On October 7, 2013, in Stockholm, Sweden, the Nobel Committee announced the winners of the Nobel Prize for Medicine and Physiology – two Americans and one German, all now located at institutions in the US. The discovery for which these three investigators share the prize involves their work over three decades studying the transport, packaging and trafficking of cellular proteins.
All cells must communicate and maintain their identity. To do so cells have developed intricate systems whereby neurotransmitters, proteins, hormones, and other species are encapsulated in small vesicles. These vesicles may be utilized to extrude materials into the extracellular domain or may store materials within the cell for later use. Working in model systems including yeast cells, these investigators showed the intricacy of cellular physiology associated with micro-vesicular function.
What makes these investigators’ work so interesting is that it is principally the study of cellular physiology, or what we call cell biology. While many breakthroughs and observations today reflect discoveries at the level of DNA, RNA and the genome, these investigators have pioneered protein kinetics and physiology. What is so exciting about this Nobel Prize is that it returns attention to the intricacies of cellular function at the level of phenotype. Protein biology represents the final common pathway from blueprint (DNA) to function. While genes that are detected within the nucleus (the purview of genomic analyses and many recent Nobel prizes) may or may not ultimately be expressed, depending upon splice variants, DNA methylation, histone acetylation, small interfering RNAs and non-coding DNAs among other phenomena, functional proteins are the active end-product and do very much exist.
We now recognize that cellular signaling, misfolded protein response, autophagy and apoptotic responses are tightly bound together. Among the most toxic phenomena for a cell is the misfolded protein signal, a signal that occurs far from the gene. This represents the target of the newest classes of drugs known as proteasome inhibitors and heat shock protein inhibitors, which function within the cytoplasm, not the nucleus.
It is exciting to imagine a day when physiologist, biochemist, enzymologist, physical chemist, and protein chemist regain their position as leaders in cancer research.
N.B: It should not go unmentioned that the assay offered by Rational Therapeutics is based on cellular function.
Robert A. Nagourney, M.D.