The discovery of the DNA was certainly one of the biggest breakthroughs in science history. But in my humble opinion, the paradigm shift in research methodology was caused by molecular biology techniques. With the use of such techniques, perfected and advanced over time, the field has produced major discoveries regarding regulation of our activities. During this period of biological research, there was a rush to discover the genetic cause of any anomaly observed biologically, or even sometimes, stretched to more abstract concepts of personality, even probing political ideology (ref). But this change in the course of research also resulted in accumulation tons of data, a lot of the times overlapping. Every single bio-molecule was being carefully studied, and as naturally happens, scientists got too lost in the molecules they were studying. Similarly, the sequencing and bioinformatics field has suffered the same problem – there were just tons of genomic data that needed to be documented (ref). The solution seems to lie in the field of systems biology, since it became “a movement of its own” since 2000 (ref).

 

A perfect example of the use of this concept is reflected in the works of Dr. Salil Lachke (Univ. of Delaware). Dr. Lachke studies the genetic and molecular cause of cataract formation using bioinformatics and animal models. How does he bridge the gap between these seemingly far-away fields? His lab has developed a systems biology tool called iSyTE (integrated Systems Tool for Eye gene discovery) to identify candidate genes based on patient-derived data on cataract formation and to elucidate regulatory gene networks (RGNs) behind eye development. Because his work is extensive (Pubmed), it will not be possible for me to describe all of it. So I would like to talk about two key projects that he did, which in my humble opinion, speak out for the significance of his work. In regards to eye development, he has used iSyTE to build an information network known as the “Developmental Oculome“. Based on the published literature on dynamic RGNs and protein networks interacting during eye development, this project aims to accumulate all the relevant information on molecular interplay and create the big picture. Similarly, his work in cataract formation has resulted in the identification of the Tdrd7 gene, a mutation in which results in glaucoma and cataracts (ref). TDRD7 is a RNA binding protein that are critical for the cytoplasmic RNA granules to properly regulate mRNAs post-transciptionally for organogenesis. He showed that null mutations in this gene results in glaucoma and cataract formation in mice models and even causes arrest of spermatogenesis (ref). He has also shown that targeted RNA sequences can be used to reverse this mutation and restore eyesight lost due to cataract formation (unpublished*).  In the course of this research, he has also identified other genes that have been seen to cause congenital cataract formation (ref, unpublished*). Interestingly enough, he has also identified the skin to be facilitating the mating of Candida albicans,   a causal agent of oral and genital infection in humans (ref). It is rather amazing to observe how he brought together fibroblasts present in the skin, and the opaqueness of C. albicans cells to shed light on the opacification of the lens, due to genetic mutations in lens fiber formation. He literally “cleared up the big picture” on eye disease and development.

 

Just as Dr. Lachke is trying to provide a more dynamic landscape of the numerous molecular interactions behind development, a recent study has provided the background for studying such interactions in multiple conditions, rather than a single condition used so far. Large-scale changes in gene-gene, gene-protein and protein-protein interactions can be studied, in the future, using this approach. As stated in the paper, the researchers’ approach was to investigate the parts of the system to be most affected due to a disturbance. This study essentially bridges the nature vs. nurture duality by pointing out differences within protein-protein and protein-gene interactions, resulting from an environmental stimulus, and also the differences in the gene-gene interactions resulting from a mutation in the same context. With increasing developments in both high-throughput data production, the field of differential network biology is a rapidly expanding tool aiding in studying DNA damage response, different disease states, and even on a macro scale, relationships between organisms based on genetic data.

 

Thus it is of no surprise that systems biology is a vital driving force in the paradigm shift observed in current biological research, just as molecular biology had done in the previous century. It will be through systems biology that we understand ourselves and our surroundings in a bigger picture, for as Linas Pauling said “Life is a relationship among molecules and not a property of any molecule”.

 

*The unpublished data was taken from a lecture by Dr. Lachke at Thomas Jefferson University on Feb 8, 2012 that I attended in person. 

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