Over the past decade our understanding of biology has benefitted considerably from the now mature fields of genomics and proteomics. Both these fields provided biologists with a wealth of information by cataloguing all genes present in many organisms as well as the proteins produced from these genes. With this information, biologists were able to form new and complex hypothesis of how biological systems function. Not only did basic science profit from these developments, but the general quality of life has also been impacted through the development of novel diagnostics and drugs. Such novel approaches to predictive and preventive medicine arose in part from a new understanding of the genes and proteins involved in disease, but also because our basic understanding of biology improved tremendously.
Systems Biology arose as a logical consequence of the information gained from genomics and proteomics. With a fairly comprehensive catalogue of the building blocks of life in hand, the next pertinent question that arose was how these building blocks interact on a global scale. Even though Systems Biology may not as of yet have a universally agreed upon definition (as can be seen by the heterogeneity of SystemsX.ch RTD projects) the goal of Systems Biology is clear, albeit incredibly ambitious: Systems Biology aims to make life predictive. In other words, we are working on being able to simulate life in silico, from a minimal set of information such as the genome sequence of an organism. Such simulations would have to be capable of predicting genes and their translated products or proteins, how these proteins fold into functional molecules and how this plethora of proteins interact in a cell, in turn giving rise to complex functional networks and structures. At this stage formation of tissues, organs and entire organisms could in principle also be predicted, including the interactions amongst organisms in whole ecosystems. The current state of the field is obviously far from this goal, but the consequences of achieving this “digital biology” will be tremendous even if only small portions of the above dream come within reach in the next decade. But in order to make progress towards “digital biology”, biologists must understand how biological systems function in the first place.

In DynamiX we are aiming to understand how proteins interact amongst themselves and with DNA by studying the model organism S. cerevisiae (bakers yeast). The reason for choosing yeast as our model system is multifold. Firstly, it is a relatively simple eukaryotic organism containing a modest number of DNA bases, genes and proteins (13,000,000 DNA bases, ~6,275 genes, and ~5,800 proteins). Furthermore, a vast knowledge base is available, as yeast has served as a model organism for over 30 years. But despite its “simplicity”, many functional mechanisms such as cell division, recombination, replication, metabolism, and epigenetics are conserved between yeast and higher organisms. Despite the long history of yeast as a model organism, the above-mentioned mechanisms have almost exclusively been measured in isolation and rarely quantitatively. One goal of DynamiX is to measure the entire protein repertoire and its dynamics in vivo to understand what the important parameters are that allow such complex networks to function so robustly. Additionally we are interested in developing models, which will allow us to predict when and to what level any given protein is being expressed in yeast, bringing us one step closer to predictive in silico biology. Obviously these tasks are quite complex and can only be achieved through the development of new technologies.

Biology in general has always been, and will likely remain, a technologically limited field. New and drastic discoveries in biology are almost always preceded by the development of new technologies. Take for instance the development of the microscope, which sparked the field of Biology, and the more recent development of high-throughput sequencing, which impact is already being felt strongly across almost every biological field. In DynamiX we are actively developing and applying state-of-the-art microfluidic technology, which allows biologists to perform experiments with unprecedented scale and accuracy. One such platform we are currently developing will allow us to image the dynamics of all proteins present in yeast on the single-cell level, by obtaining more than 430’000 high-magnification images (or 1.4TB of data) per day. The technology development, the basic biology, and the vastness of the data pipeline require that a diverse team of researchers tackle such a project. In DynamiX we bring together biologists, computational biologists, bioinformaticians, physicists and bioengineers to provide the necessary breadth of knowledge. Furthermore, because of the integrated nature of the research conducted, our graduate students and Post-Docs involved in the DynamiX project will be exposed to a wide variety of fields allowing them to gather quantitative as well as experimental expertise across several disciplines.

Overall we are convinced that a systems approach to biology is absolutely necessary in order to make headway in our basic understanding of how biological systems function. This knowledge will naturally diffuse and translate into benefits to the general public, through developments in predictive and preventive medicine. These advancements will be primarily due to our increased understanding of how biological systems behave and through the development of novel and advanced technologies.

• Publications by SystemsX.ch (overview)
  

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