Popularly known as the “Oscars of Science,” the 2023 Breakthrough Prize awardees were announced yesterday. The prize recognizes scientists who have made game-changing discoveries in life sciences, fundamental physics, and mathematics. Each prize is $3 million.

The awards in the life sciences category this year went to Clifford Brangwynne and Anthony Hyman for their discovery of a new cellular mechanism of organization, Demis Hassabis and John Jumper for developing an AI system that accurately predicts the structure of proteins, and Emmanuel Mignot and Masashi Yanagisawa for their discovery of the molecular cause of narcolepsy.

“Neurodegenerative disease breakthroughs, AI solving protein structure, and more…” said business magnate Sergey Brin who is a co-founder and sponsor of the Breakthrough Prize Foundation, “are incredible advances that deserve to be celebrated.”

A new mechanism of cellular organization

Until now the interior of a cell was envisioned as a membranous sac packed with randomly interacting molecules with membranous organelles responsible for specialized activities. Pioneering work in the laboratories of Anthony Hyman, PhD, head of the Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG), and a co-founder of Dewpoint Therapeutics; and Clifford Brangwynne, PhD, professor of chemical and biological engineering, director of the Princeton Bioengineering Initiative, and a co-founder of Nereid Therapeutics, discovered a new cellular mechanism based in the role biomolecular condensates in cellular communication and organization. They received one of the three Breakthrough Prizes in the life sciences.

In addition to the localization of cellular activity in membrane-bound organelles, Hyman and Brangwynne discovered a new physical principle that concentrates interactions between proteins and other biomolecules within cells, in the absence of membrane enclosures. These transient crucibles of biological reactions in cells consist of dynamic liquid droplets that form rapidly and spontaneously by phase separation, like droplets of oil in water. Hyman, Brangwynne, and others have shown that these liquid condensates play a role in cellular processes such as signal transduction, cell division, the assembly of nucleoli in the cell nucleus, and the regulation of chromatin. Ongoing research based on these novel findings may lead to clinical applications in neurodegenerative diseases such as amyotrophic lateral sclerosis and Alzheimer’s disease.

Cause of a sleep disorder  

Although all animals sleep, science is just beginning to uncover its mysteries, biological necessity, the cause of dreams, and the transition between sleep and waking states. Narcolepsy, a rare chronic neurological sleep disorder that disrupts sleep-wake cycles, causing patients to sleep excessively or suddenly fall asleep amid activity, offers a clue into the mysterious mechanisms of sleep.

Research in the laboratories of Emmanuel Mignot, PhD, director of the Center for Sleep Sciences at Stanford University School of Medicine and Masashi Yanagisawa, PhD, professor at the University of Tsukuba, converged to discover that the loss of the protein orexin (also called hypocretin) causes narcolepsy in both animals and humans. In dogs, narcolepsy is caused by a mutation in the neural receptor that binds orexin, while in humans, the immune system mistakenly attacks cells that produce orexin to trigger narcolepsy.

Based on these findings, drugs that stimulate orexin receptors and reverse symptoms in narcolepsy in patients have been developed, in addition to drugs designed to induce sleep. Mignot and Yanagisawa’s work revealed that narcolepsy is a neurodegenerative disease with autoimmune origins. The findings uncover a basic mechanism of the sleep-wakefulness cycle and add to the growing body of evidence that selective loss of neurons underlie neurodegenerative diseases.

Predicting protein structures

One of the biggest roadblocks in biology has been the prediction of the three-dimensional structure of functional proteins from sequence data. Accurately predicting the structure of proteins, the workhorses of cells, is key to understanding basic biological mechanisms and developing targeted therapeutics. The development of the AI system AlphaFold2 by DeepMind marked a paradigm-shift in structural biology by predicting a protein’s 3D structure from its amino acid sequence with a high level of accuracy. Demis Hassabis, PhD, CEO and co-founder of DeepMind, a subsidiary of Alphabet, and John Jumper, PhD, senior scientist at DeepMind are the leaders behind the development of the AI system. With their team at DeepMind, Hassabis and Jumper conceived and constructed the deep learning system that is now freely available to scientists.

Since its development two years ago, AlphaFold2 has already revolutionized life sciences. It has predicted the structures of 200 million proteins from across the tree of life that are now available in a public database. The program reduces the time spent determining protein structure from months or years to hours or minutes. AlphaFold2 is benefiting drug design, vaccine development, synthetic biology, nanotechnology, and the understanding of basic biology.

Beyond the main prizes, six New Horizons Prizes, each of $100,000, were distributed among 11 early-career scientists and mathematicians who have already made a substantial impact on their fields. In addition, three Maryam Mirzakhani New Frontiers Prizes, of $50,000 each, were awarded to women mathematicians who have recently completed their PhDs and produced important results.

Past Breakthrough Prize winners in each field comprise the selection committees. Founded by Sergey Brin, Priscilla Chan, Mark Zuckerberg, Julia and Yuri Milner, and Anne Wojcicki, the Breakthrough Prizes have been sponsored by foundations established by them for the past eleven years.

Chan Zuckerberg Initiative co-founders and co-CEOs Priscilla Chan and Mark Zuckerberg said, “These laureates and early-career scientists are pushing the boundaries of what’s possible in research and science, and we’re thrilled to honor their accomplishments.”