Research Spotlight on Nobel Laureate Thomas C. Südhof
For those interested in scientific research, the Nobel Prize is an esteemed award, recognizing one’s work and dedication. However, many student researchers are often disillusioned about the kind of work that is put in to receive such high praise. More often than not, these individuals did not suddenly discover something new. To be sure, their findings are the fruits of years of research and passion in the field of science. As a great model of dedication, recent Nobel laureate Thomas Südhof provided incredible insight to our understanding of the human brain communication. But, once again, his work was in the basic-science field, on a topic which, in fact, we learn about in our introductory neuroscience courses. In this brief article, I will outline the most recent findings from Dr. Südhof’s lab in hopes of showing aspiring researchers that continued diligence and passion for learning is most important.
Neurons communicate with each other by a signaling process mediated by what is known as action potentials. Changes in concentration and electrical gradients cause the action potentials to fire down the neuron, until it reaches the synaptic bouton. It is here that one neuron forms a synapse with another neuron. The synapse is the site at which communication is happening. But, for the most part, two neurons are not physically connected, so how does communication happen? In a process called neurotransmission, when the action potential reaches the end of the neuron, an influx of Ca2+ ions cause vesicles to release certain chemicals out of the neuron, as a signal to the next. These vesicles are like little packets of neurotransmitter chemicals. Herein lies the question that Dr. Südhof sought to illuminate: mechanistically, how do these vesicles actually release the chemicals?
Over years of research, Dr. Südhof and many scientists began to shed light upon how the neurotransmitters were being released. Specifically, a group of proteins called SNAREs (SNAP receptor proteins) were identified as important. These proteins, which are present on the vesicular packets of neurotransmitters and also on the membrane of the synaptic bouton, can interact with each other in a clamp-like fashion. This interaction brings the vesicles close to the membrane, and leads to release of the chemicals as the vesicles fuse via endocytosis. Previously, this fusion event was thought to be through a zipper-like method where, as the vesicles get close, they form a pore opening through which the chemicals are released.
This process of neurotransmission and vesicle fusion is a topic that is taught in introductory neuroscience courses. So it must be a model set in stone, right? Actually, a very recent paper by Dr. Südhof and his lab brought forth some new findings that are contradictory to the present model. The paper can be found published in Neuron. Without going into excessive detail, Dr. Südhof’s lab learned that a certain region of SNARE protein domains (the transmembrane region or TMR) was not actually essential for the protein function. At first, this doesn’t seem so important. But then, consider the amount of in vitro research done by other scientists who have found these TMR domains of the SNARE proteins to be important for vesicle docking and fusion. This seems to be intuitive because, as we know, the SNARE proteins are trying to get the vesicles to actually fuse to the plasma membrane so that they can release their contents. Indeed, the present model suggests that the TMR domains actually cause the plasma membrane to physically change in order to accommodate vesicle docking.
What Dr. Südhof’s lab did was look at the SNARE proteins in detail, surprisingly, for the first time in in vivo neurons to examine the importance of the TMR region in a physiological environment. Ultimately, they took out the TMR regions and replaced it with a non-specific anchor for the SNARE protein syntaxin. Despite the belief that the TMR regions are essential for fusion, Dr. Südhof found that, even without the TMR regions, neurotransmission and vesicle fusion was normal. This is a seemingly small, but shocking finding on a topic that every college neuroscience student has been lectured on.
Before this becomes a long piece on pure science, what I wanted to show here was the fact that Dr. Südhof’s work doesn’t necessarily promise to change the world of medicine and science. But his basic science research about an often overlooked topic of neurotransmission, eventually led to great understanding of the process of neural signaling. More so, after elucidating the SNARE model for vesicular fusion several years ago, he continued to work to truly understand this mechanism, culminating in his recent paper and recognition through the Nobel Prize in Physiology or Medicine.
With such important implications in developmental and neural processes of signaling, Dr. Südhof’s work is truly incredible in the scope of human understanding of the brain. But what’s interesting for aspiring researchers is that his work was incremental and, on the surface, not world-shattering. In an interview back in September by the Stanford University School of Medicine, when he was asked to recall any eureka moments that catapulted his hunches, Dr. Südhof said that “Science advances step by step, not in jumps. I believe strongly that most work is incremental…requires a long view, and plenty of patience.” The idea that researchers need to focus on work that promises findings that will change the field is ridiculous. The whole point of scientific research is based on questioning how things work—so would it be possible to determine which research is more important? Even non-clinical, basic-science research, like that of Dr. Südhof, has great implications on the field of medicine. As researchers, we should be more focused on topics of interest to ourselves, and diligent work to elucidate that research, and be less focused on the worries of getting important findings to get top-notch publications.
-Anthony (Byung Kyu) Jun
Thomas Südhof wins Nobel Prize in Physiology or Medicine – Standford News