How is life constructed? This is the question U of T professor Mike Tyers of the department of medical genetics and microbiology is attempting to answer by unraveling the mysteries of cellular biology. He’s using an unconventional approach: proteomics.
For centuries, biological reductionists have studied one particular gene, the unit of heredity, or the molecule encoded by a gene, which is only a single protein. Tyers takes a holistic scientific approach by focusing on the genome, the entire set of genes in a living system, and the proteome, the myriad of proteins an organism needs throughout its life.
“Looking at the global properties of biological networks [gives you the] perspective of being able to look at every gene or protein function in the cell,” explained Tyers. “Conventional genetics is limited in that it only gives you an idea of the tips of the genetic landscape.”
Proteins and genes rarely carry out biological processes on their own, but rather overlap with other processes, forming a network of interactions in order to coordinate a single function within a cell.
Unraveling all the protein interactions in a living system is particularly challenging since proteins, unlike genes, are dynamic and change when encountering different molecules in their environment. When looking at whole organisms, the study of the proteome gets even more complex as certain areas have different concentrations of proteins depending on age and outside environment.
Mapping global biological networks may have significant medical applications, particularly in the area of drug development.
“The concept behind drug discovery in pharmaceutical research is based on finding the ‘perfect’ drug, one compound that has perfect specificity and does exactly what you want it to do. This doesn’t exist in biology,” said Tyers. Often, diseases are caused by multiple mutations in a number of genes, so a drug that corrects for only one of these mutations is not effective.
Tyers is approaching this problem by screening the effects of various chemicals on the entire genome. Each chemical will cause-not fix-a specific mutation in a gene that contributes to a particular disease. This will allow Tyers to map a ‘chemical network’ of mutations involved in a single disease.
“We call this the ‘Magic Shotgun’ approach. We’re looking for a magic shotgun, a combination of compounds that create mutations which are all contributing to a particular disease,” explained Tyers. This research will aid the development of more effective drugs for complex diseases.
Despite the possibilities proteome research offers, the field is still in its infancy where research tools and techniques are involved.
“The technology platform is still in [its] very early stages [of development]. It’s not even possible to take a snapshot of the protein interaction network, so we can’t follow hundreds of thousands of protein interactions dynamically in an experiment at this point.”
One critical piece of technology in proteomics is mass spectrophotometry, an ultra-sensitive analytical method that can identify unknown proteins. This technology has allowed Tyers to carry out the first systematic proteomic study published in 2002, which provided the first glimpse into the global properties of protein networks.
“People are still underestimating how complicated life is. We cannot claim to understand a biological system that has 50 genes in it, let alone [that of] humans, which have 20,000 genes,” said Tyers.
