Plant Science Decadal Vision 2020–2030: Reimagining the Potential of Plants for a Healthy and Sustainable Future

Plants, and the biological systems around them, are key to the future health of the planet and its inhabitants. The Plant Science Decadal Vision 2020–2030 frames our ability to perform vital and far‐reaching research in plant systems sciences, essential to how we value participants and apply emerging technologies. We outline a comprehensive vision for addressing some of our most pressing global problems through discovery, practical applications, and education. The Decadal Vision was developed by the participants at the Plant Summit 2019, a community event organized by the Plant Science Research Network. The Decadal Vision describes a holistic vision for the next decade of plant science that blends recommendations for research, people, and technology. Going beyond discoveries and applications, we, the plant science community, must implement bold, innovative changes to research cultures and training paradigms in this era of automation, virtualization, and the looming shadow of climate change. Our vision and hopes for the next decade are encapsulated in the phrase reimagining the potential of plants for a healthy and sustainable future. The Decadal Vision recognizes the vital intersection of human and scientific elements and demands an integrated implementation of strategies for research (Goals 1–4), people (Goals 5 and 6), and technology (Goals 7 and 8). This report is intended to help inspire and guide the research community, scientific societies, federal funding agencies, private philanthropies, corporations, educators, entrepreneurs, and early career researchers over the next 10 years. The research encompass experimental and computational approaches to understanding and predicting ecosystem behavior; novel production systems for food, feed, and fiber with greater crop diversity, efficiency, productivity, and resilience that improve ecosystem health; approaches to realize the potential for advances in nutrition, discovery and engineering of plant‐based medicines, and green infrastructure. Launching the Transparent Plant will use experimental and computational approaches to break down the phytobiome into a parts store that supports tinkering and supports query, prediction, and rapid‐response problem solving. Equity, diversity, and inclusion are indispensable cornerstones of realizing our vision. We make recommendations around funding and systems that support customized professional development. Plant systems are frequently taken for granted therefore we make recommendations to improve plant awareness and community science programs to increase understanding of scientific research. We prioritize emerging technologies, focusing on non‐invasive imaging, sensors, and plug‐and‐play portable lab technologies, coupled with enabling computational advances. Plant systems science will benefit from data management and future advances in automation, machine learning, natural language processing, and artificial intelligence‐assisted data integration, pattern identification, and decision making. Implementation of this vision will transform plant systems science and ripple outwards through society and across the globe. Beyond deepening our biological understanding, we envision entirely new applications. We further anticipate a wave of diversification of plant systems practitioners while stimulating community engagement, underpinning increasing entrepreneurship. This surge of engagement and knowledge will help satisfy and stoke people\u27s natural curiosity about the future, and their desire to prepare for it, as they seek fuller information about food, health, climate and ecological systems

Correction: First-In-Class Small Molecule ONC201 Induces DR5 and Cell Death in Tumor but Not Normal Cells to Provide a Wide Therapeutic Index as an Anti-Cancer Agent.

We previously identified ONC201 (TIC10) as a first-in-class orally active small molecule with robust antitumor activity that is currently in clinical trials in advanced cancers. Here, we further investigate the safety characteristics of ONC201 in preclinical models that reveal an excellent safety profile at doses that exceed efficacious doses by 10-fold. In vitro studies indicated a strikingly different dose-response relationship when comparing tumor and normal cells where maximal effects are much stronger in tumor cells than in normal cells. In further support of a wide therapeutic index, investigation of tumor and normal cell responses under identical conditions demonstrated large apoptotic effects in tumor cells and modest anti-proliferative effects in normal cells that were non-apoptotic and reversible. Probing the underlying mechanism of apoptosis indicated that ONC201 does not induce DR5 in normal cells under conditions that induce DR5 in tumor cells; DR5 is a pro-apoptotic TRAIL receptor previously linked to the anti-tumor mechanism of ONC201. GLP toxicology studies in Sprague-Dawley rats and beagle dogs at therapeutic and exaggerated doses revealed no dose-limiting toxicities. Observations in both species at the highest doses were mild and reversible at doses above 10-fold the expected therapeutic dose. The no observed adverse event level (NOAEL) was ≥42 mg/kg in dogs and ≥125 mg/kg in rats, which both correspond to a human dose of approximately 1.25 g assuming standard allometric scaling. These results provided the rationale for the 125 mg starting dose in dose escalation clinical trials that began in 2015 in patients with advanced cancer

Cohorts used in GLP toxicology studies with ONC201.

<p>Human equivalent doses are estimated by standard allometric scaling and assumes a 60kg human body weight.</p><p>* Indicates the dose determined to be the NOAEL is shaded gray for each species.</p><p>Cohorts used in GLP toxicology studies with ONC201.</p

Effect of ONC201 on surface TRAIL and DR5 In tumor and normal cells.

<p>(A) Surface TRAIL and DR5 expression in HCT116 (tumor) and HFF (normal) cells following treatment with ONC201 (5 μM, 72 hr, n = 3). IgG was included as an isotype negative control. Doxorubicin (Doxo) is shown as a positive control (1 μg/mL). (B) Surface TRAIL and DR5 in normal fibroblasts following treatment with ONC201 (5 μM) or doxorubicin (1 μg/mL, 72 hr, n = 3). Values (y-axis) is expressed as mean fluorescence intensity.</p

ONC201 effects on proliferation and cell death in tumor and normal cells.

<p>(A) Cell viability assays following ONC201 treatment at indicated concentrations for 72 hours (n = 3). Doxorubicin (Doxo) was used at 1 μg/mL as a positive control in normal fibroblasts. (B) Cell cycle analysis of tumor and normal cells following treatment with ONC201 (5 μM) or doxorubicin (Doxo, 1μg/mL) for 72 hours (n = 3). (C) Cell viability assay in MRC5 cells following a 72 hour treatment with ONC201 (5 μM) or DMSO and the indicated recovery period in complete drug-free media after this treatment (n = 3). Time points are given as time following removal on ONC201 after 72 hour treatment. (D) Cell viability of tumor and normal cells following treatment with ONC201 (5 μM, n = 3) for 72 hours.</p