Impactful science

A Nobel prize-winning American cell biologist talks about extracellular vesicles (EVs), exciting developments in the field and the challenges facing scientific publishing.

American cell biologist Randy Wayne Schekman’s fascination with microbiology started at the age of 12 with a toy microscope.Over 50 years later, Schekman, a Professor of molecular and cell biology at the University of California, Berkeley, received the Nobel Prize in Physiology or Medicine for the discoveries of machinery regulating vesicle traffic, a major transport system in our cells. He will be in Sydney to deliver the ASBMB Grimwade Keynote Plenary Lecture at this year’s ComBio2018 conference to be held 23–26 September at the International Convention Centre, Sydney.

Schekman’s research efforts have been focused on extracellular vesicles (EVs), which are produced by essentially all eukaryotic cells and have been shown to convey proteins, small molecule metabolites and small RNA molecules to target cells where they are taken up by endocytosis. “Once internalised, the vesicle constituents may alter the metabolism and pattern of gene expression in the target cell. My lab has devised a biochemical method to evaluate the RNA molecules that are packaged into a particular class of EVs, exosomes, and have developed a cell-free reaction that recapitulates the sorting of selected species of microRNAs that form in an incubation containing membranes and cytosol from broken cultured human cells.”

Separately, Schekman has also served as the Editor-in-Chief of two international scientific journals — The Proceedings of the National Academy of Sciences, and for the past 7+ years, the life science journal eLife.

He’s also Chair of an initiative on Parkinson’s disease (https://parkinsonsroadmap.org/). This initiative will grow into an organisation to support research on basic disease mechanisms responsible for Parkinson’s disease with the financial backing of the Sergey Brin Family Foundation.

At the upcoming ComBio conference, Schekman will talk about his team’s work on how small RNA molecules are sorted into vesicles secreted by human cells. “We have discovered the role of two RNA binding proteins and two different RNA sequences that promote high fidelity sorting of microRNA molecules.”

The field of biomedical science is going through an exciting phase. Commenting on three developments that stand out, Schekman said, “The ability to visualise molecules in real time by super-resolution microscopy, the ability to modify specific target genes by genome editing and the ability to unleash the power of T-cells to attack tumours.” These three revolutionary developments have allowed us to see and control molecules with unprecedented precision and in the case of T-cells, to cure/control certain tumours that used to be invariably fatal.

While there are opportunities, there are also challenges. “We have never had greater power to explore the natural world and yet the understanding and acceptance of science and the scientific method is routinely attacked by ill-informed critics who place faith, dogma and politics ahead of reason. Our politicians too often embrace populism and prejudice ahead of progress on such vital issues as climate change, enhancement of food resources by the application of modern technologies such as genetic engineering and genome editing, and the international exchange of scholars around the world. Scientists must take a more active role in public education and appreciation of science and all that it has provided.”

Schekman has long been an open advocate of open access. When asked about tackling the issue of perverse incentives, he said, “The Open Access (OA) movement, launched in Britain but greatly expanded by the Public Library of Science (PLoS), seeks to eliminate the firewall that separates published work from public access.  OA journals are funded by a mix of page charges and philanthropic or foundation support.  Most OA journals embrace a more liberal licensing agreement on the use and re-use of published work, favouring the creative commons licence rather than a copyright held by the publisher. Some publishers, particularly commercial firms, view the OA movement as a threat to the viability of their business plan. Major commercial publishers, particularly Elsevier, have fought against government mandates for OA publication of publicly funded research.”

The assessment of scholarly achievement depends critically on the proper evaluation and publication of research work in scholarly journals, he said. “Investigators face a dizzying array of journal styles that include commercial, not-for-profit and academic society journals that are supported by a mix of subscription and page charges. The most selective and successful journals, Science, Nature and Cell (a life science journal owned by Elsevier), maintain a firm hold on the high end of the scientific literature by appealing to investigators to submit only their most important work. Typically, these journals publish only a small fraction of the papers they receive and for the most part they rely on professional editors rather than active scholars to make key editorial decisions.

“In the past, publishers such as Nature and Elsevier reinforced their high standing by relying on a metric, the journal impact factor (JIF) that computes the average number of citations of papers published in the journal during the preceding two-year period. As a consequence, many investigators, who quite naturally seek career advancement, strive to publish in these journals even at the expense of repeated cycles of review, wasteful additional experimental work and ultimately lost time. A growing number of investigators feel it is time for scholars to reassume authority for the publication of their research work and to eschew the use of JIF in the evaluation of scholarly achievement and favour OA publications over what I have called the ‘luxury’ journals.”

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