Salk: “Age is more than just a number: machine learning may be able to predict if you’re in for a healthy old age”

From left: Martin Hetzer, Swati Tyagi, Roberta Schulte, Hsiao Tsai, Saket Navlakha, and Jason Fleischer (photo: Salk Institute)

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.

Hetzer is leading the Determining Biological Age in Humans project at the Salk Institute and is a member of the NOMIS Board of Directors.

Advancing personalized health: an interview with Jacob Corn

Jacob Corn (photo: ETH Zurich)

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!

ETH Zurich

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 announces four new NOMIS fellows

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.

ETH Zurich: “Insight into the world of designer DNA drugs”

The ETH Zurich Foundation has published an article highlighting NOMIS Distinguished Scientist Don W. Cleveland’s lecture at ETH Zurich on Oct. 3, 2018. The talk, which was part of the NOMIS event celebrating the 2018 Distinguished Scientist awardees, addressed aspects of Cleveland’s work, including his gene-silencing therapies, also known as designer DNA drugs, which can block the activity of the gene whose mutation causes neurodegenerative diseases such as Huntington’s or Alzheimer’s disease.

The NOMIS Distinguished Scientist Award is enabling Cleveland and his team to identify a previously unknown mechanism for cell entry in the mammalian nervous system, develop gene editing/gene suppression approaches, and identify the underlying basis for liquid-liquid de-mixing and its contribution to neurodegenerative disease.

The ETH story also highlights other partnerships between NOMIS and ETH, including the Professorship of Genome Biology, to which Jacob Corn has been appointed, and the Professorship of Cryo-Electron Microscopy, which is held by Martin Pilhofer.

A German version of the article has also been published: “Einblick in die Welt der Designer DNA drugs.”

Salk: “Tweaking cells’ gatekeepers could lead to new way to fight cancer”

NOMIS scientist Martin Hetzer and other Salk Institute researchers have devised a way to manipulate numbers of individual nuclear pores — a breakthrough that may one day stop cancerous cells from proliferating out of control. The finding was published in an article in the journal Genes & Development.

Nuclear pores are essential elements of all cells that provide controlled ways to move cellular material in and out of a nucleus. In organisms ranging from fungi to mammals, individual cells possess these transport channels that mediate a thousand events per second. Individual nuclear pores are fashioned from multiple copies of 30 proteins known as nucleoporins. Hetzer and colleagues looked at the nucleoporin Tpr, which has been implicated in certain cancers.

The team showed that each of the transport channels within a cell is unique, and each cell nucleus possesses a specific number of nuclear pores. Next, the team used molecular methods to remove Tpr to see its effect on the number of nuclear pores, with a surprising result. Cells with the Tpr protein have fewer nuclear pores than cells without the protein. Typically, removing proteins in the nuclear pore complex results in a reduction of nuclear pores. This indicates that Tpr plays a role not in transport itself, but in regulating the assembly of nuclear pores. These new insights could be crucial for future attempts to manipulate numbers of nuclear pores to treat disease.

Hetzer is Salk’s vice president and chief science officer, as well as a NOMIS board member. The Salk Institute has been a NOMIS partner since 2008.

Photo: Salk Institute

ETH: “A new era in biomedicine”

ETH Zurich has announced that it has obtained a new state-of-the-art cryo-electron microscopy device, is modernizing its existing equipment, and has established the Professorship of Cryo-Electron Microscopy, which will enable the leading Swiss science and technology university to further develop in the area of biomedical research.

Proteins play a central role in almost all biological processes. They are often very sensitive compounds, continually changing their form in cells, and cannot be examined using a conventional electron microscope without causing changes in the structure that affect the validity of the measurements. The development of the cryo-electron microscope is thus a huge breakthrough for biochemical and medical research. The technology enables proteins to be examined in their actual form down to the atomic structure, thereby allowing their mechanism of action to be better understood. Cryo-electron microscopy can be combined with other methods to more closely examine how processes in healthy and sick cells differ from one another.

To enable researchers at ETH to pursue biomedical insights, the NOMIS Foundation is funding the professorship in cooperation with the Monique Dornonville de la Cour Foundation and other private donors.