The Lasker Awards recognize the contributions of scientists, physicians and public servants who have made major advances in the understanding, diagnosis, treatment and prevention of human disease. Each year since 1945, dedicated scientists benefit from the mission of the Albert and Mary Lasker Foundation to recognize research excellence, public education and advocacy.
As a champion of biomedical research, Mary Lasker worked to increase public appreciation for and government funding of medical sciences. As a result of her advocacy efforts, several NIH Institutes were newly created, including the National Heart Institute, the National Institute of Mental Health and the (originally named) National Institute of Neurological Diseases and Blindness. Lasker helped change the biomedical research landscape in the United States and the scientific community to this day benefits from her dedication.
PLOS is proud that six of this year’s seven Lasker awardees have published research or an interview with PLOS, and we are fortunate to benefit from the expertise of Charles M. Rice of The Rockefeller University in his role as an Academic Editor for PLOS Pathogens.
Here are the 2016 Lasker Award honorees with a summary of their PLOS research and interviews, spanning five journals and The PLOS Blog Network, for a collective total of 38 articles and two interviews.
Oxygen sensing—an essential process for survival:
Gregg L. Semenza’s three PLOS ONE articles cover the role of NADPH oxidase in Hypoxia Inducible Factor-1α (HIF-1α) activation, the dependency on tumor suppressor p53 for macrophage migration inhibitory factor’s effect on HIF-1 activation, and the ability of HIF-1α to regulate the expression of cell adhesion molecule CD44.
Peter J. Ratcliffe published two PLOS ONE articles and one each in PLOS Biology and PLOS Medicine. Some of this work examines the relationship between the von Hippel-Lindau (VHL) tumor suppressor gene, HIF-1 and extracellular matrix in C. elegans, the role of VHL-HIF pathway in human cardiopulmonary physiology and function at standard and high altitudes, and most recently the investigation of compounds that inhibit the hypoxia sensors of the HIF system, the HIF prolyl-hydroxylases, with implications for therapeutic treatment of stroke or other diseases of cerebral ischemia.
William G. Kaelin’s PLOS Biology article – published in the journal’s inaugural year – explores the relationship between inactivation of the VHL gene, subsequent HIF2α activity and renal carcinoma tumor formation.
Hepatitis C replicon system and drug development:
Charles M. Rice has eight articles with PLOS; three in PLOS ONE and five with PLOS Pathogens. His virology research – while primarily focused on hepatitis C virus (HCV) – also addresses arthropod-transmitted viruses in the Flaviviridae family, such as yellow fever virus, and natural inhibitors of HIV identified from simulation screening of the pan-African Natural Product Library followed by cell-based testing. A subset of Rice’s HCV work published in PLOS Pathogens covers direct deregulation of the cell cycle in HCV infection as a contributor to liver disease, host cell protein and lipid mapping to uncover temporal and global changes as a result of HCV infection and a mutational structural analysis of the p7 protein revealing positions important for particle assembly and infectivity.
Ralf Bartenschlager tops the PLOS list with 27 articles; 20 in PLOS Pathogens and seven in PLOS ONE. Select key early work on HCV includes the role of cyclophilin A in HCV replication and polyprotein processing, the role of HCV p7 protein as a membrane pore involved in production and release of infectious virions and the dependence of HCV envelope glycoprotein secretion on assembly of triglyceride rich lipoproteins.
Bartenschlager’s team also determined the nonstructural protein 5A (NS5A), a component of the viral RNA replication machinery, as a key factor for the formation of infectious HCV particles through an assembly determinant domain and lipid droplets. Bartenschlager’s seminal microscopy work on the intracellular membranes of HCV infected cells is visually stunning and included in the PLOS Pathogens 10th Anniversary Collection.
More recent articles describe use of a yeast two-hybrid screening strategy to generate an interactome of cellular proteins that may function with influenza virus non-structural proteins NS1 and NS2, potentially informing therapeutic interventions, and work on Dengue virus that provides a genetic map of determinants involved in viral RNA replication and extends the list of functions ascribed to the enigmatic nonstructural protein 1.
Discoveries in DNA replication and leadership in science and education:
In 2012, PLOS Genetics’ Jane Gitschier Interviews turned to this year’s Lasker-Koshland Special Achievement Award in Medical Science awardee Bruce Alberts for his memories of how he got into science and his thoughts on learning from failure and getting committees to reach consensus. More recently Alberts shared with PLOS his insights into issues facing scientists today, such as journal impact factors, new forms of recognition for contributions to the scientific publication process and the role of senior as well as junior researchers in changing the culture of science.
For those wanting more information on the significance of the work of this year’s winners and the award in general, The Lasker Foundation and Cell provide coverage. Cell has also curated Collections dedicated to Hypoxia-Inducible Factors and virus infections. Much, but not all, of the content is Open Access.
Image credit: The Lasker Foundation