Biological sciences: Determining phenotype from genotype

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The NSF’s Division of Integrative Organismal Systems, within the Directorate for Biological Sciences, discusses how their work determining phenotype from genotype is fighting food insecurity

In a recent National Academies of Science and Medicine proceedings report entitled “Next Steps for Functional Genomics,” Division Director for the Division of Integrative Organismal Systems, Donal Manahan, was quoted as saying the ability to predict the phenotype of a cell or an organism from what we know about its genome and its environment may be viewed as the biggest gap in biological knowledge. That gap is closing – bringing us closer to the ability to harness that knowledge for use in biotechnology to support the bioeconomy – thanks to years of research supported by the Division and more broadly, by NSF’s Directorate for Biological Sciences.

Understanding the Rules of Life Support for uncovering the genotype to phenotype relationship runs across the Directorate and the various areas within the biological sciences. It also cuts across the entire agency through the Understanding the Rules of Life program, one of NSF’s 10 Big Ideas, which is stewarded by the Directorate. The program seeks to elucidate the rules that predict an organism’s observable characteristics, its phenotype, including those determined by its genetic makeup.

Other programs, including the Plant Genome Research Program (PGRP), Enabling Discovery through Genomic Tools (EDGE), and IMAGiNE: Integrating Mechanisms of Adaptation with Genes in Networks and across Environments, support specific areas of research within this broader field and the development and dissemination of tools and data to enable further research.

Deciphering and decoding the plant genome

For nearly 23 years, PGRP has supported research to uncover the genetic code in all manner of plants and, through its TRTech-PGR Track, to develop innovative tools to assist in that investigation. In coordination with federal agencies as part of the U.S. National Plant Genome Initiative, the program has successfully enforced a mandate for rapid dissemination of data and resources that has democratised functional genomics across the scientific community, providing for comparisons across species and collaborations between research teams. Throughout its history, PRGP has aided in decoding the genomes of crop plants – such as maize, wheat, soybean, tomatoes, rice, and cotton – and non-crop plants as well. These efforts have expanded our understanding of functional genomics and laid the groundwork for advancements in biotechnology and advanced agriculture, including new ways to limit the impact of agriculture on climate, creation of more robust and resilient crop plants or production of synthetic cells that could open up new avenues for biomanufacturing and biofuels.

Building on PGRP and expanding reach Throughout its history, PGRP has spurred NSF programs that have engaged several partners, all of which have provided new insights, tools, and data to help understand the phenotype from genotype relationship and expand our knowledge and the application of functional genomics.

From 2009 through 2015, the Directorate managed the Basic Research to Enable Agricultural Development (BREAD) program in partnership with the Bill and Melinda Gates Foundation. BREAD supported research that addressed the constraints to smallholder agriculture in the developing world. This research included the development of phenotyping tools and devices and sequence and functional genomics resources to enable proof-of-concept basic research addressing drought, pests, disease, and other serious problems in crop plants important for subsistence farming in developing countries. The research supported has implications  for the development of heartier crops important to large-scale agriculture as well.

Since 2016, the Enabling Discovery through GEnomic Tools (EDGE) program has helped develop innovative tools, technologies, resources, and infrastructure that have advanced biological research focused on the identification of the causal mechanisms connecting genes and phenotypes in plants, animals and microbes. In 2020, this division-initiated program expanded to become directorate-wide, supporting both tool development and hypothesis-driven functional genomic research across all scales. Current EDGE-supported research could enable genetic editing of milkweed to enhance its medicinal properties and, separately, seeks to create a “toolkit” for identifying the genes that allow certain plants to thrive in stressful environments that could aid in the creation of elite crop cultivars to help meet global agricultural needs.

Predicting phenotype from genotype in context

Building upon the success of these programs, the Directorate and the Division announced their intention to support interdisciplinary research on how genomes, phenomesand the environment interact to give rise to complex traits such as behaviour, development, morphology, and physiology in diverse organisms through Integrating Mechanisms of Adaptation with Genes in Networks and across Environments (IMAGiNE). Advances in sequencing technologies, the generation of tools and genetic resources as well as an abundance of existing large-scale genomics datasets with NSF support provide unique opportunities to address the underlying mechanisms governing organism-environment interactions that are central to organismal function across time and space. Only through these studies can we begin to explore how to manipulate genomes and phenomes to address national needs and promote the bioeconomy.

Current funding opportunities

In addition to PGRP, EDGE, and IMAGINE, the Directorate also has opportunities available for research into Plant Synthetic Biology and Plant Biotic Interactions. Submissions to opportunities under these programs can be made at any time as these programs do not have deadlines for proposals. The Directorate also continues to evaluate how it can best support innovative research, the creation and dissemination of data and tools, and the development of resources and infrastructure in the broad plant research and functional genomic areas of research.

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