Ahead of our 1st WIA Annual Symposium, we had the pleasure to get in touch with our keynote speakers. They will, no doubt, give yet another remarkable presentation of their work on the 30th of November, but we wanted to know more about them. What motivated them, what inspired them to be where and who they are now? How can young female scientists follow in their footsteps?
Prof. Daniel Klionsky, to many known as the person who discovered the famous Cvt, or cytoplasm-to- vacuole pathway, in yeast, shares his insights into the field, provides us with a bit of background as to how he found himself working on autophagy, and outlines why our WIA network is important for the continuous expansion of the field.
Q: What attracted you to the field of autophagy?
Prof Daniel Klionsky: Initially, I had no interest in macroautophagy/autophagy. As a postdoctoral fellow in Scott Emr’s lab, I was interested in protein targeting to the yeast vacuole. When I started my own lab, one of the projects I initiated was an analysis of the vacuolar targeting of the resident hydrolase aminopeptidase I. Thus, I was working on biosynthesis, not degradation. However, once we identified mutants in the pathway, we found out that there was almost a complete overlap between the cytoplasm-to-vacuole targeting pathway and autophagy. No one at that time thought that autophagy would turn out to be such an important pathway, as there was relatively little interest in the vacuole or macromolecular degradation.
Once we started to learn more about the mechanism, I became interested for at least two reasons. First, autophagy involves dynamic membrane rearrangements, various protein- protein and protein-membrane interactions, and delivery of proteins to an organelle, topics which are similar to my general interest in protein trafficking. Second, autophagy represented an entire pathway involving several proteins (when the molecular components were first being identified, we had no idea how many there would be), and none of them had been characterized—I always favored the idea of working on multiple proteins, rather than focusing on one. The breakthrough in identifying the autophagy-related proteins occurred shortly after the yeast genome was sequenced. Thus, considering the tremendous amount of genome-level sequencing that has occurred since then, autophagy may represent the last extensive pathway that remains to be discovered at the molecular level.
Q: What do you consider to be the most exciting recent discovery in autophagy?
DK: The structural studies on Atg2-Atg9 that are providing insight into the mechanism of lipid mobilization during autophagy. Combined with the work on membrane contact sites, we are starting to get a better idea of how the phagophore is nucleated and expands.
Q: What is the career achievement you are most proud of?
DK: The discovery of the cytoplasm-to-vacuole targeting pathway. First, this represents the best- characterized example of selective autophagy. Along these lines, we identified the first ligand, receptor and scaffold that participate in a selective type of autophagy, establishing what has turned out to be a paradigm for the selective mechanism. Second, our entry into autophagy via this pathway was completely independent of work carried out in other labs.
Q: Why do you think networks like WIA are beneficial?
DK: It is somewhat distressing to me to contemplate how far we (the USA, the world) still have to go with regard to achieving equality for women. Consider that in the USA, it has taken almost 250 years to finally elect a woman to one of the top two positions in our government. In some ways, biology has provided more opportunities for women than other fields. However, even in this field many biases remain. Sadly, scientists are as guilty, or more so, in this regard; as scientists, we think we know better than to be subject to ingrained attitudes about women, which tends to make us unwittingly subject to the very biases we are so sure we are avoiding (note that women are as guilty of these preconceptions about other women as are men). Thus, having a venue that provides additional support for women in science, in this case women in autophagy, offering an opportunity for additional mentoring, networking and experience in organizing scientific activities, has obvious benefits.
Cell biologist Daniel J. Klionsky, Ph.D., is the Alexander G. Ruthven Professor of Life Sciences at the University of Michigan. Dr. Klionsky received an A.B. in Biology from the University of California, Los Angeles in 1980. He received his Ph.D. from Stanford University in 1986, which was followed by Helen Hay Whitney and American Cancer Society Senior Postdoctoral Fellowships at the California Institute of Technology. In 1990, Dr. Klionsky joined the faculty of the University of California, Davis. He moved to the University of Michigan in 2000. Dr. Klionsky was elected a Fellow of the American Association for the Advancement of Science in 2009, was named a Thompson Reuters Citation Laureate in 2013, was awarded the van Deenen Medal from the University of Utrecht in 2015, and was elected to the American Academy of Arts & Sciences in 2019. Since the journal’s founding in 2005, Dr. Klionsky has also served as the editor-in-chief of Autophagy.
Interview by: Andrea Gubas, Anna Scotto Rosato, Roxana Resnik, and Carmen Figueras-Novoa