Systems Biology and Synthetic Biology: Understanding Biological Complexity on the Critical Path to Personalized Medicine

Abstract

It has been suggested that personalized medicine era is fast approaching based on recent applied genomics and life sciences findings. But are the tools to enable personalized therapeutics and multiplexed diagnostics at hand? Nearly a decade after the first full publication of the human genome sequence and the media hype around numerous related medical promises, biologists are still facing crucial questions about biological complexity and its reverse engineering. A biological system is considered more complex not on the basis of the number of its components but rather on the number and strength of interactions between the components. The challenge is to obtain a comprehensive picture of cell functioning. The general mechanisms regarding the cellular information have been now uncovered. The past decade has seen small RNAs on the news, their cellular importance being directly related to an early phase of life evolution. Besides the discoveries of siRNAs and riboswitch RNAs, biologists have appreciated the importance of taking biological noise into account. Systems biology approaches are aimed at understanding the emergent collective properties of the biological constituents of the cell or the whole organism. Synthetic biology is aimed at engineering living systems to create living micromanufactures and bio-derived nanomachines. The recent report in May 2010 of the creation of new Mycoplasma mycoides cells with a synthetic digitized chromosome by Gibson and co-workers is the first major milestone in this new biotechnology era. Current conceptual changes in systems and synthetic biology are illustrated in this paper with several examples related to personalized medicine: from diagnostics to individualized drug therapies. Keywords: Biological complexity, biological noise, multi-omics, personalized medicine, proteogenomics, synthetic biology, systems biology, phenomics, Mycoplasma mycoides, chromosome, omics, Haemophilus influenzae, metagenomic projects, microbiome, single-nucleotide polymorphisms (SNPs), pyrimidine biosynthesis, Cystic fibrosis, Transcriptomics, oligonucleotidic probes, micro-arrays, protein-protein interactions, mass spectrometry, polypeptide chain, proteolytic cleavage, Geobacter sulfurreducens, babelomics, Saccharomyces cerevisiae, Sorghum bicolor, non-protein coding RNAs (ncRNAs), pseudouridine synthases, Read Only Memory (ROM), RNA polymerases, spliceosomes, microelectronics, endonucleolytic enzymes, hyperthermophilic polymerases, enterobacterium, pseudotaxis, artemisinic acid, inhomogeneous mixture, serine, threonine, tyrosine residues, phosphatases, cerebrospinal fluids, tumor biopsies, chemogenomics, toxicological, Single-nucleotide polymorphism