of Systems Biology is not about managing many types of data, but about dealing with complexity as such, without breaking it down to smaller bits and pieces. This is a serious methodological [and epistemological] change, as Systems Biology leaves behind the reductionist approaches that have permeated much of modern Biology and attempts instead to see live organisms as a whole. Systems Biology can be seen both as a top-down core discipline that can be projected into a diversity of biological questions, as well as a bottom-up collection of approaches on various organisms in a quest for common rules and quantitative languages. Such a creative tension between top-down modelers and bottom-up experimentalists [which can be detected in every Systems Biology meeting] is one of the distinctive and energizing aspects of this now thriving field.
This special FEMS Microbiology Reviews issue on Microbial Systems Biology includes papers that tackle both methodological and fundamental aspects of how complex biological functions emerge from simpler components. In this respect, little by little, microorganisms are leaving behind their status as mere model systems or cell factories and are becoming a genuine source of pivotal biological questions that belong to the core of modern Biology. Note that the list of contributions in this issue is by no means limited to E. coli as a model organism, but includes a diversity of central systemic questions where the use of microorganisms for both modeling and experimentation sheds considerable light on the issues at stake. The selection of topics reflects mostly a bottom-up approach. We believe this will make the issue more palatable to the predominantly wet-lab readership of the journal. Several top-down approaches [mostly on metabolomics, fluxomics and interactomics] have been the subject of recent reviews and are generally well covered in the literature. Space limitations have also prevented us from including any discussion of the breathtaking progress on yeasts and fungi, systems that will surely deserve a dedicated issue in the future. The emerging field of viral and meta-viral Systems Biology, regrettably, had to be left out as well. Still, we are proud of the contents of this volume and hope that, despite all the limitations, these reviews will inspire readers to look for new ways to approach old problems, raise new questions and eventually understand [and even reprogram] the logic of their favorite microorganisms!
© 2008 Federation of European Microbiological Societies.