Systems Biology in Nephrology:  SysKid Researchers at the European Renal Congress Reveal a Picture of Complex and Dynamic

»Omics« can, for instance, help researchers analyse the genome or all the proteins contained in a cell. Together with clinical and epidemiological findings these data provide not only new insights into renal function but also pave the way for the development of new strategies to combat chronic kidney disease.

The flow of data from the laboratories of geneticists and molecular biologists has grown into a flood in recent years. The twenty-five groups of researchers from fifteen countries who have been working together for the past five months on a large integrated research project known by the acronym SysKid aim to use the instruments of systems biology to channel and link these data in the field of nephrology and thus allow them to be utilised for medical research.

Genomics

»So-called association studies have in recent years allowed numerous genes to be discovered that play in a role in the development of chronic kidney disease«, Professor Rainer Oberbauer from the Medical University Vienna explains. The impact of these genes varies, how-ever. They have a mutual effect on one another and are also influenced by external factors – in other words, they display the typical traits of a »multi-factor disease«. The processes that lead to chronic kidney disease are much more complex than is generally assumed. Not least for this reason the predictability of how kidney disease will progress and how it will respond to treatment is limited. »Our goal must therefore be to diagnose the processes that cause the disease in an individual patient so that we can target treatment more precisely”, Oberbauer says.

Transcriptomics

»Analysis of the genetic information transcribed in the genetic transmitter RNA clearly shows that thinking of disease in terms of single factors – one gene is responsible for each disease – makes no sense for the overwhelming majority of diseases«, says Prof. Dr. Gert Mayer from the Medical University Innsbruck. »What actually happens is that whole networks change«, the nephrologist continues. »We can assume that diseases are usually the result of an imbalance between ‘protective’ and ‘harmful’ networks«, Mayer continues, describing the new approach of researchers. Even chronic diseases should be seen as a kind of ‘balance’ between protection and damage, which should also be taken into account in treating them.

In order to test such hypotheses researchers need to order the huge amounts of data obtained from analyses of genes and proteins to find out which of them are significant. To do this requires not only complex methods from bioinformatics and systems biology. »Ultimately it will be necessary«, says Gert Mayer, »to test the findings provided by these new technologies in conventional systems«.

Proteomics

SysKid research teams have already done this in one field, as Professor Harald Mischak from the Biotech company mosaiques diagnostics in Hannover reports at the Munich congress. Together with scientists in Denmark and Australia, Mischak’s team analysed patterns of particular protein substances, so-called biomarkers, in urine samples from diabetes patients, which doctors had collected in long-term studies over many years and frozen for research purposes. The scientists were able to show that changes in protein patterns in urine allow kidney disease to be detected at a very early stage, long before conventional tests would provide any indication of the disease. »If the disease is treated in this early phase progress could be prevented or even aboided«, Mischak says.

Systems biology

»We are optimistic, that the ‘omics revolution’ will provide us with sets of data that will enable us to analyse even complex diseases«, says Dr. Bernd Mayer, managing partner of the R&D company emergentec biodevelopment GmbH, Vienna, whose team is coordinating SysKid. But Mayer is equally convinced that the researchers still have to do their homework if they are to use bioinformatics to optimise the management and integration of already existing and new data: »Method development therefore has an important role to play in SysKid«. Nevertheless, systems biology, which seeks to use new insights into networked and dynamic life processes to piece together a complex puzzle, is still in its infancy. »I am optimistic, however”, says Mayer, making a bold prediction, »that systems biology will have a major influence on clinical research in the future and that the manifold possibilities offered by bioinformatics for analysis and integration of data will have a big role to play in this«.

The keywords are »omics« and »systems biology« in nephrology
»Only once we begin thinking in terms of networks and see the cell, the organ and the organism as a dynamic system that tries to maintain a stable balance (and it has many ways of doing so) will we make the advancements necessary to develop diagnostic, preventive and therapeutic strategies to combat chronic kidney disease.«

Prof. Dr. Gert Mayer, Department of Internal Medicine IV, Nephrology and Hypertension, Medical University of Innsbruck, Austria

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