Transformational Work Over a Career: Breakthrough Prize in Life Sciences for PLOS Authors

How do you measure lifetime achievement? It’s not by assessing individual works but by consideration and evaluation of consistent contributions to a discipline over time. Contributions may be independently substantial, but in science, a researcher’s impact is more often made through gradual insights that accrue meaning as a discipline advances. Over the course of a career, creative thinkers and leaders in science can significantly influence a field, and humanity more broadly.

A recently established award provides one measure of lifetime achievement for life sciences—the Breakthrough Prize. Established in 2013, the Breakthrough Prize in Life Sciences honors “transformative advances toward understanding living systems and extending human life.” The prize encourages celebration and recognition of “outstanding minds.” Those scientists who “think big, take risks and have made a significant impact on our lives” each receive $3 million for their work that provides fundamental and far-reaching understanding of biological mechanisms.

The Breakthrough Prize in Life Sciences is designed to bring public attention, financial reward and a bit of glamor to outstanding scientists who over the course of their careers have changed the way scientists think about basic principles. Through a central component of the award, the impact of honored scientists’ work is extended to a broader general audience. Recipients are invited to present public talks – with recorded lectures made available to the public – “allowing everyone to keep abreast of the latest developments in life sciences, guided by contemporary masters of the field,” according to the Breakthrough Prize website. Breakthrough Prizes are also awarded in fundamental physics and mathematics.

This year, five scientists received life sciences prizes; collectively these creative thinkers have published 30 papers in PLOS journals (13 in PLOS Biology, 16 in PLOS ONE and one in PLOS Genetics), providing their work to the global community free of access and reuse restrictions. The 2018 Breakthrough Prizes in Life Sciences were awarded to:

• Joanne Chory, for pioneering work elucidating mechanisms by which plants “optimize their growth, development, and cellular structure to transform sunlight into chemical energy.” Chory has published work with PLOS on how the circadian clock coordinates plant growth through synchronized gene expression, on growth patterning in the model plant system Arabidopsis and a novel approach to identify required gene regulatory elements, and on diurnal and clock-regulated transcription factors and their target cis-regulatory elements in additional plant models. The Chory team first published with PLOS in 2004.

• Kim Nasmyth, for elucidating the “sophisticated mechanism that mediates the perilous separation of duplicated chromosomes during cell division and thereby prevents genetic diseases such as cancer.” Nasmyth’s work in PLOS Biology covers the influence of excess heterochromatin (highly packed DNA) segments and cohesin protein accumulation on sister chromatid separation, and that the protein shugoshin protects centromeres until chromosomes are ready to separate. He and colleagues from the Research Institute of Molecular Pathology, in Vienna, Austria, first published with PLOS in 2005.

• Don Cleveland, for characterizing molecular mechanisms involved in the pathogenesis of inherited Amyotrophic Lateral Sclerosis (ALS), “including the role of glia in neurodegeneration, and for establishing antisense oligonucleotide therapy in animal models of ALS and Huntington disease.” Cleveland’s work using post-mortem human tissue samples and transgenic mice showed that mRNA oxidation is an early event associated with motor neuron deterioration in ALS, and possibly other neurological diseases. His work on the enzyme superoxide dismutase, responsible for breaking down toxic, charged oxygen molecules known as superoxide radicals, included assessing the therapeutic effect of human fetal spinal neural stem cells grafted into the lumbar spine of transgenic rats presymptomatic for ALS. Cleveland and his many colleagues first published with PLOS (twice) in 2008.

Two scientists, Kazutoshi Mori of Kyoto University, Japan, and Peter Walter of the University of California, San Francisco, received Breakthrough Prizes for their independent work on “elucidating the unfolded protein response, a cellular quality-control system that detects disease-causing unfolded proteins and directs cells to take corrective measures.” The unfolded protein response (UPR) is a phylogenetically conserved endoplasmic reticulum-to-nucleus signaling pathway that senses unfolded proteins early on in the biosynthetic process, and then transmits that information to the cell nucleus. This information stimulates a genetic transcription program designed to re-establish cellular homeostasis by increasing the intracellular machinery and processes that help proteins fold.

• Various cellular insults, writes Mori in his team’s PLOS Biology article, “including exposure to pharmacological agents that perturb protein folding, genetic mutation of ER chaperones or chaperone substrates, viral infection, metabolic demands, and even normal differentiation and function of professional secretory cells” impact the UPR in similar and unique ways. His earlier work published with PLOS examined the differential influence of low-level, severe and chronic stress on UPR activation. More recently, Mori has extended his investigations to the development of a high-throughput screening assay that incorporates a molecular biosensor to identify small molecule activators of the endoplasmic reticulum stress response in malignant glioma cells.

• Since 2004, Walter has published 12 papers with PLOS covering the role of endoplasmic reticulum expansion in the UPR in yeast; a teasing out of the relationship between cell proliferation, cell death and protein folding in human embryonic kidney cell lines; and the importance of targeting a key transcription factor to the cell membrane, to provide the appropriate cellular response to protein folding status in bacteria. Walter’s first two papers published in PLOS Biology, presented as a series together with a Synopsis, described amplitude adjustment signals for the UPR in yeast. Prior to this work, the UPR was thought to largely be a binary, on or off, function.

Perhaps more than other prize recipients, Joanne Chory was surprised by her inclusion as an awardee, explaining to the San Diego Union-Tribune, “this prize has been more associated with biomedical things.” The award may be a nod to the relevance of Chory’s current work to climate change. Those interested in the connection between mechanisms of sunlight and clock-regulated plant development to global warming may find of interest the Ecological Impacts of Climate Change Collection and newly launched Responding to Climate Change Channel.

International lifetime achievement awards are given in many fields, including economics, music and physical sciences, among others. With support of founding sponsors Mark Zuckerberg, Priscilla Chan, Sergey Brin, Anne Wojcicki and Yuri Milner, life sciences has another prize of its own, with a musical perk. This year’s awardees were honored at a gala hosted by Morgan Freeman with a performance of “See You Again” by Wiz Khalifa and Nana Ou-Yang.

Hero image credit: breakthroughprize.org