Salk scientists discover cellular structures with extreme longevity, leading to insights for age-associated diseases
LA JOLLA—(June 6, 2019) Scientists once thought that neurons, or possibly heart cells, were the oldest cells in the body. Now, Salk Institute researchers have discovered that the mouse brain, liver and pancreas contain populations of cells and proteins with extremely long lifespans—some as old as neurons. The findings, demonstrating “age mosaicism,” were published in Cell Metabolism on June 6, 2019. The team’s methods could be applied to nearly any tissue in the body to provide valuable information about lifelong function of non-dividing cells and how cells lose control over the quality and integrity of proteins and important cell structures during aging.
“We were quite surprised to find cellular structures that are essentially as old as the organism they reside in,” says Salk Vice President, Chief Science Officer Martin Hetzer, senior author and professor. “This suggests even greater cellular complexity than we previously imagined and has intriguing implications for how we think about the aging of organs, such as the brain, heart and pancreas.”
The Pilhofer lab will investigate macromolecular machines mediating cell-cell interactions across different scales of resolution. Cryo-electron tomography will play a key role in imaging these systems in their cellular context and in a native state, enabling integration of data from other research disciplines. The development of cutting-edge cryo-EM methods will keep ETH at the forefront of structural biology and enable us to better understand diseases and develop new drugs to treat diseases.
Pilhofer received a PhD from the Institute of Microbiology, Technical University of Munich, Germany, in 2008. Following his studies, he was a Postdoc at the California Institute of Technology (Caltech) and the Howard Hughes Medical Institute (HHMI) until 2013. He is the recipient of the EMBO Young Investigator Award and a European Research Council Starting Grant.
Funded by the NOMIS Foundation, in cooperation with the Monique Dornonville de la Cour Foundation, the cryo-EM professorship is associated with the Institute of Molecular Biology and Biophysics in the Department of Biology at ETH. The role is integrated into the research activities of the department and encourages new collaborations and interdisciplinary projects. In particular, the professorship strengthens the link between structural biology and the fields of biochemistry, molecular health sciences, infection biology and systems biology.
On April 10, 2019, the Salk Institute celebrated the 10th anniversary of the NOMIS Center for Immunobiology and Microbial Pathogenesis. The anniversary symposium, titled “The Power Within – Harnessing Our Immune System for Better Health,” brought together experts in immunology, virology, and infectious diseases and showcased the contributions of scientists who have made a significant impact in the study of infections and contagious diseases. The event, with talks for both scientists and lay audiences, drew members of the community, scientific leaders, philanthropists and others. A keynote presentation by investigative journalist and author of “Pandemic: Tracking Contagions, from Cholera to Ebola and Beyond” Sonia Shah, capped the event.
Doctors have long observed that biological age and chronological age are not always one and the same. A 55-year-old may exhibit many signs of old age and have numerous age-related diseases, whereas an 80-year-old may be healthy and robust. While diet, physical activity and other factors play a role, there are many contributors as to why and how some people age better than others. Those contributors remain poorly understood.
For a study published December 19, 2018 in Genome Biology, a collaborative team at the Salk Institute analyzed skin cells ranging from the very young to the very old and looked for molecular signatures that can be predictive of age. Developing a better understanding of the biological processes of aging could eventually help to address health conditions that are more common in old age, such as heart disease and dementia.
“This experiment was designed to determine whether there are molecular signatures of aging across the entire range of the human life span,” says co-senior author Saket Navlakha, an assistant professor in Salk’s Integrative Biology Laboratory. “We want to develop algorithms that can predict healthy aging and nonhealthy aging, and try to find the differences.”
“The study provides a foundation for quantitatively addressing unresolved questions in human aging, such as the rate of aging during times of stress,” says Professor Martin Hetzer, co-senior author, as well as Salk’s vice president and chief science officer.
Personalized medicine is changing the way clinicians approach diagnosis and treatment by tailoring therapy to individual molecular and genetic profiles. While the idea of tailored medical treatment is not new, this medical model is rapidly evolving as new technologies are developed.
Jacob Corn, Professor of Genome Biology at ETH Zurich, is working to advance personalized medicine by exploring processes that detect and repair damage to DNA and using these findings to repair, switch on or off, or replace genes in the genome at a defined position. Through the professorship, the Swiss science and technology university is participating in an effort to establish and advance the field of personalized health and technology via a national initiative. The professorship — a partnership with ETH, in cooperation with the Lotte und Adolf Hotz-Sprenger Stiftung — is enabling the study of the functional elements encoded in complex genomes through comparative analysis, seeking to deepen our understanding of how genetic variation in the human population is related to disease susceptibility.
Ruben Garcia Santos of the NOMIS Foundation (NOMIS) sat down to talk to Corn (JC) about his new role at ETH, his switch from industry to academia, his research goals and the future of genomics, a growing field that is gaining tremendous public attention.
NOMIS: Welcome to Zurich! You moved your family and your lab to Switzerland and have been on the job for a few weeks now. How are you finding the new location and research environment?
JC: Zurich is great! It’s the perfect combination of city, culture and outdoors. ETH has also been outstanding. Everyone is very welcoming and the scientific atmosphere is incredibly stimulating. I’ve had so many wonderful conversations about possible collaborations in a very short amount of time. The possibilities are very exciting.
NOMIS: What inspired you to join ETH?
JC: My wife and I had lived in the San Francisco Bay Area for almost two decades and were looking to shake things up. It was important to us that our new home offer just as much in terms of scientific excellence, a progressive social environment and access to nature and the outdoors. We looked at many places, but Zurich was an incredible blend of everything. Also very important to me was the public nature of ETH. In the United States there can be a big difference in resources available to public versus private universities. But I believe that outstanding education is a natural right for everyone, not just those who can afford it. ETH offers the best of both worlds: world-class facilities and resources for research, paired with equal access. I am still amazed at the incredible things students have access to at ETH!
NOMIS: What do you hope to achieve through your professorship at ETH?
JC: Genome editing is already changing biological research. It has spread very quickly and I hope to further increase access to this exciting technology to other groups. This will let them answer their own research questions at speed, without bottlenecks. Of course, genome editing also shows a great deal of promise for the treatment of genetic diseases. I am committed to helping doctors learn more about what genome editing might be able to do for their patients, and to work with them in advancing genome editing tools toward the clinic. Some diseases are getting close to possible therapies, while others are still very far away. There is still much to be done!
NOMIS: You are no stranger to working in multidisciplinary teams or leading transdisciplinary research projects in academia and in industry. What lessons have you learned in terms of challenges and critical success factors in collaborative research that could be applied to this innovative, interdisciplinary endeavor at ETH?
JC: Diversity and trust are key in any environment, but especially in science. Diversity yields different opinions, different expertise and different life-views. Putting these differences together leads to creativity and exciting solutions to difficult problems. But with diversity, one must be able to trust that you can share your thoughts; they may be quite different from those of your colleagues. It’s important that we can trust each other to listen and consider one another’s opinions carefully, and receive constructive feedback in a way that not only makes us more confident but also more productive. My research is most exciting when it’s filled with many different kinds of scientists, who talk openly among each other to solve difficult problems. It’s the same in research as in life.
NOMIS: You began your career in academia, moved to industry, then returned to academia in 2010. What was it that brought you back to academia?
JC: I loved my time in industry for several reasons. I felt a strong connection to patients, whom my research was trying to help. The concreteness of the research was very appealing. But when next-generation genome editing was starting to be developed, I was given a very special opportunity by Jennifer Doudna at UC Berkeley to be part of a scientific revolution and start an academic institute. These opportunities don’t come around very often! It was clear to me that genome editing was going to completely revolutionize research and also the treatment of genetic diseases. We are at the edge of incredible breakthroughs. Someday genetic disorders that have been with humankind for millennia may be as easily treated as a broken bone. But this is not guaranteed, and there is still a lot of very important and difficult research to be done.
NOMIS: Where do you expect to see the greatest advancement in our understanding of the fundamental mechanisms of genetic diseases and their treatment in the next years?
JC: Personalized medicine is advancing to the point where patients can now have their genome sequenced. This still does not happen very often, but the future is clear. But what happens after the genome is sequenced? If you see a problem, how do you do something about it? Very rapid and personalized genome editing could address this problem by creating personalized treatments for individual genomes. But there are many issues to be ironed out, such as proving safety for each treatment, figuring out medical manufacturing for a treatment that will only be used by one person and so on. As I keep saying, these are exciting times with still a lot to do!
eikones has announced four new NOMIS Postdoctoral Fellowship recipients for 2018-2019: Zeynep Gürsel, Sean Silver, Philipp Ekardt and Tobias Wilke. eikones — Center for the Theory and History of the Image at the University of Basel is dedicated to the interdisciplinary study of images as instruments of human knowledge and cultural practice. The fellowships support groundbreaking research in the interdisciplinary field of image studies, specifically concerning the function of images as models in epistemic, aesthetic and didactic contexts.
Zeynep Devrim Gürsel is a media anthropologist and associate professor in the Department of Anthropology at Rutgers, the State University of New Jersey. She completed her PhD in anthropology with a designated emphasis in film studies from the University of California, Berkeley in 2007. Her scholarship involves both the analysis and production of images. She is the author of Image Brokers: Visualizing World News in the Age of Digital Circulation (University of California Press, 2016), an ethnography of the international photojournalism industry during its digitalization at the beginning of the 21st century. She is also the director of Coffee Futures, an award-winning ethnographic film that explores contemporary Turkish politics through the prism of the everyday practice of coffee fortune-telling. As a NOMIS Fellow at eikones she will be working on Portraits of Unbelonging, the first in-depth exploration of the official role of photography in the history of Armenian emigration to the United States.
Sean Silver completed his PhD in 2008 at the University of California, Los Angeles and is now associate professor of literature at Rutgers, the State University of New Jersey. He has written widely on the literature, philosophy and sciences of 17th and 18th century Britain. He is author of The Mind Is a Collection, an award-winning exhibit catalogue and virtual museum of objects used to model cognitive processes in 17th and 18th century Britain and Europe. As a NOMIS Fellow at eikones he will be studying complexity in the 17th and 18th century arts, a project blending computer-aided network modeling with readings of early-modern philosophical and literary texts.
Philipp Ekardt has held teaching and research positions at the Peter Szondi-Institute for Comparative Literature at Freie Universität Berlin, he was a member of the Bilderfahrzeuge project at the University of London’s Warburg Institute, and served as editor-in-chief of the journal Texte zur Kunst. His first monograph Toward Fewer Images: The Work of Alexander Kluge, partly based on his PhD dissertation at Yale University, has been published as an OCTOBER Book with MIT Press. He is currently completing his second book — to appear with Bloomsbury Academic — which reconstructs Walter Benjamin’s fashion theory, tracing its implications and manifest relations with the fashion criticism of its moment and the history of Paris couture, attending to its connections with sociological and morphological theories, proposing a reevaluation of the term elegance as an aesthetic concept, while also investigating the subject of fashion as an epistemic object that allowed Benjamin to reconsider fundamental questions such as time and material. As a NOMIS Fellow at eikones he will be working on Assemblages and Compositions: Image Models in Goethe and Lady Hamilton, looking at the writings of Goethe and the art of attitudes performed by Lady Hamilton to investigate a historical formation, as well as an entirely different epistemic model, in which a surprisingly different logic for the configuration of movement, gesture and image is encountered.
Tobias Wilke is a literary and media historian. He completed a binational doctorate (co-tutelle) at Princeton University (PhD) and the University of Tübingen (Dr.phil.) in 2008. Subsequently, he was postdoctoral fellow (2008-2009) and project leader (2009-2012) in the research cluster “Languages of Emotion” at the Freie Universität Berlin, as well as assistant professor of German literature at Columbia University, New York (2009-2018). His research focuses on the literature of European modernism, the history of media and media theory from the 19th through the 21st centuries, intersections between literary history and the history of science, the history of emotions, and sound studies. He is the author of Medien der Unmittelbarkeit: Dingkonzepte und Wahrnehmungstechniken 1918-1939 (Wilhelm Fink, 2010) and Einführung in die Literatur der Jahrhundertwende (Wissenschaftliche Buchgesellschaft, 3rd ed. 2016; together with Dorothee Kimmich), and editor of several other books. As a NOMIS fellow, he will be completing a book titled Sound Writing: Experimental Modernism and the Poetics of Speech, examining the history of the notion of linguistic “articulation” at the intersection of graphic recording technologies, scientific cultures of experimentation and poetic practices of the avant-garde, ca. 1870-1970.