Photo courtesy of Embassy of Sweden, Washington
The nervous system of the human body is vast and labyrinthine. Nerve cells (called neurons), and the various other types of cells that support them, extend throughout the body. Signals from these cells can sometimes traverse our bodies internal machinery at speeds of up to 120 metres per second, just to perform acts as simple as tapping a foot. Our modern understanding of biology places this complex network at the centre of what we think of as our “self”. That is to say, this enormous interconnecting mesh of microscopic cells comprises everything we are as people. The entire nervous system; the brain, the spinal cord, the nerves in our fingertips that give us our sense of touch and all the cells that connect them, are types of neurons. Our understanding of this vast network was, until recently however, woefully inadequate.
Trying to map out the paths taken by neurons, the main messenger carriers in our bodies, is not an easy task. If it were, we would have completely modelled a brain by now. There is still much that we don’t know. Instead, we have to be content with little victories which, in recent years, have contributed greatly to our overall understanding of how this complex bodily function operates.
One such victory was the discovery of how the neurons in our body actually transmit their messages between one another. The steps that govern this fundamental part of our bodies function have taken years to uncover. It’s hard to believe that it’s only in recent years that this mechanism was finally unearthed. It turns out that the process of neuronal cell signalling (called synaptic transmission) is caused by bio-electrical signal at the bottom of the neuron. This causes Calcium ions to flood the base of the neuron and this, in turn, initiates the release of neurotransmitters which cause the same process to be repeated in the following neuron.
So important was this discovery that the 2013 Nobel Prize in Physiology or Medicine was awarded to the three scientists credited with discovering it. The recipients were James E. Rothman, Randy W. Schekman and Thomas C. Südhof.
One of the trio, Professor Thomas Südhof , was in DCU to give a public lecture address at NSI’s recent conference. The University Observer was lucky enough to get an opportunity to speak with the man about his life and work.
For those unfamiliar with the finer points of his research, Professor Südhof’s work focuses on the events within the presynaptic neuron that lead to the release of neurotransmitters.
“My contribution to this problem was to contribute to the understanding of membrane fusion to, I think, solve the question of how membrane fusion is controlled by calcium entering the synapse and to generate a framework of understanding how the presynaptic release machinery is assembled via scaffolding proteins that also recruit calcium channels and, in a nutshell, that is what the Nobel Prize was for,” Professor Südhof says.
To put that in layman’s terms, electrical signals travel through neurons and when they reach the synapse (the gap between one neuron and the next) these signals trigger calcium channels to open, allowing calcium ions to enter the neuron and kickstart the release of neurotransmitters. At the synapse, neurotransmitters are found in enclosed sacs called vesicles. The synapse itself is separated from the neuron by the cells plasma membrane, so in order for neurotransmitters to be released into the synapse, they must escape from their vesicles and cross that barrier. This is no simple task. To do this, the membranes of the vesicles must fuse with the plasma membrane. The vesicle membrane then becomes a part of the plasma membrane, releasing the neurotransmitters into the synaptic cleft. Think of it almost like a bubble of air rising to the surface of a pool and releasing the air it contains to the outside world.
Within neurons – and within cells in general – cell structures are not just free-floating throughout the entirety of the cell. The location and movement of cellular structures is carefully and precisely maintained by other components of cell machinery. A series of events must therefore occur to move a neurotransmitter-filled vesicle to the plasma membrane of the synapse, and to then allow the vesicle to become tethered to the membrane, fuse with it and release its contents. The events that ultimately lead to the membrane fusion are triggered by the influx of calcium ions into the synapse. Professor Südhof discovered how calcium ions cause this effect when he found the protein known as Synaptotagmin. It was this discovery that led to his inclusion in the Nobel Prize.
The action of Synaptotagmin is similar to other processes found within the human body. The protein is found at the synapse, attached to inner wall of the plasma membrane. It is sensitive to levels of calcium ions and interacts with SNARE proteins (Soluble NSF Attachment Protein Receptor). SNARE proteins are found on the vesicles that contain neurotransmitters and on the target membrane and so are called v-SNAREs (for the vesicles) or t-SNARES (for the targets) accordingly. When calcium ions enter the synapse, synaptotagmin causes the v-SNAREs and t-SNAREs to bind together and form a SNARE complex. The formation of this complex is what causes the membrane fusion necessary for neurotransmitter release. In Professor Südhof’s own words:
“It’s actually very difficult to explain what one discovered because understanding a process such as neurotransmission requires literally thousands of individual discoveries. So I wouldn’t credit myself with discovering any particular one thing. But my work led to the identification and subsequent classification of the number of molecules that are essential to synaptic transmission including synaptotagmins.”
Since there are no major diseases associated with defects in this particular biological pathway, one might question the importance of his research, as it doesn’t immediately have an obvious benefit to human health.
However, this process is key in allowing synaptic transmission to occur and, according to Professor Südhof, “synaptic transmission is the fundamental process by which neurons in the brain communicate with each other and everything the brain does, absolutely everything, depends on that communication.”
It’s easy to see his point. Understanding how our body communicates with itself on the most fundamental of levels can only be considered a good thing.
As for how he ended up where he is today, Professor Südhof studied medicine at university, and went on to earn a PhD and do some post-doctoral research. He decided to pursue a career in research rather than in clinical medicine, describing the choice as having been made:
“…relatively late, after I had finished my post-doc and the choice was to either head my own lab or go back to clinical medicine and at that point I decided to start my own lab instead.”
The choice he made would ultimately result with him being awarded the Nobel Prize, so few can say he made the wrong one. His decision shows that one does not have to have everything figured out early on in one’s life to be successful, a fact that will surely please many a disillusioned student at a loss as to what to do with their degree.
Professor Südhof places emphasis on the “flexibility” of medical training when he studied in college, as then “it was possible to have a reasonable education in science” from the medicine programme, whereas, in his opinion, “medical training today has become much more practical and less scientific.” He also highlights the importance of this flexibility in allowing him to pursue a research career. When asked his favourite part of being a scientist, Professor Südhof is quick to answer: “My favourite thing about being a scientist is to understand something to work on something and to come up with an idea that explains how it works.”
The professor plays a role in education and has a responsibility to do so, particularly given his receipt of the Nobel Prize. One would imagine that someone in his position, particularly given his passion for science, would place great emphasis on the learning of STEM (Science, Technology, Engineering and Mathematics) subjects from an early age, but Professor Südhof has huge regard the arts and firmly believes children should be learning arts subjects at young ages and not focus on learning STEM subjects until they are older.
“I think that, in general, as children grow up it may not be very important to train them in math and science but it is very important when they are young to train them in things like language and art, including music. It is important to educate children in STEM subjects, Science, Technology, Engineering, Mathematics, when they get older however when children get older in their late teens they’re no longer children obviously… their ability to learn STEM subjects is very good but their ability to learn arts subjects like language goes downhill.”
This opinion comes from his own experiences, as Professor Südhof learned bassoon as a young child, saying “My own personal development was tremendously shaped by learning music at a relatively early age.” Likewise, he uses his German background as evidence for the importance of learning languages at a young age. “The fact that I have an accent in English even though I first came to the States when I was sixteen shows you that how difficult it is to learn a new language after a certain age.”
Despite having strong opinions regarding the ideal education system, Professor Südhof no longer does “much classroom teaching”. The majority of his work as an educator is spent with graduate students and post-doctoral researchers in his lab at Stanford University. The work for which he was awarded the Nobel Prize involved vesicular trafficking, the movement of vesicles within a cell, a topic which would be typically classified as a “cell biology question” but he is quick to maintain that his profession is that of a cell biologist.
“I do not consider myself a cell biologist, I consider myself a neuroscientist because I’m really interested in trying to understand how neurons in the brain communicate with each other at synapses.”
Professor Südhof acknowledges that being awarded the Nobel Prize has changed his career. He is certainly a lot busier now but overall sees his position as a Nobel Laureate as “a positive experience as it’s very nice to be recognised, and very flattering.” As a Nobel Laureate he has been the given the opportunity but also a responsibility to talk about “things that I feel are important and neglected… the place of science in society and the purpose of science.” He speaks of the public discussion of science and how science is portrayed within society, declaring that “the value of (science) has to be seen exclusively based on whether or not the content is true, not based on whether or not somebody likes it or whether it’s applicable… I think that science in an incredibly important and incredible way is an asset to society.”
When asked for advice for young scientists, Professor Südhof’s response seemed applicable to all students, all young people, and indeed all people in general, and echoes the choices he has made in his career. “Follow your interests. It’s very simple. Don’t do things that you’re not really interested in and that you don’t really like, because life is short.”