Professor Gunnar von Heijne and his multifaceted scientific journey

Gunnar von Heijne is a professor of theoretical chemistry at Stockholm University and an esteemed member of the Twin4Promis Scientific Advisory Board. He started his career with a foot in both journalism and research. Following a postdoctoral stint in the USA, he spent three years balancing his time between research and working as a part-time scientific correspondent for Swedish National Radio. Eventually, his passion for research surpassed his desire to communicate science. As he puts it, “scientific articles have a much longer lifespan than a radio program.”

Professor Gunnar von Heijne’s research career has been distinguished by significant roles, as noted in his CV. From 2016 to 2021, he directed the National Cryo-EM Center at SciLifeLab, Sweden’s premier institute for molecular biosciences, while also holding a professorship at Stockholm University. His research has earned numerous awards and honors, and he is an elected member of the Royal Swedish Academy of Sciences, the Academia Europaea, and the Royal Swedish Academy of Engineering Sciences.

Beyond his research commitments, Professor von Heijne served on the Nobel Committee for Chemistry for 19 years in various roles: as an ordinary member, chairman, and, most recently, as secretary. He completed his tenure three years ago upon reaching the age limit of 70 for participation on the Nobel Committee.

The professor was an invited speaker at the Twin4Promis workshop entitled “Folding and Misfolding of Soluble and Integral Membrane Proteins” and this was his first interview with Greek media. Naturally, the conversation begins with the Nobel Prize.

How Nobel Laureates Are Selected

I inquire about the weight of having a ‘key voice’ in selecting Nobel laureates. “I wouldn’t call it a ‘heavy’ duty, but it certainly requires a lot of time. Committee members meet monthly throughout the year and have extensive work reading and writing reports in between,” he explains. He then describes the selection process:

“It’s a cyclical process beginning each fall when the Committee sends out 3,000-4,000 invitations to scientists, including previous laureates and scientific bodies worldwide, asking them to nominate candidates for the next year’s prize by February 1st. By late spring, the Committee, aided by experts, reviews the proposals to narrow down the list to four, five, or six top choices. This task is often quite challenging. In the summer, a final discussion occurs, followed by a vote and a report draft. The Committee, composed of seven to nine members, meets again at the end of summer to review the report and make a final recommendation to the Royal Swedish Academy of Sciences. During the first week of October, the Academy’s plenary session convenes behind closed doors, votes on the prize, and announces it within the next hour.”

There are five Nobel committees, one for each prize. The committees for physics, chemistry, and economics are based at the Royal Swedish Academy of Sciences, the committee for physiology or medicine is at the Karolinska Institute, and the literature committee is at the Swedish Academy. The peace prize committee, located in Oslo, operates under a different regime. Notably, the archive of candidate lists, nominations, and reports remains secret for 50 years.

For outsiders, the process might seem magical, but for committee members, it becomes a routine—albeit a special one. I wonder if there was ever a moment he felt a scientist was unjustly overlooked. “There are always comments post-award, questioning why it went to one person over another, but the procedure has been followed precisely for the past 50 years. It would be a significant oversight if the Committee missed a major contribution entirely. Fortunately, that never happened during my tenure.”

There Is No Life Without Membranes

One of Professor von Heijne’s primary research goals is to understand membrane proteins, which constitute a third of all proteins in a cell. In 2008, he received the prestigious Advanced Grant from the European Research Council to study how membrane proteins fold into their final three-dimensional structures.

“Without proteins in the membrane, the cell would be unprotected and isolated, as these proteins facilitate communication with the environment, intake of nutrients, and secretion of substances,” explains von Heijne. He likens these proteins to ‘gates’ for the exchange of information and nutrients.

He adds that the origin of self-replicating systems and membranes remains a topic of inquiry: whether self-replicating systems existed before being enclosed in membranes or whether membranes created conditions for these systems to function. “What’s certain is that life as we know it wouldn’t exist without membranes” he notes.

A Close ‘Encounter’ with Membrane Proteins

Von Heijne’s interest in membrane proteins began by chance during his Ph.D. He saw a cartoon in a French scientific magazine depicting a protein chain interacting with a cell membrane, sparking his fascination.

Combining theoretical and experimental methods, von Heijne has developed software for predicting “signal peptides” of proteins, which guide newly synthesized proteins to their secretion sites in the membrane. His predictive models continue to be validated in laboratories today. “We now have the tools to predict not only signal peptides but the entire three-dimensional structure of proteins,” he says.

His research has implications for identifying pharmaceutical targets and studying medically significant membrane proteins. His work has underscored the crucial role of positively charged amino acids in determining membrane protein topology, led to new methods for predicting transmembrane segments, and illuminated many aspects of membrane protein assembly in both prokaryotic and eukaryotic cells.

Lost in… Co-Translational Protein Folding

Proteins, composed of long chains of amino acids, are synthesized in ribosomes. The sequence of amino acids is determined by DNA. Misfolding of these proteins can lead to diseases such as Alzheimer’s, Parkinson’s, and certain cancers.

For the past fifty years, researchers have sought to understand what controls protein folding. Among them is Professor von Heijne, who now focuses solely on experimental studies. In his lecture on “Co-translational Protein Folding,” he described how newly synthesized proteins begin to fold within the ribosome’s exit tunnel, contrary to the long-held belief that folding starts only once the protein is outside the tunnel. “We are discovering that protein folding occurs simultaneously with translation,” von Heijne explains. He studies where and when proteins fold as they exit or remain within the ribosome. This process also applies to integral membrane proteins, which von Heijne investigates. He examines the mechanisms of transmembrane channels involved in the movement of newly synthesized proteins across cellular membranes.

The Twin4Promis project, titled “Twinning for Excellence in Research, Training, and Innovation in Protein Misfolding Diseases,” coordinated by the National Hellenic Research Foundation, is privileged to have Professor von Heijne as a member of the Scientific Advisory Board. We are grateful for his invaluable contribution and insightful lecture at the 1st Twin4Promis Training Workshop.

For more details from the interview conducted by Vasso Michopoulou, please click here (in Greek).

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