When Joël Bloch talks about the beginnings of his passion for biology, it sounds relatively unspectacular. "I think it all started very early," he says. "As a child, I was fascinated by animals, technology and, especially, by dinosaurs." A lot of children now share this passion for these primaeval creatures, but very few of them will, years later, be able to claim that "Research is my greatest hobby." But that is exactly what Joël Bloch says. It all started in cantonal school (gymnasium) in Wattwil, Switzerland, where the teenager's major subjects were chemistry and biology. "Seeing the structure of a protein for the first time was a key experience for me, as I discovered these tiny things were actually unbelievably complex mechanisms catalysing extremely complicated processes." He then knew that his future would be biology.
"The third language of life"
Following studies at the Swiss Federal Institute of Technology and a period of research at the Weizmann Institute in Israel under the chemistry Nobel laureate Ada Yonath, he gained a doctorate in Zurich with his work on sugar molecules that link to proteins in cell membranes. These so-called glycans are something of an "identity card" for the cell type or respective organism. "The blood group is also defined in this manner. Consequently, glycobiology is frequently referred to as the 'third language of life' – in addition to DNA and proteins," says Bloch. N-glycans, the most widely distributed class of glycan, are complex “sugar trees” linked to proteins as “molecular Identity cards”. First, however, these glycans are synthesised gradually through a complex enzyme cascade. During this process, the glycans are linked with fat molecules of the membrane of the cell organelle endoplasmic reticulum.
Bloch succeeded in elucidating the structure of one of these tiny mechanisms, namely an enzyme responsible for the development of this combi-molecule. This tiny mechanism is called ALG6 and belongs to an entire family of so-called glucosyltransferase enzymes. "We were able to draw conclusions with regard to the entire enzyme family and create something of a blueprint regarding the structure of these enzymes and how they function," says Bloch. Together with his co-authors, he also developed a molecular glycan "kit" that enables him to reconstruct and study the entire ALG enzyme cascade in a test tube. This was all basic research in a classical sense, but the discovery could ultimately also affect the production of medicines based on sugar biology, including drugs for organ transplantations, cancer therapies or treatments for viral infections.
Cryogenic electron microscopy is a decisive instrument in researching molecular structures. It had hitherto been practically impossible to shed light on proteins in membranes of cells and cell organelles using this method as they were frequently too small. However, he also managed to achieve a breakthrough in this regard. "We thought it would probably work if we linked an antibody to the protein, thus increasing the weight." During a research period in Chicago, the doctoral candidate Bloch learned how to produce synthetic antibodies and, indeed, it did work.
Today, the postdoc Joël Bloch researches with the chemistry Nobel laureate Roderick MacKinnon at Rockefeller University in New York. In a zoom call, the passionate researcher relates how he loves to explore the city on long walks. His dissertation, on the other hand, was anything but a walk in the park. "Joël's projects were all of a high risk nature, and a lot of experimental difficulties needed to be overcome," says Bloch's doctoral supervisor Kaspar Locher, and his protégé can only confirm this. "It takes a lot of perseverance, and sometimes years go by without any results being achieved. Most things simply did not work." Bloch considered it similar to the first expedition exploring the Antarctic. "You don't know what to expect, or whether you'll get there – and whether you will ever come back again”.
A passion for research is a "priceless gift"
Ultimately, it is exactly this pioneering character that ensures structural biology still remains so "extremely fascinating" for the young scientist. "Aesthetically, it is certainly one of the most attractive sciences," he says with radiant eyes. "If one unravels the structure of a protein, one achieves a beautiful picture, and you are the first person to have ever seen this. And these structures frequently enable one to answer questions that have puzzled biology for decades." Finally, he regards the Prix Schläfli and the lecturing activity associated with it as a sort of obligation to instil other young people with this burning interest in science, "just like my school teacher did with me".
He would like to continue researching in cellular biology "employing techniques that we probably are unaware of today". He dreams of a professorship in Switzerland or the United States, or somewhere "where the setting is just right". Although salaries in industry are very tempting, particularly in the United States, "Being on the front line in science is a priceless gift," he stresses. "Money is no compensation for this."