As the human genome project’s influence grows, one of the concepts that has emerged is complexity. Scientists including biologists have appreciated for some time that genetic networks drive development and biological responses. The cell’s responses to stimuli require and ever changing cast of proteins. The instructions for the protein sequences are encoded within the genome. If we could understand how this large cast of proteins is assembled into smaller pathways and responses we would be considerably further along. The parts list is long and complex, but as the genome project began to uncover the instructions for how the “parts” are made there was a feeling that science may be able to build models that describe function and disease.
The 2010 Nature article describes this aspiration:
The hope was that by cataloguing all the interactions in the p53 network, or in a cell, or between a group of cells, then plugging them into a computational model, biologists would glean insights about how biological systems behaved
And indeed this did (and still does) seem like a reasonable approach. Biological networks have turned out to be as complex as we could have hoped. Systems biology is still moving forward, but the sheer number of possible rules that govern how all of the cellular parts work together and interact suggest that we will be working with this complexity for some time. There is a universe of rules that describe networks; explaining how proteins, ligands, nucleic acids and more interact and result in function.
Towards the end of the article there is an interesting quote from Bert Vogelstein:
“Humans are really good at being able to take a bit of knowledge and use it to great advantage,”
And we are. With some careful science and good detective skills we can take what we do know and put it to good use, combating disease. The fact that biological systems are complex and that this complexity is not simply going to be understood the first time we draw back the curtain is a great finding.
I am asking the Tox1401 students to look into this complexity a bit further. Let’s start with a pathway database like reactome.org. Choose the phase II pathways and select a single protein within that pathway, perhaps the NAT1 arylamine N-acetyltransferase. Provide a description of the protein, and the pathway that it takes part in.