Summary

Biological systems are extremely complex. They are characterized by a massive interplay between large amounts of compo­nents over wide range of length scales of nanometers to kilometers and time scales of picoseconds to years.
Un­til recently a sys­tems biology approach was almost impossi­ble because of this complex­ity. However, re­cent technological develop­ments allow a para­digm shift from a reduc­tionist approach focused on simplification towards an ap­proach that allows us to investigate and ultimately understand the system as a whole.

The key question in systems biology is how cells and organisms operate upon interaction with  their external environment.

Answering this question will generate generic knowledge about the dy­namics of complex systems and quantitative and explanatory computer models based on ex­perimental data that help to answer important issues such as:

• how and to what extent are biological systems steered by external and to what extent by internal, structural processes; 
• how sensitive are biological systems for a perturbation of the  exter­nal environment; 
• how much redundancy  is present within biological systems to secure their stabil­ity; 
• how can biological systems be modified in a directed and predict­able fashion.

The unraveling of the dynamics of complex biological systems is feasi­ble with the help of new technological possibilities such as high throughput DNA sequencing, measurement of the activity of all genes of an organism (transcriptomics), analy­sis of proteins (proteomics) and analysis of all metabolites produced (metabolomics).

This data generation is then cou­pled to extensive data integration (bioinformatics), combined with cell biological methods such as advanced light micros­copy and supported by an enormous increase in computer power.

These technological developments have created an explo­sion of information about  living systems, ranging form cells to ecosystems, and give us close-to complete lists of all compo­nents and processes in organisms, including man.
Never before in history was it possi­ble to study the overwhelming complexity of life in such detail. This will have a large influ­ence on many fields within the life sciences: health of hu­mans, animals and plants, food produc­tion, safety and security, bio-energy and biodiversity.

The Faculty of Science of the University of Amsterdam (UvA) has the ambition to play an impor­tant role in Systems Biology at the European as well as the global level.
Therefore scien­tists of SILS and IBED, two research institutes of the Faculty, have joined forces in this field which is being supported financially by the Faculty of Science and the Ex­ecutive Commit­tee of the UvA since 2010.

Scientific case

Systems biology requires tight cooperation be­tween biologists, biomedi­cal researchers, mathe­mati­cians, physicists, chemists and (bio)informaticians. Their input is essential to integrate the available data and translate it to biological knowledge. 

To bring together this ex­pertise the Netherlands Institute of Systems Biology (NISB) was founded in 2007. In NISB SILS and IBED have bundled their forces with those of the Faculties of Earth & Life Sciences and of Sciences of VU University Amsterdam (VUA) and the Centre for Mathematics and Informat­ics (CWI).

Strategically NISB has had a great im­pact: 

• it obtained a start-up grant from NWO;
• it is the initiator of the Netherlands Consor­tium for Systems Biology (NCSB; www.ncsb.nl) that funds within NISB a  core modeling group;
• it is one of the initiators of the European Strategy Forum on Research Infrastructures (ESFRI) proposal that focuses on large investments in systems biology infrastructure;
• it is participating in two large sys­tems biololgy projects in the framework of ‘Biosolar Cells’ (www.biosolar.cells), and;
• NISB is an important participant in three European research projects on systwems biology: SysMO (www.sysmo.net), EraSysBio-Plus (www.erasysbio.net) and  FINSysB (http://www.finsysb.eu/).

Examples of SILS and IBED research projects that are expected to result in important break­throughs are: 

• analysis of gene expression, epi­genetic regulation of gene expression and folding of chromatin in relation to the function­ing of the genome. This project is aimed at targeted modifica­tion of eukaryotic cells, tissues and organs; 
• insight in mechanisms that counter­act disorders related to aging resulting in healthy aging; 
• sustainable production of biofu­els by cyanobacteria through a process that is economi­cally viable compared to fossil fuels; 
• adaptation of plants to cope with (a)biotic stress for sustainable food production; 
• gain­ing insight in the symbioses between the microbial gut flora and the human metabolism related to healthy food; 
• understanding of the anticipa­tion of complex ecosystems to tempera­ture and CO2 changes related to the conservation of biodiversity, and;
• the develop­ment of vaccines against life threatening fungal infection by Can­dida.

The Academic Medical Centre of the University of Amsterdam has decided to join this initia­tive through its research that focuses on a systems biology approach of the Meta­bolic Syn­drome, a combination of disorders that are related to obesity and the linked resis­tance to insulin. 

Key publications

1. Beninca E, J Huisman, R Heerkloss, KD Johnk, P Branco, EH van Nes, M Scheffer & SP Ellner (2008) Chaos in a long-term experiment with a plankton community. Nature 451: 822-825.
2. De Roos AM, T Schellekens, T van Kooten & L Persson (2008) Stage-specific predator species help each other to persist while competing for a single prey. Proc Natl Acad Sci USA 105: 13930-13935.
3. Mateos-Langerak J, M Bohn, W de Leeuw, O Giromus, EM Manders, PJ Verschure, MH Indemans, HJ Gierman, DW Heermann, R van Driel & S Goetze (2009) Spatially confined folding of chromatin in the interphase nucleus. Proc Natl Acad Sci USA 106: 3812-3817.
4. Vermeer JEM, JM Thole, J Goedhart, E Nielsen, T Munnik &TWJ Gadella (2009) Visualisation of PtdIns4P dynamics in living plant cells. Plant J. 57: 356-372.
5. Takken FLW & WIL Tameling (2009) To nibble at plant resistance proteins. Science 324: 744-746.
6. Young, BP, Shin, JJH, Orij, R, Chao, JT, Li, SC,  Guan XL, Khong, A,  Jan, E, Wenk, MR, Prinz, WA, Smits, GJ & CJR Loewen (2010) Phosphatidic acid is a pH biosensor that links membrane biogene­sis to metabolism. Science 329: 1085-1088.
7. TerBeek, A. and Brul, S (2010) To kill or not to kill Bacilli; opportunities for food biotechnology. Curr Opin Biotechnol. 21: 168-174.
8. Kolodkin A.N., Bruggeman FJ., Plant N, Moné MJ, Bakker BM, Campbell MJ, Van Leeuwen JPTM, Carlberg C, Snoep JL and Westerhoff HV (2010) Design principles of nuclear receptor signaling: how complex networking improves signal transduction. Mol. Systems Biology 6; doi 0.1038/msb.2010.102
9. Kramer G., Sprenger R.S., Nessen M.A., Roseboom W., Speijer D., de Jong L., Teixeira de Mattos M.J., Back J.W., de Koster C.G. (2010) Proteome-wide alterations in Escherichia coli translation rates upon anaerobiosis Molecular & Cellular Proteomics 9:2508–2516, 2010.
10. Duynhoven J. van, Vaughan E.E., Jacobs D., Kemperman R., Velzen E.J.J. van, Gross G., Roger L., Possemiers S., Smilde A.K., Dore J., Westerhuis J.A. and Wiele T. van der (2011) The metabolic fate of polyphenols in the human superorganism. Proc Natl Acad Sci USA 108: 4531-4538.